Scholars@Duke
Konstantin Arbeev

Konstantin Arbeev

Associate Research Professor in the Social Science Research Institute
Social Science Research Institute
ka29@duke.edu
Box 90420, Durham, NC 27708
2024 W. Main Street, Room A102F, Durham, NC 27705

Selected Publications

Basic Science and Pathogenesis.

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 2025 BackgroundAPOE4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), with a higher effect in females than in males. Identifying factors that may reduce the detrimental impact of APOE4 on AD is an important research objecti ... Full text Cite

Developing Topics.

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 2025 BackgroundAccumulating evidence points to a major role of compromised immunity in Alzheimer's Disease (AD). The MIR146a and COMT genes are both known for their involvement in immune responses, as well as in AD-related traits. COMT also regulates t ... Full text Cite

Developing Topics.

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 2025 BackgroundInfections and neuroinflammation are increasingly recognized as key contributors to the pathogenesis of Alzheimer's disease (AD). Emerging evidence suggests that the immune-regulating genes GDF15 and MIR146A are promising targets for dev ... Full text Cite

Public Health.

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 2025 BackgroundAlzheimer's disease (AD) likely results from a combination of genetic, environmental, and other factors. Accumulating evidence points to a role of infections in AD. Traffic-related air pollution (TRAP) and APOE4 are major risk factors fo ... Full text Cite

Public Health.

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 2025 BackgroundOur earlier study using Medicare-linked data found that vaccination against shingles was associated with ∼20% reduced risk of Alzheimer's disease (AD) later in life. Here, we investigated genotype-specific associations of the shingles va ... Full text Cite

Developing Topics.

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 2025 BackgroundAPOE4 and its proxy, rs2075650 (G) allele, are strongly associated with Alzheimer's disease (AD), though the mechanisms remain debated. APOE4 has also been linked to infection severity. Infections, including pneumonia, have, in turn, bee ... Full text Cite

Lower Hippocampal Volume Partly Mediates the Association Between rs6859 in the NECTIN2 Gene and Alzheimer's Disease: New Findings from Causal Mediation Analysis of ADNI Data.

Journal Article medRxiv · September 4, 2025 Infections may contribute to neurodegeneration, including Alzheimer's disease (AD). Polymorphism in the NECTIN2 gene has been linked to both AD and vulnerability to infections. We hypothesized that neurodegeneration may mediate the connection between this ... Full text Link to item Cite

Whole blood transcriptional signatures of age and survival identified in Long Life Family and Integrative Longevity Omics Studies.

Journal Article bioRxiv · July 18, 2025 BACKGROUND: Age is one of the major risk factors for a wide range of diseases. Nevertheless, some individuals can better cope with these changes and become centenarians. We hypothesize that their blood transcriptome may provide insights into the mechanisms ... Full text Link to item Cite

SNP rs6543176 is associated with extreme human longevity but increased risk for cancer.

Journal Article GeroScience · June 2025 Using whole-genome sequencing (WGS) might offer insights into rare genetic variants associated with healthy aging and extreme longevity (EL), potentially pointing to useful therapeutic targets. In this study, we conducted a genome-wide association study us ... Full text Cite

Methods for joint modeling of longitudinal omics data and time-to-event outcomes: applications to lysophosphatidylcholines in connection to aging and mortality in the Long Life Family Study.

Journal Article Aging · May 2025 Studying the relationships between longitudinal changes in omics variables and event risks requires specific methodologies for joint analyses of longitudinal and time-to-event outcomes. We applied two such approaches (joint models [JM], stochastic process ... Full text Cite

APOE4 and infectious diseases jointly contribute to brain glucose hypometabolism, a biomarker of Alzheimer's pathology: New findings from the ADNI.

