Scholars@Duke
Anatoli I. Yashin

Anatoli I. Yashin

Research Professor in the Social Science Research Institute
Social Science Research Institute
aiy@duke.edu
Duke Box 90420, Durham, NC 27708-0408
2024 W. Main Street, Durham, NC 27705
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Selected Publications

Whole genome-wide sequence analysis of long-lived families (Long-Life Family Study) identifies MTUS2 gene associated with late-onset Alzheimer's disease.

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · April 2024 IntroductionLate-onset Alzheimer's disease (LOAD) has a strong genetic component. Participants in Long-Life Family Study (LLFS) exhibit delayed onset of dementia, offering a unique opportunity to investigate LOAD genetics.MethodsWe conduc ... Full text Cite

Assessing tilavonemab efficacy in early Alzheimer's disease via longitudinal item response theory modeling.

Journal Article Alzheimers Dement (N Y) · 2024 INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by declines in cognitive and functional severities. This research utilized the Clinical Dementia Rating (CDR) to assess the influence of tilavonemab on these deterioration ... Full text Open Access Link to item Cite

A comparison of genetic imputation methods using Long Life Family Study genotypes and sequence data with the 1000 Genome reference panel

Journal Article International Journal of Bioinformatics Research and Applications · January 1, 2020 This study compares methods of imputing genetic markers, given a typed GWAS scaffold from the Long Life Family Study (LLFS) and latest reference panel of 1000-Genomes. We examined two programs for pre-phasing haplotypes MACH/SHAPEIT2 and MINIMAC/IMPUTE2 fo ... Full text Cite

A forecasting model of disease prevalence based on the McKendrick-von Foerster equation.

Journal Article Math Biosci · May 2019 A new model for disease prevalence based on the analytical solutions of McKendric-von Foerster's partial differential equations is developed. Derivation of the model and methods to cross check obtained results are explicitly demonstrated. Obtained equation ... Full text Link to item Cite

Study of the bivariate survival data using frailty models based on Lévy processes

Journal Article AStA Advances in Statistical Analysis · March 1, 2019 Frailty models allow us to take into account the non-observable inhomogeneity of individual hazard functions. Although models with time-independent frailty have been intensively studied over the last decades and a wide range of applications in survival ana ... Full text Cite

Genetics of Human Longevity From Incomplete Data: New Findings From the Long Life Family Study.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · October 2018 The special design of the Long Life Family Study provides a unique opportunity to investigate the genetics of human longevity by analyzing data on exceptional lifespans in families. In this article, we performed two series of genome wide association studie ... Full text Cite

Time trends in the prevalence of cancer and non-cancer diseases among older U.S. adults: Medicare-based analysis.

Journal Article Exp Gerontol · September 2018 Longer lifespan is accompanied by a larger number of chronic diseases among older adults. Because of a growing proportion of older adults in the U.S., this brings the problem of age-related morbidity to the forefront as a major contributor to rising medica ... Full text Link to item Cite

Impact of demography and population dynamics on the genetic architecture of human longevity.

Journal Article Aging · August 2018 The study of the genetics of longevity has been mainly addressed by GWASs that considered subjects from different populations to reach higher statistical power. The "price to pay" is that population-specific evolutionary histories and trade-offs were negle ... Full text Cite

Causal effects of cardiovascular risk factors on onset of major age-related diseases: A time-to-event Mendelian randomization study.

Journal Article Experimental gerontology · July 2018 BackgroundsElucidating the causal effects of common intermediate risk factors on the onset of age-related diseases is indispensable for developing prevention and intervention procedures.MethodsWe conducted two-stage time-to-event Mendelia ... Full text Cite

Hidden heterogeneity in Alzheimer's disease: Insights from genetic association studies and other analyses.

Journal Article Experimental gerontology · July 2018 Despite evident success in clarifying many important features of Alzheimer's disease (AD) the efficient methods of its prevention and treatment are not yet available. The reasons are likely to be the fact that AD is a multifactorial and heterogeneous healt ... Full text Cite

Identifying the causes of the changes in the prevalence patterns of diabetes in older U.S. adults: A new trend partitioning approach.

Journal Article J Diabetes Complications · April 2018 AIMS: To identify how efforts to control the diabetes epidemic and the resulting changes in diabetes mellitus, type II (T2D) incidence and survival have affected the time-trend of T2D prevalence. METHODS: A newly developed method of trend decomposition was ... Full text Link to item Cite

Mortality and Macrovascular Risk in Elderly With Hypertension and Diabetes: Effect of Intensive Drug Therapy.

Journal Article Am J Hypertens · January 12, 2018 BACKGROUND: This study identifies the effect of intensive drug therapy (IDT) in individuals age 65+ with diabetes (type 2 diabetes mellitus (T2D)) and hypertension on all-cause death, congestive heart failure (CHF), hospitalization for myocardial infarctio ... Full text Link to item Cite

Time Trends in the Prevalence of Neurocognitive Disorders and Cognitive Impairment in the United States: The Effects of Disease Severity and Improved Ascertainment.

Journal Article J Alzheimers Dis · 2018 BACKGROUND: Trends in the prevalence of cognitive impairment (CI) based on cognitive assessment instruments are often inconsistent with those of neurocognitive disorders (ND) based on Medicare claims records. OBJECTIVE: We hypothesized that improved ascert ... Full text Link to item Cite

A genetic stochastic process model for genome-wide joint analysis of biomarker dynamics and disease susceptibility with longitudinal data.

Journal Article Genetic epidemiology · November 2017 Unraveling the underlying biological mechanisms or pathways behind the effects of genetic variations on complex diseases remains one of the major challenges in the post-GWAS (where GWAS is genome-wide association study) era. To further explore the relation ... Full text Cite

rqt: an R package for gene-level meta-analysis.

Journal Article Bioinformatics (Oxford, England) · October 2017 MotivationDespite recent advances of modern GWAS methods, it is still remains an important problem of addressing calculation an effect size and corresponding p-value for the whole gene rather than for single variant.ResultsWe developed an ... Full text Cite

Theory of partitioning of disease prevalence and mortality in observational data.

Journal Article Theor Popul Biol · April 2017 In this study, we present a new theory of partitioning of disease prevalence and incidence-based mortality and demonstrate how this theory practically works for analyses of Medicare data. In the theory, the prevalence of a disease and incidence-based morta ... Full text Open Access Link to item Cite

Telomeres and the natural lifespan limit in humans.

Journal Article Aging · April 2017 An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics ... Full text Open Access Cite

Uncoupling associations of risk alleles with endophenotypes and phenotypes: insights from the ApoB locus and heart-related traits.

Journal Article Aging cell · February 2017 Traditionally, genomewide association studies (GWAS) have emphasized the benefits of large samples in the analyses of age-related traits rather than their specific properties. We adopted a realistic concept of genetic susceptibility to inherently heterogen ... Full text Open Access Cite

stpm: an R package for stochastic process model.

Journal Article BMC bioinformatics · February 2017 BackgroundThe Stochastic Process Model (SPM) represents a general framework for modeling the joint evolution of repeatedly measured variables and time-to-event outcomes observed in longitudinal studies, i.e., SPM relates the stochastic dynamics of ... Full text Open Access Cite

The Survival of Spouses Marrying Into Longevity-Enriched Families.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · January 2017 BackgroundStudies of longevity-enriched families are an important tool to gain insight into the mechanisms of exceptionally long and healthy lives. In the Long Life Family Study, the spouses of the members of the longevity-enriched families are of ... Full text Open Access Cite

Whole genome-wide sequence analysis of long-lived families (Long-Life Family Study) identifies MTUS2 gene associated with late-onset Alzheimer's disease.

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · April 2024 IntroductionLate-onset Alzheimer's disease (LOAD) has a strong genetic component. Participants in Long-Life Family Study (LLFS) exhibit delayed onset of dementia, offering a unique opportunity to investigate LOAD genetics.MethodsWe conduc ... Full text Cite

Assessing tilavonemab efficacy in early Alzheimer's disease via longitudinal item response theory modeling.

Journal Article Alzheimers Dement (N Y) · 2024 INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by declines in cognitive and functional severities. This research utilized the Clinical Dementia Rating (CDR) to assess the influence of tilavonemab on these deterioration ... Full text Open Access Link to item Cite

A comparison of genetic imputation methods using Long Life Family Study genotypes and sequence data with the 1000 Genome reference panel

Journal Article International Journal of Bioinformatics Research and Applications · January 1, 2020 This study compares methods of imputing genetic markers, given a typed GWAS scaffold from the Long Life Family Study (LLFS) and latest reference panel of 1000-Genomes. We examined two programs for pre-phasing haplotypes MACH/SHAPEIT2 and MINIMAC/IMPUTE2 fo ... Full text Cite

A forecasting model of disease prevalence based on the McKendrick-von Foerster equation.

Journal Article Math Biosci · May 2019 A new model for disease prevalence based on the analytical solutions of McKendric-von Foerster's partial differential equations is developed. Derivation of the model and methods to cross check obtained results are explicitly demonstrated. Obtained equation ... Full text Link to item Cite

Study of the bivariate survival data using frailty models based on Lévy processes

Journal Article AStA Advances in Statistical Analysis · March 1, 2019 Frailty models allow us to take into account the non-observable inhomogeneity of individual hazard functions. Although models with time-independent frailty have been intensively studied over the last decades and a wide range of applications in survival ana ... Full text Cite

Genetics of Human Longevity From Incomplete Data: New Findings From the Long Life Family Study.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · October 2018 The special design of the Long Life Family Study provides a unique opportunity to investigate the genetics of human longevity by analyzing data on exceptional lifespans in families. In this article, we performed two series of genome wide association studie ... Full text Cite

Time trends in the prevalence of cancer and non-cancer diseases among older U.S. adults: Medicare-based analysis.

Journal Article Exp Gerontol · September 2018 Longer lifespan is accompanied by a larger number of chronic diseases among older adults. Because of a growing proportion of older adults in the U.S., this brings the problem of age-related morbidity to the forefront as a major contributor to rising medica ... Full text Link to item Cite

Impact of demography and population dynamics on the genetic architecture of human longevity.

Journal Article Aging · August 2018 The study of the genetics of longevity has been mainly addressed by GWASs that considered subjects from different populations to reach higher statistical power. The "price to pay" is that population-specific evolutionary histories and trade-offs were negle ... Full text Cite

Causal effects of cardiovascular risk factors on onset of major age-related diseases: A time-to-event Mendelian randomization study.

Journal Article Experimental gerontology · July 2018 BackgroundsElucidating the causal effects of common intermediate risk factors on the onset of age-related diseases is indispensable for developing prevention and intervention procedures.MethodsWe conducted two-stage time-to-event Mendelia ... Full text Cite

Hidden heterogeneity in Alzheimer's disease: Insights from genetic association studies and other analyses.

Journal Article Experimental gerontology · July 2018 Despite evident success in clarifying many important features of Alzheimer's disease (AD) the efficient methods of its prevention and treatment are not yet available. The reasons are likely to be the fact that AD is a multifactorial and heterogeneous healt ... Full text Cite

Identifying the causes of the changes in the prevalence patterns of diabetes in older U.S. adults: A new trend partitioning approach.

Journal Article J Diabetes Complications · April 2018 AIMS: To identify how efforts to control the diabetes epidemic and the resulting changes in diabetes mellitus, type II (T2D) incidence and survival have affected the time-trend of T2D prevalence. METHODS: A newly developed method of trend decomposition was ... Full text Link to item Cite

Mortality and Macrovascular Risk in Elderly With Hypertension and Diabetes: Effect of Intensive Drug Therapy.

Journal Article Am J Hypertens · January 12, 2018 BACKGROUND: This study identifies the effect of intensive drug therapy (IDT) in individuals age 65+ with diabetes (type 2 diabetes mellitus (T2D)) and hypertension on all-cause death, congestive heart failure (CHF), hospitalization for myocardial infarctio ... Full text Link to item Cite

Time Trends in the Prevalence of Neurocognitive Disorders and Cognitive Impairment in the United States: The Effects of Disease Severity and Improved Ascertainment.

Journal Article J Alzheimers Dis · 2018 BACKGROUND: Trends in the prevalence of cognitive impairment (CI) based on cognitive assessment instruments are often inconsistent with those of neurocognitive disorders (ND) based on Medicare claims records. OBJECTIVE: We hypothesized that improved ascert ... Full text Link to item Cite

A genetic stochastic process model for genome-wide joint analysis of biomarker dynamics and disease susceptibility with longitudinal data.

Journal Article Genetic epidemiology · November 2017 Unraveling the underlying biological mechanisms or pathways behind the effects of genetic variations on complex diseases remains one of the major challenges in the post-GWAS (where GWAS is genome-wide association study) era. To further explore the relation ... Full text Cite

rqt: an R package for gene-level meta-analysis.

Journal Article Bioinformatics (Oxford, England) · October 2017 MotivationDespite recent advances of modern GWAS methods, it is still remains an important problem of addressing calculation an effect size and corresponding p-value for the whole gene rather than for single variant.ResultsWe developed an ... Full text Cite

Theory of partitioning of disease prevalence and mortality in observational data.

Journal Article Theor Popul Biol · April 2017 In this study, we present a new theory of partitioning of disease prevalence and incidence-based mortality and demonstrate how this theory practically works for analyses of Medicare data. In the theory, the prevalence of a disease and incidence-based morta ... Full text Open Access Link to item Cite

Telomeres and the natural lifespan limit in humans.

Journal Article Aging · April 2017 An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics ... Full text Open Access Cite

Uncoupling associations of risk alleles with endophenotypes and phenotypes: insights from the ApoB locus and heart-related traits.

Journal Article Aging cell · February 2017 Traditionally, genomewide association studies (GWAS) have emphasized the benefits of large samples in the analyses of age-related traits rather than their specific properties. We adopted a realistic concept of genetic susceptibility to inherently heterogen ... Full text Open Access Cite

stpm: an R package for stochastic process model.

Journal Article BMC bioinformatics · February 2017 BackgroundThe Stochastic Process Model (SPM) represents a general framework for modeling the joint evolution of repeatedly measured variables and time-to-event outcomes observed in longitudinal studies, i.e., SPM relates the stochastic dynamics of ... Full text Open Access Cite

The Survival of Spouses Marrying Into Longevity-Enriched Families.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · January 2017 BackgroundStudies of longevity-enriched families are an important tool to gain insight into the mechanisms of exceptionally long and healthy lives. In the Long Life Family Study, the spouses of the members of the longevity-enriched families are of ... Full text Open Access Cite

haploR: an R package for querying web-based annotation tools.

