Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Aging Cell. 2010 Oct;9(5):698-708. doi: 10.1111/j.1474-9726.2010.00600.x. Epub 2010 Aug 4.

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

Author information

  • 1Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA. sjazwins@tulane.edu

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.

© 2010 The Authors Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

PMID:
20569235
[PubMed - indexed for MEDLINE]
PMCID:
PMC2941558
Free PMC Article

Images from this publication.See all images (5)Free text

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Blackwell Publishing Icon for PubMed Central
    Loading ...
    Write to the Help Desk