Journal Article PloS one · January 2025 BackgroundImpaired brain glucose metabolism is a preclinical feature of neurodegenerative diseases such as Alzheimer's disease (AD). Infections may promote AD-related pathology. Therefore, we investigated the interplay between infections and APOE4 ... Full text Cite

Basic Science and Pathogenesis

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2024 BACKGROUND: Results of recent analyses indicate that axon demyelination may play an important role in AD pathology. The MBP gene encodes a myelin basic protein involved in axon myelination in the nervous system including the central nervous system. Polymor ... Full text Cite

Metabolite signatures of chronological age, aging, survival, and longevity.

Journal Article Cell reports · November 2024 Metabolites that mark aging are not fully known. We analyze 408 plasma metabolites in Long Life Family Study participants to characterize markers of age, aging, extreme longevity, and mortality. We identify 308 metabolites associated with age, 258 metaboli ... Full text Cite

APOE4 and Infectious Diseases Jointly Contribute to Brain Glucose Hypometabolism, a Biomarker of Alzheimer's Pathology: New Findings from the ADNI.

Journal Article medRxiv · October 1, 2024 BACKGROUND: Impaired brain glucose metabolism is a preclinical feature of neurodegenerative diseases such as Alzheimer's disease (AD). Infections may promote AD-related pathology. Therefore, we investigated the interplay between infections and APOE4, a str ... Full text Link to item Cite

Elevated blood glucose levels are associated with the progression of brain hypometabolism, and HDL-C and APOE4 add to this association.

Journal Article medRxiv · September 23, 2024 BACKGROUND: Brain glucose hypometabolism has consistently been found in neurodegenerative disorders, including Alzheimer's disease (AD). High blood glucose and HDL cholesterol (HDL-C) levels have also been linked to neurodegeneration and AD. However, there ... Full text Link to item Cite

Methods for joint modelling of longitudinal omics data and time-to-event outcomes: Applications to lysophosphatidylcholines in connection to aging and mortality in the Long Life Family Study.

Journal Article medRxiv · July 30, 2024 Studying relationships between longitudinal changes in omics variables and risks of events requires specific methodologies for joint analyses of longitudinal and time-to-event outcomes. We applied two such approaches (joint models [JM], stochastic process ... Full text Link to item Cite

Associations of infections and vaccines with Alzheimer's disease point to a role of compromised immunity rather than specific pathogen in AD.

Journal Article Experimental gerontology · June 2024 IntroductionDiverse pathogens (viral, bacterial, fungal) have been associated with Alzheimer's disease (AD) and related traits in various studies. This suggests that compromised immunity, rather than specific microbes, may play a role in AD by inc ... Full text Cite

Genome-Wide Epistatic Network Analyses of Semantic Fluency in Older Adults.

Journal Article International journal of molecular sciences · May 2024 Semantic fluency impairment has been attributed to a wide range of neurocognitive and psychiatric conditions, especially in the older population. Moderate heritability estimates on semantic fluency were obtained from both twin and family-based studies sugg ... Full text Cite

The SNP rs6859 in NECTIN2 gene is associated with underlying heterogeneous trajectories of cognitive changes in older adults.

Journal Article BMC neurology · February 2024 BackgroundFunctional decline associated with dementia, including in Alzheimer's disease (AD), is not uniform across individuals, and respective heterogeneity is not yet fully explained. Such heterogeneity may in part be related to genetic variabil ... Full text Cite

The Protective Effect of Familial Longevity Persists After Age 100: Findings From the Danish National Registers.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · January 2024 BackgroundA recent study suggested that the protective effect of familial longevity becomes negligible for centenarians. However, the authors assessed the dependence on familial longevity in centenarians by comparing centenarians with 1 parent sur ... Full text Cite

Patterns of Aging Changes in Bodyweight May Predict Alzheimer's Disease.

Journal Article J Alzheimers Dis · 2024 Relationships between patterns of aging-changes in bodyweight and AD are not fully understood. We compared mean age-trajectories of weight between those who did and did not develop late-onset-AD, and evaluated impact of age at maximum weight (AgeMax), and ... Full text Link to item Cite

How are APOE4, changes in body weight, and longevity related? Insights from a causal mediation analysis.

