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

Publication ,  Journal Article
Ukraintseva, S; Yashin, A; Arbeev, K; Kulminski, A; Akushevich, I; Wu, D; Joshi, G; Land, KC; Stallard, E
Published in: 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. Here we argue that trade-off-like and conditional effects of genes can play central role in this phenomenon and in determining longevity. Such effects may occur as result of: (i) antagonistic influence of gene on the development of different health disorders; (ii) change in the effect of gene on vulnerability to death with age (especially, from "bad" to "good"); (iii) gene-gene interaction; and (iv) gene-environment interaction, among other factors. A review of current knowledge provides many examples of genetic factors that may increase the risk of one disease but reduce chances of developing another serious health condition, or improve survival from it. Factors that may increase risk of a major disease but attenuate manifestation of physical senescence are also discussed. Overall, available evidence suggests that the influence of a genetic variant on longevity may be negative, neutral or positive, depending on a delicate balance of the detrimental and beneficial effects of such variant on multiple health and aging related traits. This balance may change with age, internal and external environments, and depend on genetic surrounding. We conclude that trade-off-like and conditional genetic effects are very common and may result in situations when a disease "risk allele" can also be a pro-longevity variant, depending on context. We emphasize importance of considering such effects in both aging research and disease prevention.

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Published In

Biogerontology

DOI

EISSN

1573-6768

ISSN

1389-5729

Publication Date

February 2016

Volume

17

Issue

1

Start / End Page

109 / 127

Related Subject Headings

  • Survival Rate
  • Risk Factors
  • Models, Genetic
  • Longevity
  • Humans
  • Gerontology
  • Genetic Variation
  • Genetic Predisposition to Disease
  • Gene Frequency
  • Alleles
 

Citation

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ICMJE
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Ukraintseva, S., Yashin, A., Arbeev, K., Kulminski, A., Akushevich, I., Wu, D., … Stallard, E. (2016). Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro-longevity variants. Biogerontology, 17(1), 109–127. https://doi.org/10.1007/s10522-015-9600-1
Ukraintseva, Svetlana, Anatoliy Yashin, Konstantin Arbeev, Alexander Kulminski, Igor Akushevich, Deqing Wu, Gaurang Joshi, Kenneth C. Land, and Eric Stallard. “Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro-longevity variants.Biogerontology 17, no. 1 (February 2016): 109–27. https://doi.org/10.1007/s10522-015-9600-1.
Ukraintseva S, Yashin A, Arbeev K, Kulminski A, Akushevich I, Wu D, et al. Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro-longevity variants. Biogerontology. 2016 Feb;17(1):109–27.
Ukraintseva, Svetlana, et al. “Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro-longevity variants.Biogerontology, vol. 17, no. 1, Feb. 2016, pp. 109–27. Epmc, doi:10.1007/s10522-015-9600-1.
Ukraintseva S, Yashin A, Arbeev K, Kulminski A, Akushevich I, Wu D, Joshi G, Land KC, Stallard E. Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro-longevity variants. Biogerontology. 2016 Feb;17(1):109–127.
Journal cover image

Published In

Biogerontology

DOI

EISSN

1573-6768

ISSN

1389-5729

Publication Date

February 2016

Volume

17

Issue

1

Start / End Page

109 / 127

Related Subject Headings

  • Survival Rate
  • Risk Factors
  • Models, Genetic
  • Longevity
  • Humans
  • Gerontology
  • Genetic Variation
  • Genetic Predisposition to Disease
  • Gene Frequency
  • Alleles