Journal Article F1000Research · January 2017 We developed haploR, an R package for querying web based genome annotation tools HaploReg and RegulomeDB. haploR gathers information in a data frame which is suitable for downstream bioinformatic analyses. This will facilitate post-genome wid ... Full text Cite

cophesim: a comprehensive phenotype simulator for testing novel association methods.

Journal Article F1000Research · January 2017 Simulation is important in evaluating novel methods when input data is not easily obtainable or specific assumptions are needed. We present cophesim, a software to add the phenotype to generated genotype data prepared with a genetic simulator. The o ... Full text Cite

Modeling of immunosenescence and risk of death from respiratory infections: Evaluation of the role of antigenic load and population heterogeneity

Journal Article Mathematical Modelling of Natural Phenomena · January 1, 2017 It is well known that efficacy of immune functions declines with age. It results in an increase of severity and duration of respiratory infections and also in dramatic growth of risk of death due to these diseases after age 65. The goal of this work is to ... Full text Cite

Corrigendum: Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases.

Journal Article Frontiers in genetics · January 2017 [This corrects the article on p. 179 in vol. 7, PMID: 27790247.]. ... Full text Cite

Resilience Versus Robustness in Aging.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · November 2016 Full text Open Access Cite

Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study.

Journal Article Biogerontology · November 2016 The apolipoprotein E (apoE) is a classic example of a gene exhibiting pleiotropism. We examine potential pleiotropic associations of the apoE2 allele in three biodemographic cohorts of long-living individuals, offspring, and spouses from the Long Life Fami ... Full text Open Access Cite

Pleiotropic Associations of Allelic Variants in a 2q22 Region with Risks of Major Human Diseases and Mortality.

Journal Article PLoS genetics · November 2016 Gaining insights into genetic predisposition to age-related diseases and lifespan is a challenging task complicated by the elusive role of evolution in these phenotypes. To gain more insights, we combined methods of genome-wide and candidate-gene studies. ... Full text Cite

Circulatory Diseases and Aging

Chapter · October 6, 2016 Age patterns of incidence rates of major circulatory diseases (CDs), their time trends, risk factors, and other characteristics capable of contributing to the debates on the role of aging in the deterioration of human health are investigated using standard ... Full text Cite

Multidimensional Stochastic Process Model and its applications to analysis of longitudinal data with genetic information

Journal Article ACM-BCB 2016 - 7th ACM Conference on Bioinformatics, Computational Biology, and Health Informatics · October 2, 2016 Stochastic Process Model has many applications in analysis of longitudinal biodemographic data. In general, such data contain various physiological variables (sometimes known as covariates or physiological indices). Longitudinal data can also contain genet ... Full text Open Access Cite

Explicating heterogeneity of complex traits has strong potential for improving GWAS efficiency.

Journal Article Scientific reports · October 2016 Common strategy of genome-wide association studies (GWAS) relying on large samples faces difficulties, which raise concerns that GWAS have exhausted their potential, particularly for complex traits. Here, we examine the efficiency of the traditional sample ... Full text Open Access Cite

Interaction Between the FOXO1A-209 Genotype and Tea Drinking Is Significantly Associated with Reduced Mortality at Advanced Ages.

Journal Article Rejuvenation Res · June 2016 On the basis of the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are signific ... Full text Open Access Link to item Cite

Dynamics of biomarkers in relation to aging and mortality.

Journal Article Mechanisms of ageing and development · June 2016 Contemporary longitudinal studies collect repeated measurements of biomarkers allowing one to analyze their dynamics in relation to mortality, morbidity, or other health-related outcomes. Rich and diverse data collected in such studies provide opportunitie ... Full text Open Access Cite

Resistance to stresses and reliability of biological systems: Insights for genetic studies of human aging, health, and longevity

Conference Proceedings - 2nd International Symposium on Stochastic Models in Reliability Engineering, Life Science, and Operations Management, SMRLO 2016 · March 11, 2016 Connection between stress resistance and longevity in biological organisms is widely discussed and confirmed experimentally. Much less is known about the roles of genetic and non-genetic factors in regulation of such connection. Earlier studies emphasized ... Full text Open Access Cite

Novel loci and pathways significantly associated with longevity.

Journal Article Sci Rep · February 25, 2016 Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a gen ... Full text Open Access Link to item Cite

Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro-longevity variants.

Journal Article Biogerontology · February 2016 Complex diseases are major contributors to human mortality in old age. Paradoxically, many genetic variants that have been associated with increased risks of such diseases are found in genomes of long-lived people, and do not seem to compromise longevity. ... Full text Open Access Cite

How the effects of aging and stresses of life are integrated in mortality rates: insights for genetic studies of human health and longevity.

Journal Article Biogerontology · February 2016 Increasing proportions of elderly individuals in developed countries combined with substantial increases in related medical expenditures make the improvement of the health of the elderly a high priority today. If the process of aging by individuals is a ma ... Full text Open Access Cite

Optimal Versus Realized Trajectories of Physiological Dysregulation in Aging and Their Relation to Sex-Specific Mortality Risk.

Journal Article Frontiers in public health · January 2016 While longitudinal changes in biomarker levels and their impact on health have been characterized for individual markers, little is known about how overall marker profiles may change during aging and affect mortality risk. We implemented the recently devel ... Full text Open Access Cite

How Genes Modulate Patterns of Aging-Related Changes on the Way to 100: Biodemographic Models and Methods in Genetic Analyses of Longitudinal Data.

Journal Article North American actuarial journal : NAAJ · January 2016 Background and objectiveTo clarify mechanisms of genetic regulation of human aging and longevity traits, a number of genome-wide association studies (GWAS) of these traits have been performed. However, the results of these analyses did not meet ex ... Full text Open Access Cite

Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases.

Journal Article Frontiers in genetics · January 2016 Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through cert ... Full text Open Access Cite

Pure and Confounded Effects of Causal SNPs on Longevity: Insights for Proper Interpretation of Research Findings in GWAS of Populations with Different Genetic Structures.

Journal Article Frontiers in genetics · January 2016 This paper shows that the effects of causal SNPs on lifespan, estimated through GWAS, may be confounded and the genetic structure of the study population may be responsible for this effect. Simulation experiments show that levels of linkage disequilibrium ... Full text Open Access Cite

Coordinated Action of Biological Processes during Embryogenesis Can Cause Genome-Wide Linkage Disequilibrium in the Human Genome and Influence Age-Related Phenotypes.

Journal Article Annals of gerontology and geriatric research · January 2016 A role of non-Mendelian inheritance in genetics of complex, age-related traits is becoming increasingly recognized. Recently, we reported on two inheritable clusters of SNPs in extensive genome-wide linkage disequilibrium (LD) in the Framingham Heart Study ... Open Access Cite

Introduction: The Biodemography of Complex Relationships Among Aging, Health, and Longevity

Chapter · January 1, 2016 The growth in interest in the biodemography of human aging, health, and longevity is motivated by the desire to better understand the factors and mechanisms responsible for age patterns and time trends in human mortality rates and survival curves. The avai ... Full text Cite

Conclusions Regarding Empirical Patterns of Aging, Health, and Longevity

Chapter · January 1, 2016 Age is a major risk factor for phenotypes characterizing human health, well-being, and survival in late life. The risks of these phenotypes expressed in forms of pathological dysregulation of physiological functions, incidence or prevalence of diseases, ca ... Full text Cite

Conclusions Regarding Statistical Modeling of Aging, Health, and Longevity

Chapter · January 1, 2016 The analyses conducted in Part I did not exhaust all factors affecting age patterns of age-related changes in health and mortality. They actually provided a strong rationale for conducting more detailed analyses which require advanced methods of mathematic ... Full text Cite

Approaches to Statistical Analysis of Longitudinal Data on Aging, Health, and Longevity: Biodemographic Perspectives

Chapter · January 1, 2016 Longitudinal data play a pivotal role in discovering different aspects of knowledge related to aging, health, and longevity. There are many statistical methods for the analysis of longitudinal data, which is one of the most prolific areas of statistical sc ... Full text Cite

Continuing the Search for Determinants of Healthy Life Span and Longevity

Chapter · January 1, 2016 Life expectancy in humans worldwide has been experiencing dramatic increases for the past two centuries (Oeppen and Vaupel 2002). In most countries, the extension of lifespan is associated with a transition from a long historical period of high fertility a ... Full text Cite

Dynamic Characteristics of Aging-Related Changes as Predictors of Longevity and Healthy Lifespan

Chapter · January 1, 2016 It is well known from epidemiological research that values of indices describing physiological states at a given age may influence human morbidity and mortality risks. Studies of the connections between aging and life span suggest that the dynamic properti ... Full text Cite

The Complex Role of Genes in Diseases and Traits in Late Life: An Example of the Apolipoprotein E Polymorphism

Chapter · January 1, 2016 Decades of studies of candidate genes show that they are not linked to aging-related traits in a straightforward manner. Recent genome-wide association studies (GWAS) have reached fundamentally the same conclusion by showing that traits in late life are li ... Full text Cite

The Latent Class Stochastic Process Model for Evaluation of Hidden Heterogeneity in Longitudinal Data

Chapter · January 1, 2016 Various approaches to statistical model building and data analysis that incorporate unobserved heterogeneity are ubiquitous in different scientific disciplines. Frailty models introduce the concept of unobserved or hidden heterogeneity in survival analysis ... Full text Cite

Stochastic Process Models of Mortality and Aging

Chapter · January 1, 2016 A better understanding of relationships among human aging, health, and longevity requires integrative statistical methods capable of taking into account relevant knowledge accumulated in the field when extracting useful information from the data. In this c ... Full text Cite

Indices of Cumulative Deficits

Chapter · January 1, 2016 Despite broad interest in the mechanisms responsible for human aging and numerous efforts to identify factors contributing to morbidity, biological senescence, and longevity, these processes still remain elusive. This makes the systemic description of agin ... Full text Cite

Evidence for Dependence Among Diseases

Chapter · January 1, 2016 Demographic calculations evaluating the role of chronic diseases in life expectancy use the assumption that diseases are independent. Disease independence was a plausible hypothesis in the era of infectious diseases. However, the health problems of modern ... Full text Cite

Age Trajectories of Physiological Indices: Which Factors Influence Them?

Chapter · January 1, 2016 Longitudinal data on aging, health, and longevity provide researchers with a unique opportunity to observe aging-related changes in biomarkers that describe the functioning of individual organisms during people’s life courses. In this chapter, empirical es ... Full text Cite

How Biodemographic Approaches Can Improve Statistical Power in Genetic Analyses of Longitudinal Data on Aging, Health, and Longevity

Chapter · January 1, 2016 The modern era of revolutionary advances in genetics provides great opportunities and challenges for the field of biodemography. We discuss approaches to work with the rich data available in modern longitudinal studies of aging, health, and longevity that ... Full text Cite

Integrative Mortality Models for the Study of Aging, Health, and Longevity: Benefits of Combining Data

Chapter · January 1, 2016 In a number of longitudinal studies, individual health and physiological/biological variables are repeatedly measured for a relatively large number of study subjects. Such data have good potential for evaluating properties of dynamic mechanisms involved in ... Full text Cite

Linear Latent Structure Analysis: Modeling High-Dimensional Survey Data

Chapter · January 1, 2016 The formulation of the recently developed Linear Latent Structures (LLS) analysis, its statistical properties, the algorithm for parameter estimation and its implementation, simulation studies, and application of LLS model to the National Long Term Care Su ... Full text Cite

Integrative Mortality Models with Parameters That Have Biological Interpretations

Chapter · January 1, 2016 Mortality rates are important characteristics of life span distributions that integrate the influences of many external and internal factors affecting individuals in the population during their life course. These include the ontogenetic program, individual ... Full text Cite

TIME TRENDS OF DISEASE PREVALENCE AMONG OLDER U.S. ADULTS

Conference The Gerontologist · November 2015 Full text Cite

Quantification of biological aging in young adults.

Journal Article Proc Natl Acad Sci U S A · July 28, 2015 Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human ... Full text Open Access Link to item Cite

GxE interactions between FOXO genotypes and drinking tea are significantly associated with prevention of cognitive decline in advanced age in China.

Journal Article J Gerontol A Biol Sci Med Sci · April 2015 Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with ... Full text Open Access Link to item Cite

Trade-offs in the effects of the apolipoprotein E polymorphism on risks of diseases of the heart, cancer, and neurodegenerative disorders: insights on mechanisms from the Long Life Family Study.

Journal Article Rejuvenation research · April 2015 The lack of evolutionary established mechanisms linking genes to age-related traits makes the problem of genetic susceptibility to health span inherently complex. One complicating factor is genetic trade-off. Here we focused on long-living participants of ... Full text Open Access Cite

Cardiovascular comorbidities and survival of lung cancer patients: Medicare data based analysis.

Journal Article Lung Cancer · April 2015 OBJECTIVES: To evaluate the role of cardiovascular disease (CVD) comorbidity in survival of patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The impact of seven CVDs (at the time of NSCLC diagnosis and during subsequent follow-up) o ... Full text Open Access Link to item Cite

Mortality, Biodemography of

Chapter · March 26, 2015 The biodemography of mortality aims to explain observed age patterns and time trends in mortality rates from the biological point of view. It integrates knowledge about biological factors and mechanisms affecting mortality rates with demographic informatio ... Full text Cite

Genetics of aging, health, and survival: dynamic regulation of human longevity related traits.

Journal Article Frontiers in genetics · January 2015 BackgroundThe roles of genetic factors in human longevity would be better understood if one can use more efficient methods in genetic analyses and investigate pleiotropic effects of genetic variants on aging and health related traits.Data and ... Full text Open Access Cite

Birth Cohort, Age, and Sex Strongly Modulate Effects of Lipid Risk Alleles Identified in Genome-Wide Association Studies.

Journal Article PloS one · January 2015 Insights into genetic origin of diseases and related traits could substantially impact strategies for improving human health. The results of genome-wide association studies (GWAS) are often positioned as discoveries of unconditional risk alleles of complex ... Full text Open Access Cite

Aging and health--a systems biology perspective. Introduction.

