HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging

  • Jazwinski S
  • Kim S
  • Dai J
 et al. 
  • 27

    Readers

    Mendeley users who have this article in their library.
  • 37

    Citations

    Citations of this article.

Abstract

The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity.

Author-supplied keywords

  • Haplotypes
  • Healthy aging profile
  • Lipotoxicity
  • Longevity genes
  • Population stratification

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • S. Michal Jazwinski

  • Sangkyu Kim

  • Jianliang Dai

  • Li Li

  • Xiuhua Bi

  • James C. Jiang

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free