ArticleAging cell2010
HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging.
Article in Aging cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
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- Feature Selection Algorithms Enhance the Accuracy of Frailty Indexes as Measures of Biological Age.The journals of gerontology. Series A, Biological sciences and medical sciences · 2021Article
- Lipid metabolism and lipid signals in aging and longevity.Developmental cell · 2021Review
- APOE region molecular signatures of Alzheimer's disease across races/ethnicities.Neurobiology of aging · 2020Article
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- Sphingolipids and their metabolism in physiology and disease.Nature reviews. Molecular cell biology · 2018Review
- Ras signaling in aging and metabolic regulation.Nutrition and healthy aging · 2017Review
- Epistasis, physical capacity-related genes and exceptional longevity: FNDC5 gene interactions with candidate genes FOXOA3 and APOE.BMC genomics · 2017Article
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 1 country.
Funding
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.
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