2015
DOI: 10.18632/aging.100724
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Abstract: Case control studies of nonagenarians and centenarians provide evidence that long-lived individuals do not differ in the rate of disease associated variants compared to population controls. These results suggest that an enrichment of novel protective variants, rather than a lack of disease associated variants, determine the genetic predisposition to exceptionally long lives. Using data from the Long Life Family Study (LLFS), we sought to replicate these findings and extend them to include a larger number of di… Show more

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Cited by 21 publications
(31 citation statements)
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References 35 publications
(40 reference statements)
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“…They are also consistent with those of the Long Life Family Study, where participants did not have fewer risk alleles in SNPs associated with AD, CVD and stroke, type 2 diabetes, or cancer when compared to their offspring and spouses [17] . Also, Sebastiani et al [18] did not find lower levels of disease-related alleles in whole-genome sequences of a man and a women aged over 114 years, and while exceptional longevity is influenced by the combined effects of many SNPs in a genetic signature, the overall abundance of risk alleles was not markedly different between centenarians and controls [19] .…”
Section: Discussionsupporting
confidence: 86%
See 1 more Smart Citation
“…They are also consistent with those of the Long Life Family Study, where participants did not have fewer risk alleles in SNPs associated with AD, CVD and stroke, type 2 diabetes, or cancer when compared to their offspring and spouses [17] . Also, Sebastiani et al [18] did not find lower levels of disease-related alleles in whole-genome sequences of a man and a women aged over 114 years, and while exceptional longevity is influenced by the combined effects of many SNPs in a genetic signature, the overall abundance of risk alleles was not markedly different between centenarians and controls [19] .…”
Section: Discussionsupporting
confidence: 86%
“…These two brothers, however, are exceptional in a number of ways: they are not only centenarians but are exceptionally healthy and free of common complex diseases, and they have a strong family history of longevity. These data add to a growing and important body of evidence from multiple studies [16][17][18][19]24] that the healthy longevity phenotype is not due to a lower burden of disease alleles. Instead, rare protective factors may underlie the genetic component of this desirable phenotype.…”
Section: Discussionmentioning
confidence: 59%
“…Similarly, the NECS performed a genome‐wide association study with 801 participants with exceptional longevity and found that they had just as many single nucleotide polymorphisms associated with diseases as are encountered in the general population . A LLFS genome‐wide association study reached the same conclusion . If particularly healthy behaviors and a relative lack of disease‐associated variants are not primarily responsible for the prolonged health spans observed in individuals with exceptional longevity, then one needs to consider the presence of longevity‐associated genetic variants, among other factors, that counter the effects of disease‐associated variants and mechanisms that cause aging.…”
Section: Discussionmentioning
confidence: 93%
“…27 A LLFS genome-wide association study reached the same conclusion. 28 If particularly healthy behaviors and a relative lack of disease-associated variants are not primarily responsible for the prolonged health spans observed in individuals with exceptional longevity, then one needs to consider the presence of longevityassociated genetic variants, among other factors, that counter the effects of disease-associated variants and mechanisms that cause aging. Genomic discoveries made in individuals with exceptional longevity delineate several mechanisms underlying exceptional longevity and healthy aging.…”
Section: Discussionmentioning
confidence: 99%
“…Several studies have shown that long-lived individuals do not appear to carry a substantially lower number of common-complex disease risk alleles compared to typical individuals (1)(2)(3). It may be that despite carrying risk alleles, they express the diseaserelated variants at a lower level.…”
Section: Introductionmentioning
confidence: 99%