Journal Article Frontiers in aging · January 2024 The ε4 allele of the APOE gene (APOE4) is known for its negative association with human longevity; however, the mechanism is unclear. APOE4 is also linked to changes in body weight, and the latter changes were associated with survival in some ... Full text Cite

Prior infections are associated with smaller hippocampal volume in older women.

Journal Article Frontiers in dementia · January 2024 Accumulating evidence suggests that infections may play a major role in Alzheimer's disease (AD), however, mechanism is unclear, as multiple pathways may be involved. One possibility is that infections could contribute to neurodegeneration directly by prom ... Full text Cite

End of Life Events and Causes of Death in Danish Long-Lived Siblings: Reduced Dementia Risk Compared to Sporadic Long-Livers.

Journal Article Journal of Alzheimer's disease : JAD · January 2024 BackgroundBetter physical robustness and resilience of long-lived siblings compared to sporadic long-livers has been demonstrated in several studies. However, it is unknown whether long-lived siblings also end their lives better.Objective ... 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

Traffic-related air pollution and APOE4 can synergistically affect hippocampal volume in older women: new findings from UK Biobank.

Journal Article Frontiers in dementia · January 2024 A growing research body supports the connection between neurodegenerative disorders, including Alzheimer's disease (AD), and traffic-related air pollution (TRAP). However, the underlying mechanisms are not well understood. A deeper investigation of TRAP ef ... Full text Cite

The association between rs6859 in NECTIN2 gene and Alzheimer's disease is partly mediated by pTau.

Journal Article Frontiers in aging neuroscience · January 2024 IntroductionEmerging evidence suggests a connection between vulnerability to infections and Alzheimer's disease (AD). The nectin cell adhesion molecule 2 (NECTIN2) gene coding for a membrane component of adherens junctions is involved in re ... Full text Cite

Is being overweight a causal factor in better survival among the oldest old? a Mendelian randomization study.

Journal Article Frontiers in aging · January 2024 Overweight, defined by a body mass index (BMI) between 25 and 30, has been associated with enhanced survival among older adults in some studies. However, whether being overweight is causally linked to longevity remains unclear. To investigate this, we cond ... Full text Cite

Methionine restriction-induced sulfur deficiency impairs antitumour immunity partially through gut microbiota.

Journal Article Nature metabolism · September 2023 Restriction of methionine (MR), a sulfur-containing essential amino acid, has been reported to repress cancer growth and improve therapeutic responses in several preclinical settings. However, how MR impacts cancer progression in the context of the intact ... Full text Cite

Rare genetic variants correlate with better processing speed.

Journal Article Neurobiology of aging · May 2023 We conducted a genome-wide association study of Digit Symbol Substitution Test scores administered in 4207 family members of the Long Life Family Study (LLFS). Genotype data were imputed to the HRC panel of 64,940 haplotypes resulting in ∼15M genetic varia ... Full text Cite

Understanding Alzheimer's disease in the context of aging: Findings from applications of stochastic process models to the Health and Retirement Study.

Journal Article Mechanisms of ageing and development · April 2023 There is growing literature on applications of biodemographic models, including stochastic process models (SPM), to studying regularities of age dynamics of biological variables in relation to aging and disease development. Alzheimer's disease (AD) is espe ... Full text Cite

Forecasting prevalence and mortality of Alzheimer's disease using the partitioning models.

Journal Article Exp Gerontol · April 2023 OBJECTIVES: Health forecasting is an important aspect of ensuring that the health system can effectively respond to the changing epidemiological environment. Common models for forecasting Alzheimer's disease and related dementias (AD/ADRD) are based on sim ... Full text Link to item Cite

Exogenous exposures shape genetic predisposition to lipids, Alzheimer's, and coronary heart disease in the MLXIPL gene locus.