Journal Article Interdisciplinary topics in gerontology · January 2015 Open Access Cite

Introduction

Chapter · October 9, 2014 Cite

Aging and health - A systems biology perspective

Book · October 9, 2014 Aging is a major risk factor for chronic diseases, which in turn can provide information about the aging of a biological system. This publication serves as an introduction to systems biology and its application to biological aging. Key pathways and process ... Full text Cite

Age, gender, and cancer but not neurodegenerative and cardiovascular diseases strongly modulate systemic effect of the Apolipoprotein E4 allele on lifespan.

Journal Article PLoS genetics · January 2014 Enduring interest in the Apolipoprotein E (ApoE) polymorphism is ensured by its evolutionary-driven uniqueness in humans and its prominent role in geriatrics and gerontology. We use large samples of longitudinally followed populations from the Framingham H ... Full text Open Access Cite

Introduction

Chapter · January 1, 2014 Cite

Age, Gender, and Cancer but Not Neurodegenerative and Cardiovascular Diseases Strongly Modulate Systemic Effect of the Apolipoprotein E4 Allele on Lifespan

Journal Article PLoS Genetics · January 1, 2014 Enduring interest in the Apolipoprotein E (ApoE) polymorphism is ensured by its evolutionary-driven uniqueness in humans and its prominent role in geriatrics and gerontology. We use large samples of longitudinally followed populations from the Framingham H ... Full text Cite

Joint Analyses of Longitudinal and Time-to-Event Data in Research on Aging: Implications for Predicting Health and Survival.

Journal Article Frontiers in public health · January 2014 Longitudinal data on aging, health, and longevity provide a wealth of information to investigate different aspects of the processes of aging and development of diseases leading to death. Statistical methods aimed at analyses of time-to-event data jointly w ... Full text Open Access Cite

Biodemographic Analyses of Longitudinal Data on Aging, Health, and Longevity: Recent Advances and Future Perspectives.

Journal Article Advances in geriatrics · January 2014 Biodemography became one of the most innovative and fastest growing areas in demography. This progress is fueled by the growing variability and amount of relevant data available for analyses as well as by methodological developments allowing for addressing ... Full text Open Access Cite

Genetic Structures of Population Cohorts Change with Increasing Age: Implications for Genetic Analyses of Human aging and Life Span.

Journal Article Annals of gerontology and geriatric research · January 2014 BackgroundCorrecting for the potential effects of population stratification is an important issue in genome wide association studies (GWAS) of complex traits. Principal component analysis (PCA) of the genetic structure of the population under stud ... Open Access Cite

ON IDENTIFIABILITY OF MIXTURES OF INDEPENDENT DISTRIBUTION LAWS, .

Journal Article ESAIM. Probability and statistics = Probabilites et statistique : P & S · January 2014 We consider representations of a joint distribution law of a family of categorical random variables (i.e., a multivariate categorical variable) as a mixture of independent distribution laws (i.e. distribution laws according to which random va ... Full text Open Access Cite

A new algorithm for predicting time to disease endpoints in Alzheimer's disease patients.

Journal Article Journal of Alzheimer's disease : JAD · January 2014 BackgroundThe ability to predict the length of time to death and institutionalization has strong implications for Alzheimer's disease patients and caregivers, health policy, economics, and the design of intervention studies.ObjectiveTo de ... Full text Open Access Cite

Morbidity risks among older adults with pre-existing age-related diseases.

Journal Article Exp Gerontol · December 2013 Multi-morbidity is common among older adults; however, for many aging-related diseases there is no information for U.S. elderly population on how earlier-manifested disease affects the risk of another disease manifested later during patient's lifetime. Qua ... Full text Open Access Link to item Cite

Recovery and survival from aging-associated diseases.

Journal Article Exp Gerontol · August 2013 OBJECTIVES: Considering disease incidence to be a main contributor to healthy lifespan of the US elderly population may lead to erroneous conclusions when recovery/long-term remission factors are underestimated. Using two Medicare-based population datasets ... Full text Open Access Link to item Cite

Time trends of incidence of age-associated diseases in the US elderly population: Medicare-based analysis.

Journal Article Age Ageing · July 2013 OBJECTIVES: time trends of age-adjusted incidence rates of 19 ageing-related diseases were evaluated for 1992-2005 period with the National Long Term Care Survey and the Surveillance, Epidemiology and End RESULTS Registry data both linked to Medicare data ... Full text Open Access Link to item Cite

Circulatory Diseases in the U.S. Elderly in the Linked National Long-Term Care Survey-Medicare Database: Population-Based Analysis of Incidence, Comorbidity, and Disability.

Journal Article Res Aging · July 2013 Incidence rates of acute coronary heart disease (ACHD; including myocardial infarction and angina pectoris), stroke, and heart failure (HF) were studied for their age, disability, and comorbidity patterns in the U.S. elderly population using the National L ... Full text Open Access Link to item Cite

Biogenetic mechanisms predisposing to complex phenotypes in parents may function differently in their children.

Journal Article J Gerontol A Biol Sci Med Sci · July 2013 This study focuses on the participants of the Long Life Family Study to elucidate whether biogenetic mechanisms underlying relationships among heritable complex phenotypes in parents function in the same way for the same phenotypes in their children. Our r ... Full text Open Access Link to item Cite

Inter-chromosomal level of genome organization and longevity-related phenotypes in humans.

Journal Article Age (Dordrecht, Netherlands) · April 2013 Studies focusing on unraveling the genetic origin of health span in humans assume that polygenic, aging-related phenotypes are inherited through Mendelian mechanisms of inheritance of individual genes. We use the Framingham Heart Study (FHS) data to examin ... Full text Open Access Cite

The role of lipid-related genes, aging-related processes, and environment in healthspan.

Journal Article Aging cell · April 2013 The inherent complexity of aging-related traits can temper progress in unraveling the genetic origins of healthspan. We focus on two generations in the Framingham Heart Study, the original (FHS) and offspring (FHSO) cohorts, to determine whether aging-rela ... Full text Open Access Cite

Trade-off in the effect of the APOE gene on the ages at onset of cardiocascular disease and cancer across ages, gender, and human generations.

Journal Article Rejuvenation research · February 2013 Decades of studies of candidate genes show their complex role in aging-related traits. We focus on apolipoprotein E e2/3/4 polymorphism and ages at onset of cardiovascular diseases (CVD) and cancer in the parental and offspring generations of the Framingha ... Full text Open Access Cite

Methodological aspects of studying human aging, health, and mortality

Chapter · January 1, 2013 Age trajectories of mortality rates in human populations characterize individuals’ inequality in the duration of life. Various models of mortality rates are used in the analyses of survival data in demographic and epidemiological applications aiming to ide ... Full text Cite

How lifespan associated genes modulate aging changes: lessons from analysis of longitudinal data.

Journal Article Frontiers in genetics · January 2013 Background and objectiveThe influence of genes on human lifespan is mediated by biological processes that characterize body's functioning. The age trajectories of these processes contain important information about mechanisms linking aging, health ... Full text Open Access Cite

Patterns of Aging-Related changes on the way to 100: An Approach to studying aging, mortality, and longevity from longitudinal data

Journal Article North American Actuarial Journal · December 1, 2012 The objective of this paper is to investigate dynamic properties of age trajectories of physiological indices and their effects on mortality risk and longevity using longitudinal data on more than 5,000 individuals collected in biennial examinations of the ... Full text Open Access Cite

The Role of Genes and Life Course in Late Life Diseases

Conference GENETIC EPIDEMIOLOGY · November 1, 2012 Link to item Cite

GENES, HEALTH, AGING, AND ENVIRONMENT: HOW ARE THEY RELATED?

Journal Article GERONTOLOGIST · November 1, 2012 Link to item Cite

How genes influence life span: the biodemography of human survival.

Journal Article Rejuvenation research · August 2012 BackgroundIn genome-wide association studies (GWAS) of human life span, none of the genetic variants has reached the level of genome-wide statistical significance. The roles of such variants in life span regulation remain unclear.Data and meth ... Full text Open Access Cite

Polygenic effects of common single-nucleotide polymorphisms on life span: when association meets causality.

Journal Article Rejuvenation research · August 2012 Recently we have shown that the human life span is influenced jointly by many common single-nucleotide polymorphisms (SNPs), each with a small individual effect. Here we investigate further the polygenic influence on life span and discuss its possible biol ... Full text Open Access Cite

Increase in circulating levels of IGF-1 and IGF-1/IGFBP-3 molar ratio over a decade is associated with colorectal adenomatous polyps.

Journal Article Int J Cancer · July 15, 2012 High levels of circulating insulin-like growth factor-1 (IGF-1) have been associated with increased risk of several cancers. Regarding colorectal cancer, these associations are generally weak. We hypothesized that an increase in IGF-1 over time would be a ... Full text Open Access Link to item Cite

Modeling longitudinal data on health aging and life span

Journal Article Physics of Life Reviews · June 1, 2012 We address comments from the three discussants of our paper, paying particular attention to the properties of our model likely to be of interest in new applications to complex dynamic systems. © 2012 Elsevier B.V. ... Full text Open Access Cite

The quadratic hazard model for analyzing longitudinal data on aging, health, and the life span.

Journal Article Physics of life reviews · June 2012 A better understanding of processes and mechanisms linking human aging with changes in health status and survival requires methods capable of analyzing new data that take into account knowledge about these processes accumulated in the field. In this paper, ... Full text Open Access Cite

New stochastic carcinogenesis model with covariates: an approach involving intracellular barrier mechanisms.

Journal Article Math Biosci · March 2012 In this paper we present a new multiple-pathway stochastic model of carcinogenesis with potential of predicting individual incidence risks on the basis of biomedical measurements. The model incorporates the concept of intracellular barrier mechanisms in wh ... Full text Open Access Link to item Cite

Age patterns of incidence of geriatric disease in the U.S. elderly population: Medicare-based analysis.

Journal Article J Am Geriatr Soc · February 2012 OBJECTIVES: To use the Medicare Files of Service Use (MFSU) to evaluate patterns in the incidence of aging-related diseases in the U.S. elderly population. DESIGN: Age-specific incidence rates of 19 aging-related diseases were evaluated using the National ... Full text Open Access Link to item Cite

An age-structured extension to the vectorial capacity model.

Journal Article PloS one · January 2012 BackgroundVectorial capacity and the basic reproductive number (R(0)) have been instrumental in structuring thinking about vector-borne pathogen transmission and how best to prevent the diseases they cause. One of the more important simplifying as ... Full text Open Access Cite

Effect of the APOE Polymorphism and Age Trajectories of Physiological Variables on Mortality: Application of Genetic Stochastic Process Model of Aging.

Journal Article Scientifica · January 2012 We evaluated effects of the APOE polymorphism (carriers versus noncarriers of the e4 allele) and age trajectories of total cholesterol (CH) and diastolic blood pressure (DBP) on mortality risk in the Framingham Heart Study (original cohort). We found that ... Full text Open Access Cite

Joint analysis of health histories, physiological state, and survival

Journal Article Mathematical Population Studies · December 1, 2011 Data on individual health histories, age trajectories of physiological or biological variables, and mortality allow for the study of the joint evolution of health and physiological states and their effects on mortality. Individual health and physiological ... Full text Open Access Cite

Trade-off in the effects of the apolipoprotein E polymorphism on the ages at onset of CVD and cancer influences human lifespan.

Journal Article Aging cell · June 2011 Progress in unraveling the genetic origins of healthy aging is tempered, in part, by a lack of replication of effects, which is often considered a signature of false-positive findings. We convincingly demonstrate that the lack of genetic effects on an agin ... Full text Open Access Cite

Modeling hematopoietic system response caused by chronic exposure to ionizing radiation.

Journal Article Radiation and environmental biophysics · May 2011 A new model of the hematopoietic system response in humans chronically exposed to ionizing radiation describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the four blood cell types (lymphocytes, neutrophiles, ... Full text Open Access Cite

Leukocyte telomere length, breast cancer risk in the offspring: the relations with father's age at birth.

Journal Article Mechanisms of ageing and development · April 2011 Recent studies have reported that leukocyte telomere length (LTL) is longer in offspring of older fathers. Longer telomeres might increase cancer risk. We examined the relation of father's age at the birth of the offspring (FAB) with LTL in the offspring i ... Full text Open Access Cite

Do gender, disability, and morbidity affect aging rate in the LLFS? Application of indices of cumulative deficits.

Journal Article Mechanisms of ageing and development · April 2011 We used an approach of cumulative deficits to evaluate the rate of aging in 4954 participants of the Long-Life Family Study (LLFS) recruited in the U.S. (Boston, New York, and Pittsburgh) and Denmark. We used an array of 85 health-related deficits covering ... Full text Open Access Cite

Evaluation of genotype-specific survival using joint analysis of genetic and non-genetic subsamples of longitudinal data.

Journal Article Biogerontology · April 2011 Small sample size of genetic data is often a limiting factor for desirable accuracy of estimated genetic effects on age-specific risks and survival. Longitudinal non-genetic data containing information on survival or disease onsets of study participants fo ... Full text Open Access Cite

Age trajectories of physiological indices in relation to healthy life course.

Journal Article Mechanisms of ageing and development · March 2011 We analysed relationship between the risk of onset of "unhealthy life" (defined as the onset of cancer, cardiovascular diseases, or diabetes) and longitudinal changes in body mass index, diastolic blood pressure, hematocrit, pulse pressure, pulse rate, and ... Full text Open Access Cite

Health and function of participants in the Long Life Family Study: A comparison with other cohorts.

Journal Article Aging · January 2011 Individuals from families recruited for the Long Life Family Study (LLFS) (n= 4559) were examined and compared to individuals from other cohorts to determine whether the recruitment targeting longevity resulted in a cohort of individuals with better health ... Full text Open Access Cite

Medical cost trajectories and onsets of cancer and noncancer diseases in US elderly population.

Journal Article Comput Math Methods Med · 2011 Time trajectories of medical costs-associated with onset of twelve aging-related cancer and chronic noncancer diseases were analyzed using the National Long-Term Care Survey data linked to Medicare Service Use files. A special procedure for selecting indiv ... Full text Open Access Link to item Cite

Heritability estimates of endophenotypes of long and health life: the Long Life Family Study.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · December 2010 BackgroundIdentification of gene variants that contribute to exceptional survival may provide critical biologic information that informs optimal health across the life span.MethodsAs part of phenotype development efforts for the Long Life ... Full text Open Access Cite

Estimation and validation of a multiattribute model of Alzheimer disease progression.

Journal Article Medical decision making : an international journal of the Society for Medical Decision Making · November 2010 ObjectivesTo estimate and validate a multiattribute model of the clinical course of Alzheimer disease (AD) from mild AD to death in a high-quality prospective cohort study, and to estimate the impact of hypothetical modifications to AD progression ... Full text Open Access Cite

Joint influence of small-effect genetic variants on human longevity.

Journal Article Aging · September 2010 The results of genome-wide association studies of complex traits, such as life span or age at onset of chronic disease, suggest that such traits are typically affected by a large number of small-effect alleles. Individually such alleles have little predict ... Full text Open Access Cite

Early hematopoietic effects of chronic radiation exposure in humans.

Journal Article Health physics · September 2010 The major goal of this study is to investigate and quantitatively describe the nature of the relationship between the characteristics of chronic exposure to ionizing radiation and specific patterns of hematopoiesis reduction. The study is based on about 3, ... Full text Open Access Cite

Modeling deterministic effects in hematopoietic system caused by chronic exposure to ionizing radiation in large human cohorts.

Journal Article Health physics · September 2010 A new model of the hematopoietic system for humans chronically exposed to ionizing radiation allows for quantitative description of the initial hematopoiesis inhibition and subsequent increase in the risks of late stochastic effects such as leukemia. This ... Full text Open Access Cite

Trade-offs between cancer and other diseases: do they exist and influence longevity?

Journal Article Rejuvenation research · August 2010 Relationships between aging, disease risks, and longevity are not yet well understood. For example, joint increases in cancer risk and total survival observed in many human populations and some experimental aging studies may be linked to a trade-off betwee ... Full text Open Access Cite

Leukocyte telomere length is associated with disability in older u.s. Population.

Journal Article Journal of the American Geriatrics Society · July 2010 ObjectivesTo determine whether mean leukocyte telomere length (LTL) serves as a biomarker of disability assessed according to activities of daily living (ADLs) and what factors may modify this relationship.DesignRetrospective cross-sectio ... Full text Open Access Cite

Exceptional survivors have lower age trajectories of blood glucose: lessons from longitudinal data.

Journal Article Biogerontology · June 2010 Exceptional survival results from complicated interplay between genetic and environmental factors. The effects of these factors on survival are mediated by the biological and physiological variables, which affect mortality risk. In this paper, we evaluated ... Full text Cite

Early hematopoiesis inhibition under chronic radiation exposure in humans.

Journal Article Radiation and environmental biophysics · May 2010 The major goal of this study was to identify and quantitatively describe the association between the characteristics of chronic (low-dose rate) exposure to (low LET) ionizing radiation and cellularity of peripheral blood cell lines. About 3,200 hemograms ( ... Full text Open Access Cite

Beta2-adrenergic receptor gene polymorphisms as systemic determinants of healthy aging in an evolutionary context.

Journal Article Mechanisms of ageing and development · May 2010 The Gln(27)Glu polymorphism but not the Arg(16)Gly polymorphism of the beta2-adrenergic receptor (ADRB2) gene appears to be associated with a broad range of aging-associated phenotypes, including cancers at different sites, myocardial infarction (MI), inte ... Full text Open Access Cite

"Predicting" parental longevity from offspring endophenotypes: data from the Long Life Family Study (LLFS).

Journal Article Mechanisms of ageing and development · March 2010 While there is evidence that longevity runs in families, the study of long-lived families is complicated by the fact that longevity-related information is available only for the oldest old, many of whom may be deceased and unavailable for testing, and info ... Full text Cite

Trends in survival and recovery from stroke: evidence from the National Long-Term Care Survey/Medicare data.

Journal Article Stroke · March 2010 Background and purposeImprovements in recovery rates may contribute to an increase in healthy life expectancy. It is unclear, however, whether such changes take place because health researchers traditionally deal with changes in incidence and surv ... Full text Cite

Polymorphisms in the ACE and ADRB2 genes and risks of aging-associated phenotypes: the case of myocardial infarction.

Journal Article Rejuvenation research · February 2010 Multiple functions of the beta2-adrenergic receptor (ADRB2) and angiotensin-converting enzyme (ACE) genes warrant studies of their associations with aging-related phenotypes. We focus on multimarker analyses and analyses of the effects of compound genotype ... Full text Open Access Cite

Dynamic determinants of longevity and exceptional health.

Journal Article Curr Gerontol Geriatr Res · 2010 It is well known from epidemiology that values of indices describing physiological state in a given age may influence human morbidity and mortality risks. Studies of connection between aging and life span suggest a possibility that dynamic properties of ag ... Full text Link to item Cite

A new approach to individual prognostication of cancer development under conditions of chronic radiation exposure

Journal Article International Journal of Low Radiation · January 1, 2010 This paper describes a new approach to modelling carcinogenesis, including that induced by ionising radiation. The specific feature of the developed approach is that the model, still adhering to the mutational theory of carcinogenesis, includes parameters ... Full text Cite

A bivariate survival model with compound Poisson frailty.

Journal Article Statistics in medicine · January 2010 A correlated frailty model is suggested for analysis of bivariate time-to-event data. The model is an extension of the correlated power variance function (PVF) frailty model (correlated three-parameter frailty model) (J. Epidemiol. Biostat. 1999; 4:53-60). ... Full text Cite

Date of eclosion modulates longevity: insights across dietary-restriction gradients and female reproduction in the mexfly Anastrepha ludens.

Journal Article Experimental gerontology · November 2009 We use unique experimental data on daily reproduction and survival of individual fruit flies from eight cohorts eclosed at different dates in 2004 and 2005 who were treated with varying proportions of sugar and yeast and subject to different caloric restri ... Full text Cite

Hormesis against aging and diseases: using properties of biological adaptation for health and survival improvement.

Journal Article Dose-response : a publication of International Hormesis Society · October 2009 The idea of using hormesis for postponing aging and improving human health has been recently discussed in scientific literature. This paper shows that redundancy in renewal capacity, some portion of which become activated and manifested in hormesis effects ... Full text Cite

DYNAMIC DETERMINANTS OF EXCEPTIONAL HEALTH AND LONGEVITY

Journal Article GERONTOLOGIST · October 1, 2009 Link to item Cite

Multiple mild heat-shocks decrease the Gompertz component of mortality in Caenorhabditis elegans.

Journal Article Experimental gerontology · September 2009 Exposure to mild heat-stress (heat-shock) can significantly increase the life expectancy of the nematode Caenorhabditis elegans. A single heat-shock early in life extends longevity by 20% or more and affects life-long mortality by decreasing initial mortal ... Full text Cite

Maintaining physiological state for exceptional survival: What is the normal level of blood glucose and does it change with age?

Journal Article Mechanisms of ageing and development · September 2009 The levels of blood glucose (BG) in humans tend to increase with age deviating from the norm specified for the young adults. Such elevation is often considered as a factor contributing to an increase in risks of disease and death. The proper use of interve ... Full text Cite

Genetic model for longitudinal studies of aging, health, and longevity and its potential application to incomplete data.

Journal Article Journal of theoretical biology · May 2009 Many longitudinal studies of aging collect genetic information only for a sub-sample of participants of the study. These data also do not include recent findings, new ideas and methodological concepts developed by distinct groups of researchers. The formal ... Full text Cite

Studying health histories of cancer: a new model connecting cancer incidence and survival.

Journal Article Mathematical biosciences · April 2009 The results of recent experimental and epidemiological studies provide evidence on the connection between carcinogenesis, cancer progression, and aging. Existing models, however, are traditionally focused only on one of these aspects of health deterioratio ... Full text Cite

Leukocyte telomere dynamics and human hematopoietic stem cell kinetics during somatic growth.

Journal Article Experimental hematology · April 2009 ObjectiveA central question in stem cell research is knowing the frequency of human hematopoietic stem cells (HSC) replication in vivo.Materials and methodsWe have constructed a model that characterizes HSC kinetics and the relative sizes ... Full text Cite

Mathematical modeling of immunosenescence: Scenarios, processes and limitations

Chapter · January 1, 2009 Mathematical modeling of immunosenescence is the new area of research emerging at the interface of the immunology, gerontology, and mathematics. In this paper we outline basic variables important for modeling aging immunity. We discuss the role of evolutio ... Full text Cite

Linear latent structure analysis and modelling of multiple categorical variables

Journal Article Computational and Mathematical Methods in Medicine · January 1, 2009 Linear latent structure analysis is a new approach for investigation of population heterogeneity using high-dimensional categorical data. In this approach, the population is represented by a distribution of latent vectors, which play the role of heterogene ... Full text Cite

Health-related phenotypes and longevity in danish twins.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · January 2009 Aging studies can be facilitated by refocusing from longevity phenotypes to their proxies (intermediate phenotypes). Robust selection of the intermediate phenotypes requires data on such phenotypes and life span measured in the same individuals, which is n ... Full text Cite

Trade-off between cancer and aging: what role do other diseases play? Evidence from experimental and human population studies.

Journal Article Mechanisms of ageing and development · January 2009 The potential gain in life expectancy which could result from the complete elimination of mortality from cancer in the U.S. would not exceed 3 years if one were to consider cancer independently of other causes of death. In this paper, we review evidence of ... Full text Cite

Sex-specific health deterioration and mortality: the morbidity-mortality paradox over age and time.

Journal Article Experimental gerontology · December 2008 The traditional sex morbidity-mortality paradox that females have worse health but better survival than males is based on studies of major health traits. We applied a cumulative deficits approach to study this paradox, selecting 34 minor health deficits co ... Full text Cite

Circulatory diseases and aging

Journal Article · December 1, 2008 Age patterns of incidence rates of major circulatory diseases (CDs), their time trends, risk factors, and other characteristics capable of contributing to the debates on the role of aging in the deterioration of human health are investigated using standard ... Full text Cite

Cumulative deficits and physiological indices as predictors of mortality and long life.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · October 2008 We evaluated the predictive potential for long-term (24-year) survival and longevity (85+ years) of an index of cumulative deficits (DI) and six physiological indices (pulse pressure, diastolic blood pressure, pulse rate, serum cholesterol, blood glucose, ... Full text Cite

Changes in health status among participants of the Framingham Heart Study from the 1960s to the 1990s: application of an index of cumulative deficits.

Journal Article Annals of epidemiology · September 2008 PurposeHealth of the general population is improving along a number of major health dimensions. Using a cumulative deficits approach, we investigated whether such improvements were evident at the level of minor health traits.MethodsWe sel ... Full text Cite

The U-shaped response of initial mortality in Caenorhabditis elegans to mild heat shock: does it explain recent trends in human mortality?

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · July 2008 U-shaped dose-response relationships (hormesis) have been documented in numerous biological, toxicological, and pharmacological investigations. For example, in response to a mild 35 degrees C heat shock, the longevity of Caenorhabditis elegans exhibits an ... Full text Cite

Cumulative deficits better characterize susceptibility to death in elderly people than phenotypic frailty: lessons from the Cardiovascular Health Study.

Journal Article Journal of the American Geriatrics Society · May 2008 ObjectivesTo compare how well frailty measures based on a phenotypic frailty approach proposed in the Cardiovascular Health Study (CHS) and a cumulative deficits approach predict mortality.DesignCohort study.SettingThe main cohor ... Full text Cite

Association between APOE epsilon 2/epsilon 3/epsilon 4 polymorphism and disability severity in a national long-term care survey sample.

Journal Article Age and ageing · May 2008 Backgroundearly studies reported controversial findings on association of apolipoprotein E (APOE) polymorphism with disability.Objectiveto analyse sex-specific associations of APOE genotypes with impairments in (instrumental) activities o ... Full text Cite

What age trajectories of cumulative deficits and medical costs tell us about individual aging and mortality risk: Findings from the NLTCS-Medicare data.

Journal Article Mechanisms of ageing and development · April 2008 An important feature of aging-related deterioration in human health is the decline in organisms' resistance to stresses, which contributes to an increase in morbidity and mortality risks. In human longitudinal studies of aging, such a decline is not measur ... Full text Cite

Health-protective and adverse effects of the apolipoprotein E epsilon2 allele in older men.

Journal Article J Am Geriatr Soc · March 2008 OBJECTIVES: To reexamine a health-protective role of the common apolipoprotein E (APOE) polymorphism focusing on connections between the APOE epsilon2-containing genotypes and impairments in instrumental activities of daily living (IADLs) in older (> or = ... Full text Link to item Cite

An inverse association between self-reported arthritis and mortality in the elderly: findings from the national long-term care survey.

Journal Article Rejuvenation research · February 2008 Major musculoskeletal conditions including arthritis represent an increasing burden on individuals and societies. We analyzed the association between self-reported arthritis and mortality in the U.S. elderly disabled and non-disabled individuals using uniq ... Full text Cite

Model of hidden heterogeneity in longitudinal data.

Journal Article Theoretical population biology · February 2008 Variables measured in longitudinal studies of aging and longevity do not exhaust the list of all factors affecting health and mortality transitions. Unobserved factors generate hidden variability in susceptibility to diseases and death in populations and i ... Full text Cite

Body mass index and nine-year mortality in disabled and nondisabled older U.S. individuals.

Journal Article Journal of the American Geriatrics Society · January 2008 ObjectivesTo investigate the relationship between body mass index (BMI) and 9-year mortality in older (> or = 65) Americans with and without disability.DesignCohort study.SettingThe unique disability-focused National Long Term Ca ... Full text Cite

Epidemiology of hormone-associated cancers as a reflection of age.

Journal Article Advances in experimental medicine and biology · January 2008 In this chapter we review the epidemiology of hormone-associated cancers (prostate, breast, endometrial, ovarian, pancreatic and thyroid) paying special attention to the variability in the age patterns of cancer incidence rate over populations and time per ... Full text Cite

Nonpathological senescence arises from unsuitable external influences.

Journal Article Annals of the New York Academy of Sciences · November 2007 One of the most exciting events in current biogerontology is the elucidation of environmental control over the rate of aging. Many observations suggest that appropriate external stimuli can ameliorate the state of various biological entities and even rejuv ... Full text Cite

Accelerated accumulation of health deficits as a characteristic of aging.

Journal Article Experimental gerontology · October 2007 Cross-sectional analyses show that an index of aging-associated health/well-being deficits, called the "frailty index", can characterize the aging process in humans. This study provides support for such characterization from a longitudinal analysis of the ... Full text Cite

A correlated frailty model with long-term survivors for estimating the heritability of breast cancer.