Journal Article Aging · April 2023 Associations of single nucleotide polymorphisms (SNPs) of the MLXIPL lipid gene with Alzheimer's (AD) and coronary heart disease (CHD) and potentially causal mediation effects of their risk factors, high-density lipoprotein cholesterol (HDL-C) and t ... Full text Cite

Interactions between genes involved in physiological dysregulation and axon guidance: role in Alzheimer's disease.

Journal Article Front Genet · 2023 Dysregulation of physiological processes may contribute to Alzheimer's disease (AD) development. We previously found that an increase in the level of physiological dysregulation (PD) in the aging body is associated with declining resilience and robustness ... Full text Link to item Cite

Vaccination Against Pneumonia May Provide Genotype-Specific Protection Against Alzheimer's Disease.

Journal Article J Alzheimers Dis · 2023 Vaccine repurposing that considers individual genotype may aid personalized prevention of Alzheimer's disease (AD). In this retrospective cohort study, we used Cardiovascular Health Study data to estimate associations of pneumococcal polysaccharide vaccine ... Full text Link to item Cite

APOE ɛ4 allele and TOMM40-APOC1 variants jointly contribute to survival to older ages.

Journal Article Aging cell · December 2022 Age-related diseases characteristic of post-reproductive life, aging, and life span are the examples of polygenic non-Mendelian traits with intricate genetic architectures. Polygenicity of these traits implies that multiple variants can impact their risks ... Full text Cite

A Genome-Wide Association Study of 2304 Extreme Longevity Cases Identifies Novel Longevity Variants.

Journal Article International journal of molecular sciences · December 2022 We performed a genome-wide association study (GWAS) of human extreme longevity (EL), defined as surviving past the 99th survival percentile, by aggregating data from four centenarian studies. The combined data included 2304 EL cases and 5879 controls. The ... Full text Cite

Physical resilience after a diagnosis of cardiovascular disease among offspring of long-lived siblings.

Journal Article European journal of ageing · September 2022 Health benefits of longevity-enriched families transmit across generations and a lower incidence of cardiovascular diseases (CVD) have been shown to contribute to this phenomenon. In the current study, we investigated whether the offspring of long-lived si ... Full text Cite

Genome-wide analysis of genetic predisposition to common polygenic cancers.

Journal Article Journal of applied genetics · May 2022 Lung, breast, prostate, and colorectal cancers are among the most common and fatal malignancies worldwide. They are mainly caused by multifactorial mechanisms and are genetically heterogeneous. We investigated the genetic architecture of these cancers thro ... Full text Cite

Telomere-length dependent T-cell clonal expansion: A model linking ageing to COVID-19 T-cell lymphopenia and mortality.

Journal Article EBioMedicine · April 2022 BackgroundSevere COVID-19 T-cell lymphopenia is more common among older adults and entails poor prognosis. Offsetting the decline in T-cell count during COVID-19 demands fast and massive T-cell clonal expansion, which is telomere length (TL)-depen ... Full text Cite

Evaluation of GENESIS, SAIGE, REGENIE and fastGWA-GLMM for genome-wide association studies of binary traits in correlated data.

Journal Article Frontiers in genetics · January 2022 Performing a genome-wide association study (GWAS) with a binary phenotype using family data is a challenging task. Using linear mixed effects models is typically unsuitable for binary traits, and numerical approximations of the likelihood function may not ... Full text Cite

Short Telomeres and a T-Cell Shortfall in COVID-19: The Aging Effect.

Journal Article medRxiv · July 10, 2021 UNLABELLED: The slow pace of global vaccination and the rapid emergence of SARS-CoV-2 variants suggest recurrent waves of COVID-19 in coming years. Therefore, understanding why deaths from COVID-19 are highly concentrated among older adults is essential fo ... Full text Link to item Cite

Interplay between stress-related genes may influence Alzheimer's disease development: The results of genetic interaction analyses of human data.

Journal Article Mechanisms of ageing and development · June 2021 Emerging evidence from experimental and clinical research suggests that stress-related genes may play key roles in AD development. The fact that genome-wide association studies were not able to detect a contribution of such genes to AD indicates the possib ... Full text Cite

Decline in biological resilience as key manifestation of aging: Potential mechanisms and role in health and longevity.

Journal Article Mechanisms of ageing and development · March 2021 Decline in biological resilience (ability to recover) is a key manifestation of aging that contributes to increase in vulnerability to death with age eventually limiting longevity even in people without major chronic diseases. Understanding the mechanisms ... Full text Cite

Interactions Between Genes From Aging Pathways May Influence Human Lifespan and Improve Animal to Human Translation.

Journal Article Frontiers in cell and developmental biology · January 2021 A major goal of aging research is identifying genetic targets that could be used to slow or reverse aging - changes in the body and extend limits of human lifespan. However, majority of genes that showed the anti-aging and pro-survival effects in animal mo ... Full text Cite

Roles of interacting stress-related genes in lifespan regulation: insights for translating experimental findings to humans.

Journal Article Journal of translational genetics and genomics · January 2021 AimExperimental studies provided numerous evidence that caloric/dietary restriction may improve health and increase the lifespan of laboratory animals, and that the interplay among molecules that sense cellular stress signals and those regulating ... Full text Cite

Physical robustness and resilience among long-lived female siblings: a comparison with sporadic long-livers.

Journal Article Aging · July 2020 Long-lived individuals are central in studies of healthy longevity. However, few pro-longevity factors have been identified, presumably because of "phenocopies", i.e. individuals that live long by chance. Familial longevity cases may include less phenocopi ... Full text Cite

Prevalence, Incidence, and Risk Factors for Overall, Physical, and Cognitive Independence Among Those From Exceptionally Long-Lived Families: The Long Life Family Study.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · April 2020 BackgroundThe Long Life Family Study (LLFS) enrolled families exhibiting exceptional longevity. The goal of this article was to determine the prevalence and predictors of remaining independent after 7 years in the oldest generation.Methods Full text Cite

Genetics of physiological dysregulation: findings from the long life family study using joint models.

Journal Article Aging · April 2020 Recently, Mahalanobis distance (DM) was suggested as a statistical measure of physiological dysregulation in aging individuals. We constructed DM variants using sets of biomarkers collected at the two visits of the Long Life Family St ... Full text Cite

APOE region molecular signatures of Alzheimer's disease across races/ethnicities.

Journal Article Neurobiology of aging · March 2020 The role of even the strongest genetic risk factor for Alzheimer's disease (AD), the apolipoprotein E (APOE) ε4 allele, in its etiology remains poorly understood. We examined molecular signatures of AD defined as differences in linkage disequilibrium patte ... Full text Cite

The impact of disregarding family structure on genome-wide association analysis of complex diseases in cohorts with simple pedigrees.

Journal Article Journal of applied genetics · February 2020 The generalized linear mixed models (GLMMs) methodology is the standard framework for genome-wide association studies (GWAS) of complex diseases in family-based cohorts. Fitting GLMMs in very large cohorts, however, can be computationally demanding. Also, ... Full text Cite

Association of Leukocyte Telomere Length With Mortality Among Adult Participants in 3 Longitudinal Studies.

Journal Article JAMA network open · February 2020 ImportanceLeukocyte telomere length (LTL) is a trait associated with risk of cardiovascular disease and cancer, the 2 major disease categories that largely define longevity in the United States. However, it remains unclear whether LTL is associate ... Full text Cite

Genetic and regulatory architecture of Alzheimer's disease in the APOE region.

Journal Article Alzheimer's & dementia (Amsterdam, Netherlands) · January 2020 IntroductionApolipoprotein E (APOE) ε2 and ε4 alleles encoded by rs7412 and rs429358 polymorphisms, respectively, are landmark contra and pro "risk" factors for Alzheimer's disease (AD).MethodsWe examined differences in linkage dis ... Full text Cite

Composite Measure of Physiological Dysregulation as a Predictor of Mortality: The Long Life Family Study.