Journal Article Statistics in medicine · September 2007 The aim of this study is to investigate the role of genetics and environment in susceptibility to breast cancer (frailty). An interdisciplinary approach was adopted, combining a correlated frailty-mixture model with genetic equations, allowing for decompos ... Full text Cite

The apolipoprotein E epsilon2 allele and aging-associated health deterioration in older males.

Journal Article Journal of the American Geriatrics Society · September 2007 Full text Cite

Stochastic model for analysis of longitudinal data on aging and mortality.

Journal Article Mathematical biosciences · August 2007 Aging-related changes in a human organism follow dynamic regularities, which contribute to the observed age patterns of incidence and mortality curves. An organism's 'optimal' (normal) physiological state changes with age, affecting the values of risks of ... Full text Cite

Cumulative index of health deficiencies as a characteristic of long life.

Journal Article Journal of the American Geriatrics Society · June 2007 ObjectivesTo describe the accumulation of aging-associated health disorders using a cumulative measure known as a frailty index (FI) and to evaluate its ability to differentiate long- and short-life phenotypes as well as the FI's connection to agi ... Full text Cite

The accuracy of statistical estimates in genetic studies of aging can be significantly improved.

Journal Article Biogerontology · June 2007 The sample size of the data used in genetic studies is often a factor limiting the accuracy of statistical estimates. In this paper we suggest a new approach to evaluation of genetic influence on risk of development of aging-related health disorders. The a ... Full text Cite

Health decline, aging and mortality: how are they related?

Journal Article Biogerontology · June 2007 The deterioration of human health with age is manifested in changes of thousands of physiological and biological variables. The contribution of some of such changes to the mortality risk may be small and cannot be reliably detected by existing statistical ... Full text Cite

Cumulative index of health disorders as an indicator of aging-associated processes in the elderly: results from analyses of the National Long Term Care Survey.

Journal Article Mechanisms of ageing and development · March 2007 BackgroundWe employ an approach based on the elaborated frailty index (FI), which is capable of taking into account variables with mild effect on the aging, health and survival outcomes, and investigate the connections between the FI, chronologica ... Full text Cite

Cumulative index of elderly disorders and its dynamic contribution to mortality and longevity.

Journal Article Rejuvenation research · March 2007 The composite index constructed from longitudinal survey data as the level of deficits accumulated by an individual (frailty index) captures important systemic aspects of deterioration in a human organism, and is an attractive candidate for studying determ ... Full text Cite

Insights on aging and exceptional longevity from longitudinal data: novel findings from the Framingham Heart Study.

Journal Article Age (Dordrecht, Netherlands) · December 2006 Age trajectories of physiological indices contain important information about aging-related changes in the human organism and therefore may help us understand human longevity. The goal of this study is to investigate whether shapes of such trajectories ear ... Full text Cite

Accumulation of health disorders as a systemic measure of aging: Findings from the NLTCS data.

Journal Article Mechanisms of ageing and development · November 2006 BackgroundAn index of age-associated health/well-being disorders (deficits), called the "frailty index" (FI), appears to be a promising characteristic to capture dynamic variability in aging manifestations among age-peers. In this study we provide ... Full text Cite

Decrease in the lgl tumor suppressor dose in Drosophila increases survival and longevity in stress conditions.

Journal Article Experimental gerontology · September 2006 Recent studies suggest that downregulation of tumor suppressor genes might not only favor cancer development but also postpone organisms' aging and increase longevity. However, there is lack of population-based studies directly supporting this idea. We stu ... Full text Cite

Increasing rates of dementia at time of declining mortality from stroke.

Journal Article Stroke · May 2006 Background and purposeStroke is associated with increased risk of dementia. There has been a decline in mortality from stroke among persons 65 and over in recent decades in the US. It is not clear, however, how this process has affected incidence ... Full text Cite

Inadequate intensity of various components of total environmental signals can lead to natural aging.

Journal Article Annals of the New York Academy of Sciences · May 2006 We suppose that natural aging derives from an inevitable shift in certain parameters of physiological control systems under the influence of inadequate environmental conditions, which are not able to fully induce an organism's "optimal" existence in the se ... Full text Cite

Visualizing hidden heterogeneity in isogenic populations of C. elegans.

Journal Article Experimental gerontology · March 2006 Age-specific mortality levels off at advanced ages in many species; one explanation for this phenomenon is provided by the population heterogeneity theory. Although mortality at advanced ages can be well fit by heterogeneity models, population heterogeneit ... Full text Cite

Two proofs of a recent formula by Griffith Feeney

Journal Article Demographic Research · January 26, 2006 This reflexion provides two mathematical proofs for Equation (1) in Feeney (2006), published in this journal as 14-2. © 2006 Max-Planck-Gesellschaft. ... Full text Cite

Population models for the health effects of ionizing radiation.

Journal Article Radiats Biol Radioecol · 2006 In this paper we review recently-developed extension frailty, quadratic hazard, stochastic process, microsimulation, and linear latent structure models, which have the potential to describe the health effects of human populations exposed to ionizing radiat ... Link to item Cite

Central and peripheral effects of insulin/IGF-1 signaling in aging and cancer: antidiabetic drugs as geroprotectors and anticarcinogens.

Journal Article Annals of the New York Academy of Sciences · December 2005 Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors both in aging and in the development of cancer. Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules linked to longevity include DAF-2 a ... Full text Cite

A comparison of different bivariate correlated frailty models and estimation strategies.

Journal Article Mathematical biosciences · November 2005 Frailty models are becoming increasingly popular in multivariate survival analysis. Shared frailty models in particular are often used despite their limitations. To overcome their disadvantages numerous correlated frailty models were established during the ... Full text Cite

Cancer in rodents: does it tell us about cancer in humans?

Journal Article Nature reviews. Cancer · October 2005 Information obtained from animal models (mostly mice and rats) has contributed substantially to the development of treatments for human cancers. However, important interspecies differences have to be taken into account when considering the mechanisms of ca ... Full text Cite

Individual fecundity and senescence in Drosophila and medfly.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · August 2005 Evolutionary theory postulates that there should be a robust relationship between fecundity and longevity. Prior work has generally supported this concept, but has not shed much light on the mechanisms at play. In preceding work, we have developed and veri ... Full text Cite

Decline in human cancer incidence rates at old ages: Age-period-cohort considerations

Journal Article Demographic Research · May 13, 2005 Analysis of age-specific trajectories of cancer incidence rates for all sites combined (data source: International Agency for Research on Cancer) reveals a leveling-off and decline of the rates at old ages in different countries and time periods. We apply ... Full text Cite

Mathematical models for human cancer incidence rates

Journal Article Demographic Research · May 7, 2005 The overall cancer incidence rate declines at old ages. Possible causes of this decline include the effects of cross-sectional data that transform cohort dynamics into age patterns, population heterogeneity that selects individuals susceptible to cancer, a ... Full text Cite

Insulin in aging and cancer: antidiabetic drug Diabenol as geroprotector and anticarcinogen.

Journal Article The international journal of biochemistry & cell biology · May 2005 The effects of new antidiabetic drug Diabenol (9-beta-diethylaminoethyl-2,3-dihydroimidazo-(1,2-alpha)benzimidazol dihydrochloride) on life span and spontaneous tumor incidence in NMRI and transgenic HER-2/neu mice as well as on colon carcinogenesis induce ... Full text Cite

What evidence is there for the existence of individual genes with antagonistic pleiotropic effects?

Journal Article Mechanisms of ageing and development · March 2005 Classical evolutionary theory predicts the existence of genes with antagonistic effects on longevity and various components of early-life fitness. Quantitative genetic studies have provided convincing evidence that such genes exist. However, antagonistic p ... Full text Cite

The heritability of CHD mortality in danish twins after controlling for smoking and BMI.

Journal Article Twin research and human genetics : the official journal of the International Society for Twin Studies · February 2005 Cause-specific mortality data on Danish monozygotic and dizygotic twins are used to analyze heritability estimates of susceptibility to coronary heart disease (CHD) after controlling for smoking and Body Mass Index (BMI). The sample includes 1209 like-sexe ... Full text Cite

Genetic markers data in survival studies of twins: the results of a simulation study.

Journal Article Twin research and human genetics : the official journal of the International Society for Twin Studies · February 2005 Previous longevity studies of related individuals such as twins or siblings based on the major gene model have shown that the frequency and the relative risk of mortality of a beneficial allele in the population could be estimated. If, in addition to survi ... Full text Cite

Estimating haplotype relative risks on human survival in population-based association studies.

Journal Article Human heredity · January 2005 Association-based linkage disequilibrium (LD) mapping is an increasingly important tool for localizing genes that show potential influence on human aging and longevity. As haplotypes contain more LD information than single markers, a haplotype-based LD app ... Full text Cite

[Effect of epitalon and melatonin on life span and spontaneous carcinogenesis in senescence accelerated mice (SAM)].

Journal Article Voprosy onkologii · January 2005 Female senescence accelerated mice SAMP-1. (prone) and SAMR-1 (resistant) were exposed 5 times a week monthly to melatonin (with drinking water 20mg/ml during the night hours) or to s.c. injections of epitalon (Ala-Glu-Asp-Gly) at a single dose 1mkg/mouse. ... Cite

Treating cancer with embryonic stem cells: rationale comes from aging studies.

Journal Article Frontiers in bioscience : a journal and virtual library · January 2005 In an earlier poster paper (1) we proposed that cancer can be viewed not only as a fatal disease but also as a local aberrant, rejuvenation, in an organism, and this fact can be useful for developing new anti-aging and anti-cancer treatments. In this paper ... Full text Cite

The effect of the organisms' body size and energy reserves in models for population dynamics

Journal Article Journal of Biological Systems · December 1, 2004 We present two models suitable for describing dynamics of a population of unicellular organisms residing in chemostat. These models are based on biologically motivated Dynamic Energy Budget (DEB) theory and take into account the dynamics of mean energy res ... Full text Cite

Model of resource reallocation during physiological adaptation of females of the Mediterranean fruit fly Ceratitis capitata

Journal Article Biophysics · December 1, 2004 The results of studying the life span and fertility of females of the Mediterranean fruit fly Ceratitis capitata suggest that an increase in the mean life span is accompanied by a proportional decrease in the mean number of eggs laid. At the same time, the ... Cite

Genetic influences on CHD-death and the impact of known risk factors: comparison of two frailty models.

Journal Article Behavior genetics · November 2004 The importance of some recognized risk factors on genetic influences for coronary heart disease (CHD) needs further clarification. The aim of the present study was therefore to study the impact of known risk factors on genetic influences for CHD-death. Bot ... Full text Cite

Stressors and antistressors: how do they influence life span in HER-2/neu transgenic mice?

Journal Article Experimental gerontology · October 2004 The purpose of this study is to investigate possible influences of different stressors (saline injections, light deprivation and constant light regimen) and geroprotectors (Epitalon and melatonin) on survivals of female HER-2/neu transgenic mice. We propos ... Full text Cite

Effect of exposure to light-at-night on life span and spontaneous carcinogenesis in female CBA mice.

Journal Article International journal of cancer · September 2004 The effect of constant illumination on the development of spontaneous tumors in female CBA mice was investigated. Fifty female CBA mice starting from the age of 2 months were kept under standard light/dark regimen (12 hr light:12 hr dark; LD) and 50 CBA mi ... Full text Cite

[A model of resource reallocation during physiological adaptation in Mediterranean fruit fly females].

Journal Article Biofizika · September 2004 Analysis of experimental data on longevity and fertility of females of Mediterranean fruit fly Ceratitis capitata demonstrates that flies lay fewer eggs on the average as the average life-span increases. At the same time, the values of individual life-span ... Cite

Immune system aging may be affected by HIV infection: The mathematical model of immunosenescence

Journal Article Russian Journal of Numerical Analysis and Mathematical Modelling · August 23, 2004 In this paper, we analyse the structure of equations in the earlier proposed mathematical model of the dynamics of age-related changes in population of peripheral T lymphocytes. To investigate behaviour of the model solutions in a wide range of values of v ... Full text Cite

Multidisciplinary approaches in genetic studies of human aging and longevity

Journal Article Current Genomics · July 1, 2004 The amount of research on human aging and longevity has been growing rapidly in recent years. Multidisciplinary approaches, which integrate classic population genetics methods with the principles of epidemiological and demographic investigation, are emergi ... Full text Cite

How an individual fecundity pattern looks in Drosophila and medflies.

Journal Article Annals of the New York Academy of Sciences · June 2004 Reproduction usually is characterized by a mean-population fecundity pattern. Such a pattern has a maximum at earlier ages and a subsequent gradual decline in egg production. It is shown that individual fecundity trajectories do not follow such a pattern. ... Full text Cite

Antiaging treatments have been legally prescribed for approximately thirty years.

Journal Article Annals of the New York Academy of Sciences · June 2004 There is an interesting divergence between the achievements of geriatrics and gerontology. On the one hand, during the last 30 years physicians in many developed countries have successfully prescribed several medicines to cure various symptoms of senescenc ... Full text Cite

Cancer as "rejuvenescence".

Journal Article Annals of the New York Academy of Sciences · June 2004 Comparative analysis of malignant and senescent cells shows that their phenotypic features are in many instances contrary. Cancer cells do not "age"; their metabolic and growth characteristics are opposite to those observed with cellular aging (both replic ... Full text Cite

The impact of diet switching on resource allocation to reproduction and longevity in Mediterranean fruitflies.

Journal Article Proceedings. Biological sciences · June 2004 Understanding the factors that determine the allocation and utilization of organism resources may provide an insight into the mechanisms of adaptation, ageing and reproduction. Resource allocation, which is regarded as a method of adaptation, increases fit ... Full text Cite

Is early life body weight a predictor of longevity and tumor risk in rats?

Journal Article Experimental gerontology · May 2004 Heavy body weight (BW) is thought to be associated with reduced longevity and age-associated diseases, including cancer, both in laboratory rodents and humans. To further investigate the interactions between BW, longevity and spontaneous tumor development, ... Full text Cite

The heritability of breast cancer: a Bayesian correlated frailty model applied to Swedish twins data.

Journal Article Twin research : the official journal of the International Society for Twin Studies · April 2004 The aim of this study was to investigate the role of genes and environment in susceptibility to breast cancer and to give an estimate of heritability in the propensity to develop the disease. To do this we applied an interdisciplinary approach, merging mod ... Full text Cite

Body weight is not always a good predictor of longevity in mice.