Journal Article Frontiers in public health · January 2020 Biological aging results in changes in an organism that accumulate over age in a complex fashion across different regulatory systems, and their cumulative effect manifests in increased physiological dysregulation (PD) and declining robustness and resilienc ... Full text Cite

Composite Measures of Physical Fitness to Discriminate Between Healthy Aging and Heart Failure: The COmPLETE Study.

Journal Article Frontiers in physiology · January 2020 BackgroundAging and changing age demographics represent critical problems of our time. Physiological functions decline with age, often ending in a systemic process that contributes to numerous impairments and age-related diseases including heart f ... Full text Cite

Functional aging in health and heart failure: the COmPLETE Study.

Journal Article BMC cardiovascular disorders · July 2019 BackgroundCardiovascular (CV) diseases including heart failure are the leading causes of morbidity, with age being the primary risk factor. The combination of age-related organic functional impairment and reduced physical fitness can drastically i ... 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

Genetic heterogeneity of Alzheimer's disease in subjects with and without hypertension.

Journal Article GeroScience · April 2019 Alzheimer's disease (AD) is a progressive neurodegenerative disorder caused by the interplay of multiple genetic and non-genetic factors. Hypertension is one of the AD risk factors that has been linked to underlying pathological changes like senile plaques ... Full text Cite

"Physiological Dysregulation" as a Promising Measure of Robustness and Resilience in Studies of Aging and a New Indicator of Preclinical Disease.

Journal Article The journals of gerontology. Series A, Biological sciences and medical sciences · March 2019 Recently suggested novel implementation of the statistical distance measure (DM) for evaluating "physiological dysregulation" (PD) in aging individuals (based on measuring deviations of multiple biomarkers from baseline or normal physiological states) allo ... Full text Cite

Independent associations of TOMM40 and APOE variants with body mass index.

Journal Article Aging cell · February 2019 The TOMM40-APOE variants are known for their strong, antagonistic associations with Alzheimer's disease and body weight. While a stronger role of the APOE than TOMM40 variants in Alzheimer's disease was suggested, comparative contribution of the TOMM40-APO ... Full text Cite

Pleiotropic Meta-Analysis of Age-Related Phenotypes Addressing Evolutionary Uncertainty in Their Molecular Mechanisms.

Journal Article Frontiers in genetics · January 2019 Age-related phenotypes are characterized by genetic heterogeneity attributed to an uncertain role of evolution in establishing their molecular mechanisms. Here, we performed univariate and pleiotropic meta-analyses of 24 age-related phenotypes dealing with ... 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

Applying Stochastic Process Model to Imputation of Censored Longitudinal Data

Conference ACM Bcb 2018 Proceedings of the 2018 ACM International Conference on Bioinformatics Computational Biology and Health Informatics · August 15, 2018 Longitudinal data are widely used in medicine, demography, sociology and other areas. Incomplete observations in such data often confound the results of analysis. A plethora of data imputation methods have already been proposed to alleviate this problem. T ... 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

Strong impact of natural-selection-free heterogeneity in genetics of age-related phenotypes.

Journal Article Aging · March 2018 A conceptual difficulty in genetics of age-related phenotypes that make individuals vulnerable to disease in post-reproductive life is genetic heterogeneity attributed to an undefined role of evolution in establishing their molecular mechanisms. Here, we p ... Full text Cite

How Well Does the Family Longevity Selection Score Work: A Validation Test Using the Utah Population Database.

Journal Article Frontiers in public health · January 2018 The Family Longevity Selection Score (FLoSS) was used to select families for the Long Life Family Study (LLFS) but has never been validated in other populations. The goal of this paper is to validate how well the FLoSS-based selection procedure works in an ... Full text Cite

The APOE ε4 allele is associated with a reduction in FEV1/FVC in women: A cross-sectional analysis of the Long Life Family Study.