Journal Article Experimental gerontology · March 2004 There have been some observations that low body weight and a low level of some hormones (e.g. IGF-1) during the first half of life are predictors of longer life in mice. However, contradictions in the available data on the biomarkers of aging and predictor ... Full text Cite

Assessing genetic association with human survival at multi-allelic loci.

Journal Article Biogerontology · January 2004 Genetic variation plays an important role in natural selection and population evolution. However, it also presents geneticists interested in aging research with problems in data analysis because of the large number of alleles and their various modes of act ... Full text Cite

[Effect of light deprivation on homeostasis, life span and development of spontaneous tumors in HER-2/neu transgenic mice].

Journal Article Voprosy onkologii · January 2004 Twenty five female HER-2/neu transgenic mice (FVB/N), aged 2 months, were surgically deprived of lighting; 30 intact transgenic mice, kept under standard conditions, were in control. Light deprivation was followed by inhibited intake of feed, decreased bod ... Cite

[Serotonin transporter gene polymorphism and factors influencing mental and physical health in aging].

Journal Article Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · January 2004 Genetic predisposition is thought to exert a certain influence on the indices related to longevity and quality of life. Many of the indices, namely cognitive functioning, stress resistance, metabolism control, may be related to serotonin activity. To study ... Cite

Disability trends in gender and race groups of early retirement ages in the USA.

Journal Article Sozial- und Praventivmedizin · January 2004 ObjectivesTo analyse disability trends over the 1980s-1990s in gender and race groups of early retirement ages in USA.MethodsDisability trends for white and black males and females aged 65-69 and 70+ are analysed using the 1982-1999 NLTCS ... Full text Cite

Stress resistance declines with age: analysis of data from a survival experiment with Drosophila melanogaster.

Journal Article Biogerontology · January 2004 An approach towards analyzing survivorship data is proposed for the study of changes in stress resistance with age in the population of Drosophila melanogaster. This is based on the model of heterogeneous mortality (frailty model). Results of the data anal ... Full text Cite

Systemic mechanisms of individual reproductive life history in female Medflies.

Journal Article Mechanisms of ageing and development · January 2004 This paper is the second one in a series of two papers hypothesizing and testing systemic grounds of reproductive life history in the female fruit fly. In the first paper, we analyzed mechanisms of individual fecundity scheduling and have drawn the followi ... Full text Cite

The heritability of cause-specific mortality: a correlated gamma-frailty model applied to mortality due to respiratory diseases in Danish twins born 1870-1930.

Journal Article Statistics in medicine · December 2003 The genetic influence on susceptibility to diseases of the respiratory system and all-cause mortality was studied using data for identical (MZ) and fraternal (DZ) twins. Data from the Danish Twin Register include 1344 MZ and 2411 DZ male twin pairs and 147 ... Full text Cite

A bivariate frailty model with a cure fraction for modeling familial correlations in diseases.

Journal Article Biometrics · December 2003 We suggest a cure-mixture model to analyze bivariate time-to-event data, as motivated by the article of Chatterjee and Shih (2001, Biometrics 57, 779-786), but with a simpler estimation procedure and the correlated gamma-frailty model instead of the shared ... Full text Cite

Effect of neuronol on lifespan and development of spontaneous tumors in SAMP-1 mice with genetically accelerated aging.

Journal Article Bulletin of experimental biology and medicine · December 2003 Treatment of female SAMP-1 mice with Neuronol (drug containing succinic acid) given with drinking water starting from the age of 2 months during the whole life prolonged the lifespan and markedly reduced mortality of animals aged 1.5-2 years. Neuronol inhi ... Full text Cite

Opposite phenotypes of cancer and aging arise from alternative regulation of common signaling pathways.

Journal Article Annals of the New York Academy of Sciences · December 2003 Phenotypic features of malignant and senescent cells are in many instances opposite. Cancer cells do not "age"; their metabolic, proliferative, and growth characteristics are opposite to those observed with cellular aging (both replicative and functional). ... Full text Cite

Logistic regression models for polymorphic and antagonistic pleiotropic gene action on human aging and longevity.

Journal Article Annals of human genetics · November 2003 In this paper, we apply logistic regression models to measure genetic association with human survival for highly polymorphic and pleiotropic genes. By modelling genotype frequency as a function of age, we introduce a logistic regression model with polytomo ... Full text Cite

Individual aging and cancer risk: How are they related?

Journal Article Demographic Research · October 30, 2003 When individuals get older, the risk of many chronic diseases increases. This increase is in agreement with common theories of aging, such as mutation accumulation, wear and tear, antagonistic pleiotropy, etc. Surprisingly, however, the risk of some chroni ... Full text Cite

Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly.

Journal Article Experimental gerontology · October 2003 The human sirtuin 3 (SIRT3) gene encodes a putative mitochondrial NAD-dependent deacetylase (SIRT3) which belongs to the evolutionary conserved family of sirtuin 2 proteins. Studies in model organisms have demonstrated that SIR2 genes control lifespan, whi ... Full text Cite

Effect of delta-sleep inducing peptide-containing preparation Deltaran on biomarkers of aging, life span and spontaneous tumor incidence in female SHR mice.

Journal Article Mechanisms of ageing and development · June 2003 From the age of 3 months until their natural deaths, female Swiss-derived SHR mice were subcutaneously injected 5 consecutive days every month with 0.1 ml of normal saline (control) or with 2.5 microg/mouse (approximately 100 microg/kg) of delta-sleep indu ... Full text Cite

What fecundity patterns indicate about aging and longevity: insights from Drosophila studies.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · June 2003 The age pattern of fecundity is represented as a result of a superposition of two processes: the genetic fecundity program encoded in the organism's reproductive machinery and senescence of the reproductive system. Accumulation of oxidative damage produces ... Full text Cite

What does a fly's individual fecundity pattern look like? The dynamics of resource allocation in reproduction and ageing.

Journal Article Mechanisms of ageing and development · May 2003 Reproduction is usually characterised by an average fecundity pattern having a maximum at earlier ages and a subsequent gradual decline later on. An individual fecundity trajectory does not follow such a pattern and has no maximum. A three-stage pattern, w ... Full text Cite

Age related changes in population of peripheral T cells: towards a model of immunosenescence.

Journal Article Mechanisms of ageing and development · April 2003 In this paper, we presented the results of analysis of experimental evidence for the decline of the human immune system functioning with age using mathematical model of immunosenescence. The most prominent changes in this system are related to the decline ... Full text Cite

Number of pregnancies and ovariectomy modify mammary carcinoma development in transgenic HER-2/neu female mice.

Journal Article Cancer letters · April 2003 We studied effect of pregnancy and ovariectomy on the development of mammary tumors in homozygous female HER-2/neutransgenic mice. The mean life span of uniparous mice was decreased by 16% in comparison to the control (P<0.05) and of mice which have two pr ... Full text Cite

Dose-dependent effect of melatonin on life span and spontaneous tumor incidence in female SHR mice.

Journal Article Experimental gerontology · April 2003 From the age of 3 months until their natural death, female Swiss-derived SHR mice were given melatonin with their drinking water (2 or 20mg/l) for 5 consecutive days every month. Intact mice served as controls. There were 54 mice in each group. The results ... Full text Cite

The effect of melatonin treatment regimen on mammary adenocarcinoma development in HER-2/neu transgenic mice.

Journal Article International journal of cancer · January 2003 The effect of various regimens of treatment with melatonin on the development of mammary tumors in HER2/neu transgenic mice was investigated. Female HER-2/neu mice starting from the age of 2 months were kept under standard light/dark regimen and as given m ... Full text Cite

How the analysis of genetic mutations can help us to solve basic problems in gerontology? I. Life extending genetic modifications in round worm C. elegans.

Journal Article Advances in gerontology = Uspekhi gerontologii · January 2003 The results of recent molecular biological studies of aging and longevity confirmed substantial genetic contribution to the life span. The analysis of these findings showed substantial role of specific mutations in genes involved in regulatory processes on ... Cite

Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice.

Journal Article Biogerontology · January 2003 From the age of 3 months until their natural deaths, female outbred Swiss-derived SHR mice were subcutaneously injected on 5 consecutive days every month with 0.1 ml of normal saline (control) or with 1.0 microg/mouse (approximately 30-40 microg/kg) of tet ... Full text Cite

How the analysis of genetic mutations can help us to solve basic problems in gerontology? II. Life extending genetic modifications in budding yeast S. cereviseae, fruit fly D. melanogaster and laboratory mice M. musculus.

Journal Article Advances in gerontology = Uspekhi gerontologii · January 2003 Most studies of aging are conducted in humans and domestic or laboratory animals, i.e. in conditions where artificial environment protection is applied, This yields changes in physiology and behavior, which set up organism's state unobserved in wild life. ... Cite

Reproduction and survival in Mediterranean fruit flies: a "protein and energy" free radical model of aging.

Journal Article Biogerontology · January 2003 We propose a "protein and energy" free radical model of aging that predicts patterns of survival and fertility curves for Mediterranean fruit flies. Mathematical and simulation models of individual physiological processes were constructed in terms of stoch ... Full text Cite

Insulin and longevity: antidiabetic biguanides as geroprotectors.

Journal Article Biogerontology · January 2003 The results of previous experimental studies of effects of antidiabetic biguanides (phenformin and buformin) on life span and spontaneous tumor incidence in mice and rats were recalculated and reanalyzed using standard demographic models of mortality. The ... Full text Cite

Male/female ratio in centenarians: a possible role played by population genetic structure.

Journal Article Experimental gerontology · October 2002 All the demographic surveys on the centenarians have highlighted that females outnumber males. The centenarians' male/female (M/F) ratio reported by most studies ranges between 1:4 and 1:7. A puzzling 1:2 ratio was observed in Calabria, a Southern Italian ... Full text Cite

A multistate model for the genetic analysis of the ageing process.

Journal Article Statistics in medicine · September 2002 In this paper a multivariate frailty model is suggested that can be used in the genetic analysis of the ageing process as a whole, simplified to consisting of the states 'healthy', 'disabled' and 'deceased'. The model allows us to evaluate simultaneously t ... Full text Cite

Individual aging and mortality rate: how are they related?

Journal Article Social biology · September 2002 Many researchers working in the area of aging and longevity base their conclusions on the behavior of empirical age trajectories of mortality rates. In such analyses, changes in the slope of the logarithm of the mortality curve are often associated with ch ... Full text Cite

Heritability of death from coronary heart disease: a 36-year follow-up of 20 966 Swedish twins.

Journal Article Journal of internal medicine · September 2002 ObjectiveThe aim of the present study was to evaluate and distinguish between environmental and genetic effects for death from coronary heart disease (CHD) as well as to determine whether the importance of genetic influences is changing with age.< ... Full text Cite

Epithalon decelerates aging and suppresses development of breast adenocarcinomas in transgenic her-2/neu mice.

Journal Article Bulletin of experimental biology and medicine · August 2002 Female transgenic FVB/N mice carrying the breast cancer gene HER-2/neu received epithalon (Ala-Glu-Asp-Gly) in a dose of 1 mg subcutaneously 5 times a week to from the 2nd month of life to death. Epithalon prolonged the average and maximum lifetimes of mic ... Full text Cite

The influences on human longevity by HUMTHO1.STR polymorphism (Tyrosine Hydroxylase gene). A relative risk approach.

Journal Article Mechanisms of ageing and development · July 2002 A new method based on the recently developed relative risk approach is introduced, and applied to data from Italian centenarian study (965 subjects aged from 13 to 109 years old) for investigating influences on longevity by Tyrosine Hydroxylase (TH) gene v ... Full text Cite

Evolutionary optimality applied to Drosophila experiments: hypothesis of constrained reproductive efficiency.

Journal Article Evolution; international journal of organic evolution · June 2002 The general purpose of the paper is to test evolutionary optimality theories with experimental data on reproduction, energy consumption, and longevity in a particular Drosophila genotype. We describe the resource allocation in Drosophila females in terms o ... Full text Cite

A case-only approach for assessing gene by sex interaction in human longevity.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · April 2002 As one aspect of the complex feature of longevity, gene by sex interaction plays an important role in influencing human life span. With advances in molecular genetics, more studies aimed at assessing gene by sex interaction are expected. New and valid stat ... Full text Cite

An allele of HRAS1 3'variable number of tandem repeats is a frailty allele: implication for an evolutionarily-conserved pathway involved in longevity.

Journal Article Gene · March 2002 The human HRAS1 belongs to an evolutionarily-conserved family of genes which enrolls among its members the yeast RAS2, a gene which regulates stress response and longevity in the Saccharomyces cerevisiae. In this paper we report that the frequency of the a ... Full text Cite

New age patterns of survival improvement in Sweden: do they characterize changes in individual aging?

Journal Article Mechanisms of ageing and development · March 2002 The parameters of the Gompertz approximation to the mortality curve are negatively correlated. Strehler and Mildvan [Science 132 (1960) 14] predicted this property of the mortality curve using a mathematical model of mortality and aging and then confirmed ... Full text Cite

Heat shock changes the heterogeneity distribution in populations of Caenorhabditis elegans: does it tell us anything about the biological mechanism of stress response?

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · March 2002 In this paper we analyze survival data of populations of sterilized nematodes, Caenorhabditis elegans, exposed to heat shocks of different duration at the beginning of their adult lives. There are clear hormesis effects after short exposure to heat and cle ... Full text Cite

A centenarian-only approach for assessing gene-gene interaction in human longevity.

Journal Article European journal of human genetics : EJHG · February 2002 In this study, we introduce a centenarian-only approach to the assessment of gene-gene interaction that contributes to human longevity. This approach corresponds to the non-traditional case-only method in the genetic study of gene and disease associations. ... Full text Cite

Introduction

Chapter · 2002 Cite

Genetic analysis of cause of death in a mixture model of bivariate lifetime data

Journal Article Statistical Modeling · January 1, 2002 A mixture model in multivariate survival analysis is presented, whereby heterogeneity among subjects creates divergent paths for the individual’s risk of experiencing an event (i.e., disease), as well as for the associated length of survival. Dependence am ... Full text Cite

User interface design patterns for interactive modeling in demography and biostatistics

Conference Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) · January 1, 2002 The paper is focused on the interface design patterns for interactive modeling and it is an effort to systematically describe the usage of UID patterns in this area. Main objectives were to develop the UID patterns to increase the usability of the software ... Full text Cite

Detection of hormesis effect in longevity: simulation approach for heterogeneous population.