Journal Article PloS one · January 2018 IntroductionMurine studies have shown that apolipoprotein E modulates pulmonary function during development, aging, and allergen-induced airway disease. It is not known whether the polymorphic human APOE gene influences pulmonary function.Obje ... Full text 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

Stochastic Process Model and Its Applications to Analysis of Longitudinal Data

Conference Proceedings of the 8th ACM International Conference on Bioinformatics, Computational Biology,and Health Informatics · August 20, 2017 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

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

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

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

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

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

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

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 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

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

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

Health Effects and Medicare Trajectories: Population-Based Analysis of Morbidity and Mortality Patterns

Chapter · January 1, 2016 The tremendous research potential of U.S. Medicare data for evaluation of current, and forecasting of future, patterns of aging-related diseases among older U.S. adults remains largely unexplored. In this chapter, we present and discuss the results of a se ... Full text Cite

Medical Cost Trajectories and Onset of Age-Associated Diseases

Chapter · January 1, 2016 Aging-related deterioration in health impacts an important economic component: the medical costs associated with disease diagnosis and treatment. Because almost all U.S. residents aged 65+ years old are covered by the Medicare system, prediction of future ... Full text Cite

Factors That May Increase Vulnerability to Cancer and Longevity in Modern Human Populations

Chapter · January 1, 2016 Cancer incidence rates for all disease sites combined and life expectancy have increased over time in many countries around the world. These increases were concurrent with economic progress and the spread of the Western lifestyle. Overall cancer risk and l ... Full text 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

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

Causal effects of time-dependent treatments in older patients with non-small cell lung cancer.

Journal Article PLoS One · 2015 BACKGROUND: Treatment selection for elderly patients with lung cancer must balance the benefits of curative/life-prolonging therapy and the risks of increased mortality due to comorbidities. Lung cancer trials generally exclude patients with comorbidities ... Full text Open Access Link to item 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

Incidence Patterns of Breast Cancer among Women 35 and Younger at Diagnosis

Conference ANNALS OF SURGICAL ONCOLOGY · February 1, 2014 Link to item 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

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

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

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

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

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

Cancer Risk and Behavioral Factors, Comorbidities, and Functional Status in the US Elderly Population.

Journal Article ISRN oncology · January 2011 About 80% of all cancers are diagnosed in the elderly and up to 75% of cancers are associated with behavioral factors. An approach to estimate the contribution of various measurable factors, including behavior/lifestyle, to cancer risk in the US elderly po ... 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

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

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

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

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

DYNAMIC DETERMINANTS OF EXCEPTIONAL HEALTH AND LONGEVITY

Journal Article GERONTOLOGIST · October 1, 2009 Link to item 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

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

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

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 Journal of the American Geriatrics Society · 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 = ... 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

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

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

A decrease in the dose of the lgl tumor suppressor increases life span of Drosophila in stress and is related to the maternal effect.

Journal Article Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · January 2006 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

Frailty Index as a Major Indicator of Aging Processes and Mortality in Elderly: Results From Analyses of the National Long Term Care Survey Data

Journal Article · September 27, 2005 To better understand mortality change with age capturing the variability in individuals' rates of aging, we performed comprehensive analysis of statistical properties of a cumulative index of age-associated disorders (deficits), called a "frailty index" (F ... Open Access Link to item Cite

Age-Associated Disorders As A Proxy Measure Of Biological Age: Findings From the NLTCS Data

Journal Article · September 25, 2005 Background: The relative contribution of different aging-associated processes to the age phenotype may differ among individuals, creating variability in aging manifestations among age-peers. Capturing this variability can significantly advance understandin ... Open Access Link to item 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

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

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

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

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

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

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

A simulation study of different correlated frailty models and estimation strategies

Scholarly Edition Frailty models are becoming more and more popular in the area of multivariate survival analysis. In particular, shared frailty models are often used despite their limitations. To overcome the disadvantages of shared frailty models numerous correlated frail ... Cite