Journal Article Mathematical biosciences · January 2002 Manifestation of hormesis in longevity was modelled by modification of the mortality rate during and after the period of a stress factor action. In heterogeneous population this can lead to observation of unchanged mortality during action of the stress and ... Full text Cite

A model of accelerated aging induced by 5-bromodeoxyuridine.

Journal Article Biogerontology · January 2002 We consider a scheme of aging with two possible mechanisms of senescence processes: aging with apoptosis and necrosis for differentiated cells and a multistage process of malignant transformation. Our model describes the multistage phenomena of aging and c ... Full text Cite

A logistic regression model for measuring gene-longevity associations.

Journal Article Clinical genetics · December 2001 The logistic regression model is a popular model for data analysis in epidemiological research. In this paper, we use this model to analyze genetic data collected from gene-longevity association studies. This new approach models the probability of observin ... Full text Cite

Hormesis and debilitation effects in stress experiments using the nematode worm Caenorhabditis elegans: the model of balance between cell damage and HSP levels.

Journal Article Experimental gerontology · December 2001 In this article, we discuss mechanisms responsible for the effects of heat treatment on increasing subsequent survival in the nematode worm Caenorhabditis elegans. We assume that the balance between damage associated with exposure to thermal stress and the ... Full text Cite

The new trends in survival improvement require a revision of traditional gerontological concepts.

Journal Article Experimental gerontology · December 2001 In 1960, Strehler and Mildvan (SM) theoretically predicted that the parameters of the Gompertz approximation to a mortality curve are negatively correlated. This means that the changes in the human mortality rate resulting from improvement in living standa ... Full text Cite

Have the oldest old adults ever been frail in the past? A hypothesis that explains modern trends in survival.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · October 2001 Three important results concerning the shape and the trends of the human mortality rate were discussed recently in demographic and epidemiological literature. These are the deceleration of the mortality rate at old ages, the tendency to rectangularization ... Full text Cite

Cardiovascular mortality in twins and the fetal origins hypothesis.

Journal Article Twin research : the official journal of the International Society for Twin Studies · October 2001 The intrauterine growth patterns for twins are characterized by normal development during the first two trimesters and reduced growth during the third trimester. According to the fetal origins hypothesis this growth pattern is associated with risk factors ... Full text Cite

Ageing and survival after different doses of heat shock: the results of analysis of data from stress experiments with the nematode worm Caenorhabditis elegans.

Journal Article Mechanisms of ageing and development · September 2001 Stress experiments performed on a population of sterilised nematode worms (Caenorhabditis elegans) show a clear hormesis effect after short exposure and clear debilitation effects after long exposure to heat shock. An intermediate duration of exposure resu ... Full text Cite

How individual age-associated changes may influence human morbidity and mortality patterns.

Journal Article Mechanisms of ageing and development · September 2001 Patterns of human mortality share common traits in different populations. They include higher mortality in early childhood, lower mortality during the reproductive period, an accelerated increase of mortality near the end of the reproductive period, and de ... Full text Cite

Variations of cardiovascular disease associated genes exhibit sex-dependent influence on human longevity.

Journal Article Experimental gerontology · August 2001 This article investigates the relationship between the polymorphic variations in genes associated with cardiovascular disease and longevity in the Danish population. A new procedure that combines both demographic and the individual genetic information in d ... Full text Cite

The heritability of mortality due to heart diseases: a correlated frailty model applied to Danish twins.

Journal Article Twin research : the official journal of the International Society for Twin Studies · August 2001 Data of the Danish Twin Registry on monozygotic and dizygotic twins are used to analyse genetic and environmental influences on susceptibility to heart diseases for males and females, respectively. The sample includes 7955 like-sexed twin pairs born betwee ... Full text Cite

Recent advances in human gene-longevity association studies.

Journal Article Mechanisms of ageing and development · July 2001 This paper reviews the recent literature on genes and longevity. The influence of genes on human life span has been confirmed in studies of life span correlation between related individuals based on family and twin data. Results from major twin studies ind ... Full text Cite

Melatonin increases both life span and tumor incidence in female CBA mice.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · July 2001 From the age of 6 months until their natural deaths, female CBA mice were given melatonin with their drinking water (20 mg/l) for 5 consecutive days every month. Intact mice served as controls. The results of this study show that the consumption of melaton ... Full text Cite

Replication studies in longevity: puzzling findings in Danish centenarians at the 3'APOB-VNTR locus.

Journal Article Annals of human genetics · July 2001 In Danes we replicated the 3'APOB-VNTR gene/longevity association study previously carried out in Italians, by which the Small alleles (less than 35 repeats) had been identified as frailty alleles for longevity. In Danes, neither genotype nor allele freque ... Full text Cite

Mitochondrial DNA haplogroups and APOE4 allele are non-independent variables in sporadic Alzheimer's disease.

Journal Article Human genetics · March 2001 Allele epsilon4 of the nuclear APOE gene is a leading genetic risk factor for sporadic Alzheimer's disease (AD). Moreover, an allele-specific effect of APOE isoforms on neuronal cell oxidative death is known. Because of the role of the mitochondrial genome ... Full text Cite

Measuring the genetic influence in modulating the human life span: gene-environment interaction and the sex-specific genetic effect.

Journal Article Biogerontology · January 2001 New approaches are needed to explore the different ways in which genes affect the human life span. One needs to assess the genetic effects themselves, as well as gene-environment interactions and sex dependency. In this paper, we present a new model that c ... Full text Cite

Effect of synthetic thymic and pineal peptides on biomarkers of ageing, survival and spontaneous tumour incidence in female CBA mice.

Journal Article Mechanisms of ageing and development · January 2001 Fifty female CBA mice were injected s.c. either with 0.1 ml saline, or with synthetic thymic dipeptide Lys-Glu or with synthetic pineal tetrapeptide Ala-Glu-Asp-Gly both in a single dose of 0.1 microg/animal monthly for five consecutive days from the age o ... Full text Cite

A homeostatic model of oxidative damage explains paradoxes observed in earlier aging experiments: a fusion and extension of older theories of aging.

Journal Article Biogerontology · January 2001 The Rate of Living and the Threshold Theories of Aging are two contradicting approaches used to explain experimental facts about aging in fruit flies. In this paper we suggest an approach that unifies these theories and removes the contradiction. The appro ... Full text Cite

Heating stress patterns in Caenorhabditis elegans longevity and survivorship.

Journal Article Biogerontology · January 2001 Survival data from Caenorhabditis elegans strain TJ1060 (spe-9; fer-15) following brief exposure to 35 degrees C have been investigated. Three experiments with 3-day-old worms were conducted with heat duration ranging between 0 and 12 hours. A statisticall ... Full text Cite

Anticipation of oxidative damage decelerates aging in virgin female medflies: hypothesis tested by statistical modeling.

Journal Article Experimental gerontology · October 2000 Empirical analysis of survival data obtained from large samples of Mediterranean fruit flies shows that the trajectory of the mortality rate for virgin females departs from that for females maintained in mixed sex cages. It increases, decelerates, reaches ... Full text Cite

The network and the remodeling theories of aging: historical background and new perspectives.

Journal Article Experimental gerontology · September 2000 Two general theories, i.e. "the network theory of aging" (1989) and "the remodeling theory of aging" (1995), as well as their implications, new developments, and perspectives are reviewed and discussed. Particular attention has been paid to illustrate: (i) ... Full text Cite

Genetic and environmental influences on functional abilities in Danish twins aged 75 years and older.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · August 2000 BackgroundFunctional abilities vary widely among elderly persons. The determinants of this variation are probably multiple and include normal aging processes as well as disease expression. This study estimates the relative importance of genetic an ... Full text Cite

Genes and longevity: lessons from studies of centenarians.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · July 2000 In population studies of aging, the data on genetic markers are often collected for individuals from different age groups. The idea of such studies is to identify "longevity" or "frailty" genes by comparing the frequencies of genotypes in the oldest and in ... Full text Cite

Genetic nature of individual frailty: comparison of two approaches.

Journal Article Twin research : the official journal of the International Society for Twin Studies · March 2000 The traditional frailty models used in genetic analysis of bivariate survival data assume that individual frailty (and longevity) is influenced by thousands of genes, and that the contribution of each separate gene is small. This assumption, however, does ... Full text Cite

Multivariate frailty model with a major gene: Application to genealogical data

Journal Article Studies in Health Technology and Informatics · January 1, 2000 Multivariate survival models are shown to be appropriate for the analysis of the genetic and the environmental nature of a human life-span. Models which involve continuously distributed individual frailty, play an important role in the genetic analysis of ... Full text Cite

Mortality modeling: A review

Journal Article Mathematical Population Studies · January 1, 2000 Looking at survival in terms of biological indicators of aging has given rise to various models of mortality, some of which we review here. The most notable models are that of Strehler and Mildvan, which relates the force of mortality to the ability of org ... Full text Cite

Vitality index in survival modeling: how physiological aging influences mortality.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · January 2000 We investigated the relation of the age trajectory of physiological indicators of the average metabolic activity of organisms in a population to the age-specific population mortality rate. We show that a metabolic rate indicator (MRI) can be estimated usin ... Full text Cite

Dependent Hazards in Multivariate Survival Problems

Journal Article Journal of Multivariate Analysis · November 1, 1999 A new class of bivariate survival distributions is constructed from a given family of survival distributions. The properties of these distributions are analyzed. It is shown that the same bivariate survival function can be derived using two radically diffe ... Full text Cite

Genes, demography, and life span: the contribution of demographic data in genetic studies on aging and longevity.

Journal Article American journal of human genetics · October 1999 In population studies on aging, the data on genetic markers are often collected for individuals from different age groups. The purpose of such studies is to identify, by comparison of the frequencies of selected genotypes, "longevity" or "frailty" genes in ... Full text Cite

On the possibility of immune response control based on parameterization and a mathematical model of molecular cellular kinetics

Journal Article Russian Journal of Numerical Analysis and Mathematical Modelling · January 1, 1999 In this paper we attempt to show that it is possible to study an 'age-immune system-mortality' chain, using mathematical models of disease. We also give the results of parameterization of models of this type and formulate a problem of optimal control over ... Full text Cite

Half of the variation in susceptibility to mortality is genetic: findings from Swedish twin survival data.

Journal Article Behavior genetics · January 1999 Molecular epidemiological studies confirm tremendous variability in genetic and environmental susceptibility to disease and death for humans. This variability as well as the roles of genetic and environmental factors in susceptibility to death can be estim ... Full text Cite

Genetic factors in susceptibility to death: a comparative analysis of bivariate survival models.

Journal Article Journal of epidemiology and biostatistics · January 1999 BackgroundMolecular epidemiological studies of aging and longevity are focused on evaluating the effects of single genes on susceptibility to disease and death. The effects of all genetic factors on susceptibility can be evaluated from the analysi ... Cite

What difference does the dependence between durations make? Insights for population studies of aging.

Journal Article Lifetime data analysis · January 1999 The interpretation of age-specific changes in hazards, relative risks, genetic parameters and other indicators of aging calculated from data on related individuals should take into account the regularities of bivariate selection. Due to such selection the ... Full text Cite

How heritable is individual susceptibility to death? The results of an analysis of survival data on Danish, Swedish and Finnish twins.

Journal Article Twin research : the official journal of the International Society for Twin Studies · December 1998 Molecular epidemiological studies confirm a substantial contribution of individual genes to variability in susceptibility to disease and death for humans. To evaluate the contribution of all genes to susceptibility and to estimate individual survival chara ... Full text Cite

Gene/longevity association studies at four autosomal loci (REN, THO, PARP, SOD2).

Journal Article European journal of human genetics : EJHG · November 1998 The possibility that four loci (REN, THO, PARP, SOD2) are associated with longevity was explored by comparing the genotypic pools of subjects older than 100 years with those of younger subjects matched for sex and geographic area (northern and southern Ita ... Full text Cite

Biodemographic trajectories of longevity.

Journal Article Science · May 8, 1998 Old-age survival has increased substantially since 1950. Death rates decelerate with age for insects, worms, and yeast, as well as humans. This evidence of extended postreproductive survival is puzzling. Three biodemographic insights--concerning the correl ... Full text Link to item Cite

The genetic component of discrete disability traits: an analysis using liability models with age-dependent thresholds.

Journal Article Behavior genetics · May 1998 The presence of familial and genetic effects in the Activities-of-Daily-Life (ADL) data collected in the first wave of the 1995 Longitudinal Study of Aging of Danish Twins (LSADT) older than 75 is tested using multithreshold liability models of disability ... Full text Cite

Age-related changes of the 3'APOB-VNTR genotype pool in ageing cohorts.

Journal Article Annals of human genetics · March 1998 The analysis of seven different age cohorts (697 individuals from 10 to 109 years old) revealed age-related changes in the 3'APOB-VNTR genotype pool. By recoding the 3'APOB-VNTR alleles into three size-classes (small, S, 26-34 repeats; medium, M, 35-39 rep ... Full text Cite

Multistate models of postpartum infecundity, fecundability and sterility by age and parity: Methodological issues

Journal Article Mathematical Population Studies · January 1, 1998 How do hidden physiological processes influence estimates of fecundability and sterility? Does unobserved heterogeneity play a role in these estimates? To address these questions mathematical models of the reproductive process are needed. It is not well kn ... Full text Cite

Analyses of cohort mortality incorporating observed and unobserved risk factors

Journal Article Mathematical and Computer Modelling · April 1, 1997 Interventions to prevent disease and increase life expectancy are most effectively developed from data on pathways to disease and death. Unfortunately, most national data sets separate end-state information-i.e., cause-specific mortality-from pathway data ... Full text Cite

How frailty models can be used for evaluating longevity limits: taking advantage of an interdisciplinary approach.

Journal Article Demography · February 1997 In this paper we discuss an approach to the analysis of mortality and longevity limits when survival data on related individuals with and without observed covariates are available. The approach combines the ideas of demography and survival analysis with me ... Full text Cite

Evaluating partially observed survival histories: Retrospective projection of covariate trajectories

Journal Article Applied Stochastic Models and Data Analysis · January 1, 1997 The use of maximum likelihood methods in analysing times to failure in the presence of unobserved randomly changing covariates requires constrained optimization procedures. An alternative approach using a generalized version of the EM-algorithm requires sm ... Full text Cite

Effects of unobserved and partially observed covariate processes on system failure: A review of models and estimation strategies

Journal Article Statistical Science · January 1, 1997 Stochastically changing covariates may inuence survival. They may be observed, unobserved or partly observed. We review the properties of hazard models explicitly representing the effects of unobserved, and partially observed, stochastic covariates. Such m ... Full text Cite

[Mortality among twins after the age of six: the programming hypothesis versus the twin-method].

Journal Article Ugeskrift for laeger · December 1996 According to the foetal-origins hypothesis the risk of adult morbidity and mortality is heightened by intrauterine growth retardation. Twins, and in particular monozygotic twins, experience growth retardation in utero. A total of 8495 twin individuals born ... Cite

How long can humans live? Lower bound for biological limit of human longevity calculated from Danish twin data using correlated frailty model.

Journal Article Mechanisms of ageing and development · June 1995 How long can people live? Opinions of the researchers diverge and debates continue. Is there any systematic way to address this question? In this paper, we suggest an approach to the estimation of the biological limit of human longevity using survival data ... Full text Cite

A NEW APPROACH TO GENETIC-ANALYSIS OF DURATION DATA

Conference BEHAVIOR GENETICS · May 1, 1995 Link to item Cite

Mortality among twins after age 6: fetal origins hypothesis versus twin method.

Journal Article BMJ (Clinical research ed.) · February 1995 ObjectiveTo test the validity of the fetal origins hypothesis and the classic twin method.DesignFollow up study of pairs of same sex twins in which both twins survived to age 6.SettingDenmark.Subjects8495 twin individual ... Full text Cite

The effects of health histories on stochastic process models of aging and mortality.

Journal Article Journal of mathematical biology · January 1995 A model of human health history and aging, based on a multivariate stochastic process with both continuous diffusion and discrete jump components, is presented. Discrete changes generate non-Gaussian diffusion with time varying continuous state distributio ... Full text Cite

Correlated individual frailty: an advantageous approach to survival analysis of bivariate data.

Journal Article Mathematical population studies · January 1995 "We develop a new model of bivariate survival based on the notion of correlated individual frailty. We analyze the properties of this model and suggest a new approach to the analysis of bivariate data that does not require a parametric specification--but ... Full text Cite

Survival of related individuals: an extension of some fundamental results of heterogeneity analysis.

Journal Article Mathematical population studies · January 1995 "Many ideas in the analysis of heterogeneous mortality are based on the relationship between individual and observed hazard rates. This connection is established with the help of conditional averaging procedure: The observed risk of death at age x is calcu ... Full text Cite

Genetic analysis of durations: correlated frailty model applied to survival of Danish twins.

Journal Article Genetic epidemiology · January 1995 Population studies of changes in human morbidity and mortality require models which take into account the influence of genetic and environmental factors on life-related durations, such as age at onset of the disease or disability, age at death, etc. In thi ... Full text Cite

A multistate model of fecundability and sterility.

Journal Article Demography · August 1994 This paper develops a multistate hazards model for estimating fecundability and sterility from data on waiting times to conception. Important features of the model include separate sterile and nonsterile states, a distinction between preexisting sterility ... Full text Cite

A duality in aging: the equivalence of mortality models based on radically different concepts.

Journal Article Mechanisms of ageing and development · May 1994 Several alternative mortality models fit Swedish old-age mortality data equally well. The models build on two different concepts of the heterogeneity of individuals in a population. The first concept concerns fixed, genetic differences among individuals in ... Full text Cite

Modifications of the EM algorithm for survival influenced by an unobserved stochastic process

Journal Article Stochastic Processes and their Applications · January 1, 1994 Let Y=(Yt)t≥0) be an unobserved random process which influences the distribution of a random variable T which can be interpreted as the time to failure. When a conditional hazard rate corresponding to T is a quadratic function of covariates, Y, the margina ... Full text Cite

Hazard rate and observed covariates: a natural way of parametrization

Journal Article Stochastic Analysis and Applications · January 1994 Full text Cite

Methods for combining ancillary data in stochastic compartment models of cancer mortality: generalization of heterogeneity models.

Journal Article Mathematical population studies · January 1993 "We present a mortality model where nationally representative survey data on risk factor distributions are combined with data on cohort mortality rates to increase information, i.e., a fixed marginal risk factor distribution is combined with a cohort model ... Full text Cite

The propagation of uncertainty in human mortality processes operating in stochastic environments.

Journal Article Theoretical population biology · April 1989 This paper presents a model describing how the uncertainty due to influential exogenous processes combines with stochasticity intrinsic to physiological aging processes and propagates through time to generate uncertainty about the future physiological stat ... Full text Cite

Applications of Martingale methods

Journal Article Automation and Remote Control · 1989 Cite

Estimating hidden morbidity via its effect on mortality and disability.

Journal Article Statistics in medicine · January 1988 The applicability of the theory of partially observed finite-state Markov processes to the study of disease, morbidity, and disability is explored. A method is developed for the continuous updating of parameter estimates over time in longitudinal studies a ... Full text Cite

Age-specific mortality trends in France and Italy since 1900: period and cohort effects.

Journal Article European journal of population = Revue europeenne de demographie · November 1987 Full text Cite

Targeting lifesaving: demographic linkages between population structure and life expectancy.

Journal Article European journal of population = Revue europeenne de demographie · May 1987 Full text Cite

Debilitation's aftermath: stochastic process models of mortality.

Journal Article Mathematical population studies · January 1987 A stochastic differential equation model is developed to clarify the interaction of debilitation, recuperation, selection, and aging. The model yields various insights about the lingering mortality consequences of disasters such as wars, famines, and epid ... Full text Cite

A note on the conditioning of the survival probability on random information

Journal Article Stochastic Processes and their Applications · January 1, 1987 Full text Cite

Continuous-Time Adaptive Filtering

Journal Article IEEE Transactions on Automatic Control · January 1, 1986 This note establishes necessary and sufficient conditions for convergence of Bayesian parameter estimates in continuous-time adaptive Kalman filter with a denumerable or finite set of parameter values. Copyright © 1986 by The Institute of Electrical and El ... Full text Cite

Applications of the grade of membership technique to event history analysis: Extensions to multivariate unobserved heterogeneity

Journal Article Mathematical Modelling · January 1, 1986 Analyses of the event histories of social and service utilization processes are often difficult because of a lack of adequate theory to specify the distributional form of any latent heterogeneity [J. Heckman and B. Singer, The identifiability of the propor ... Full text Cite

Evaluating the effects of observed and unobserved diffusion processes in survival analysis of longitudinal data

Journal Article Mathematical Modelling · January 1, 1986 In biostatistical, epidemiological and demographic studies of human survival it is often necessary to consider the dynamics of physiological processes and their influences on observed mortality rates. The parameters of a stochastic covariate process can be ... Full text Cite

Dependent competing risks: a stochastic process model.

Journal Article Journal of mathematical biology · January 1986 Analyses of human mortality data classified according to cause of death frequently are based on competing risk theory. In particular, the times to death for different causes often are assumed to be independent. In this paper, a competing risk model with a ... Full text Cite

CONTINUOUS-TIME ADAPTIVE FILTERING.

Journal Article IEEE Transactions on Automatic Control · 1986 Necessary and sufficient conditions are established for convergence of Bayesian parameter estimators in a continuous-time adaptive Kalman filter with a denumerable or finite set of parameter values. ... Cite

Heterogeneity's ruses: some surprising effects of selection on population dynamics.

Journal Article The American statistician · August 1985 "As a cohort of people, animals, or machines ages, the individuals at highest risk tend to die or exit first. This differential selection can produce patterns of mortality for the population as a whole that are surprisingly different from the patterns for ... Full text Cite

Mortality and aging in a heterogeneous population: a stochastic process model with observed and unobserved variables.

Journal Article Theoretical population biology · April 1985 Various multivariate stochastic process models have been developed to represent human physiological aging and mortality. These efforts are extended by considering the effects of observed and unobserved state variables on the age trajectory of physiological ... Full text Cite

Marriage and fertility in China: a graphical analysis.

Journal Article Population & Development Review · January 1, 1985 Data from China's 1982 one-in-a-thousand fertility survey are used to construct contour maps of Chinese marriage and fertility. They offer a panoramic view of the interaction of age, period, and cohort variations. The maps display long-term trends over the ... Cite

Mortality in Italy: contours of a century of evolution.

Journal Article Genus · January 1985 The authors construct contour maps of Italian male and female mortality rates for ages 0-79 for the years 1870-1979 using life table data from published sources. The maps "display persistent global and prominent local patterns of mortality, simultaneously ... Cite

The deviant dynamics of death in heterogeneous populations.

Journal Article International Institute for Applied Systems Analysis, Research Report · December 1, 1983 The members of most populations gradually die off or drop out: people die, machines wear out, residents move out, etc. In many such aging populations, some members are more likely to die than others. Standard analytical methods largely ignore this heteroge ... Cite

EFFICIENT SOLUTION OF THE INTERPOLATION PROBLEM ON THE BASIS OF OBSERVATIONS OF JUMP PROCESSES.

Journal Article Problems of information transmission · January 1, 1983 The authors investigate the problem of interpolating a process with piecewise-continuous trajectories on the basis of observations of a multivariate point process. Equations are derived for the estimates and errors of direct and inverse interpolation in th ... Cite

The deviant dynamics of death in heterogeneous populations.

Journal Article International Institute for Applied Systems Analysis, Research Report · January 1, 1983 The members of most populations gradually die off or drop out: people die, machines wear out, residents move out, etc. In many such aging populations, some members are more likely to die than others. Standard analytical methods largely ignore this heteroge ... Cite

CONVERGENCE OF BAYESIAN ESTIMATIONS IN ADAPTIVE CONTROL SCHEMES.

Journal Article Ricerche di Automatica · October 1, 1982 This paper is devoted to the problem of finding strong consistency conditions for denumerable and uncountable sets of parameter values in the continuous time stochastic observation process. It turns out that the consistency property is often equivalent to ... Cite

Extrapolation of Conditionally-gaussian Processes from the Observations of Jump-type Processes.

Journal Article Izvestia vyssih ucebnyh zavedenij. Priborostroenie · July 1, 1982 Two types of extrapolation are considered: the direct and inverse. Mesh equations are obtained for the first and second conditional moments assuming the observability of a multivariable process with gaussian compensators and the non-observability of a cont ... Cite

ON CONSISTENT PARAMETER ESTIMATION IN ADAPTIVE FILTERING.

Journal Article Problems of control and information theory · January 1, 1981 The paper investigates the necessary and sufficient conditions for consistency of parameter estimates in adaptive Kalman filtering. The unknown parameter is assumed to dictate the evolution of both the observed and unobserved processes and to take on value ... Cite

CONSISTENCY OF BAYESIAN PARAMETER ESTIMATES IN ADAPTIVE KALMAN FILTERING.

Journal Article Automation and Remote Control · 1981 Cite

CONSISTENCY OF BAYESIAN PARAMETER ESTIMATION.

Journal Article Problems of information transmission · January 1, 1981 The consistency problem is investigated for estimates of the conditional expectation types for random variables with a countable set of values acording to observations of random processes in discrete time. Necessary and sufficient conditions for strong con ... Cite

MANAGEMENT PROBLEMS IN PUBLIC HEALTH.

Journal Article Automation and Remote Control · 1979 Cite

Synthesis of oligomeric π-allylic complexes on the basis of reactions of triisobutylaluminum with nickel and cobalt halides

Journal Article Bulletin of the Academy of Sciences of the USSR Division of Chemical Science · July 1, 1978 1. The reaction of NiCl2 and CoCl2 with Al(i-Bu)3 in the presence of small amounts of dienes has been studied. 2. The reaction of NiCl2 with Al(i-Bu)3 in the presence of a diene results in the formation of π-alkylnickel chlorides, in which the alkenyl liga ... Full text Cite

ESTIMATION OF THE CHARACTERISTICS OF RANDOM DISCONTINUOUS PROCESSES.

Journal Article Automation and Remote Control · 1976 Cite

ON CONSTRUCTIVE ALGORITHMS OF OPTIMAL NONLINEAR FILTERING - 2.

Journal Article Automation and Remote Control · 1975 Cite

CONSTRUCTIVE ALGORITHMS OF OPTIMAL NONLINEAR FILTERING - 1.

Journal Article Automation and Remote Control · 1975 Cite

CORRECTION PROBLEM IN THE PRESENCE OF COST OF OBSERVATIONS

Journal Article Avtomat i Telemekh · January 1, 1970 Optimal control of a Markovian step process is considered in the presence of observation cost. It is shown that the optimization procedure can be carried out by a method analogous to that described in Dynamic Programming and Markovian Processes by G. A. Ho ... Cite

Filtering of jump processes

Journal Article Avtomat i Telemekh · January 1, 1970 Formulas are derived for the a posteriori probabilities of a studied process. The methods developed may be considered a generalization of the methods based on the theory of conditional Markovian processes and developed for observing processes with continuo ... Cite

RELATIVE SEMI-INVARIANTS IN THE FILTERING OF PROCESSES WITH STEP COMPONENTS

Journal Article Avtomat i Telemekh · January 1, 1970 Algorithms for approximate determination of the optimum estimates are devised. Examples are given. ... Cite

Markov-process filtering when the observation noise varies spasmodically

Journal Article Radiophysics and Quantum Electronics · July 1, 1969 Full text Cite

DETECTING STEP-VARYING PARAMETERS OF MULTIDIMENSIONAL PROCESSES

Journal Article Avtomat i Telemekh · January 1, 1969 Optimal methods of filtering step-function processes are investigated. It is shown that an optimal filter must be nonlinear. A system of equations is derived which permits the detection of current values of step-varying components of multidimensional proce ... Cite

ON THE CHOICE OF OPTIMAL OBSERVATION PROCESS

Journal Article Akademiya Nauk, Izvestiya, Tekhnicheskaya Kibernetika · January 1, 1969 The choice of optimal observation process in a certain ensemble is investigated. It is shown that the solution of this problem reduces to the application of the maximum principle and subsequent solution of a boundary-value problem. ... Cite

FILTERING OF NONSTATIONARY PROCESSES TAKING OBSERVATIONAL COSTS INTO ACCOUNT

Journal Article Avtomatika i Telemekhanika · January 1, 1969 Paper considers optimal control of observation; it is shown that this problem leads to use of usual methods of optimization for controls and functionals which depend on a posteriori characteristics. ... Cite