ArticlePloS one2014
SIRT6 minor allele genotype is associated with >5-year decrease in lifespan in an aged cohort.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed.
- The association of the SIRT6 rs117385980 variant with frailty and longevity: an exploratory study.Scientific reports · 2025Article
- Article
- Trajectories of cardiovascular ageing-from molecular mechanisms to clinical implementation.Cardiovascular research · 2025Review
- Article
- A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A.The EMBO journal · 2022Article
- Genetic regulation of newborn telomere length is mediated and modified by DNA methylation.Frontiers in genetics · 2022Article
- Sirtuin 6: linking longevity with genome and epigenome stability.Trends in cell biology · 2021Review
- The Role of Oxidative Stress in Cardiovascular Aging and Cardiovascular Diseases.Life (Basel, Switzerland) · 2021Review
- Age-related epigenetic drift deregulatesEpigenetics · 2020Article
- Biological and catalytic functions of sirtuin 6 as targets for small-molecule modulators.The Journal of biological chemistry · 2020Review
- Metabolic Communication and Healthy Aging: Where Should We Focus Our Energy?Developmental cell · 2020Review
- SIRT6, a Mammalian Deacylase with Multitasking Abilities.Physiological reviews · 2020Review
- Review
- Genetic and epigenetic regulation of human aging and longevity.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
- Analysis of Polymorphisms in 59 Potential Candidate Genes for Association With Human Longevity.The journals of gerontology. Series A, Biological sciences and medical sciences · 2018Article
- Genetic cartography of longevity in humans and mice: Current landscape and horizons.Biochimica et biophysica acta. Molecular basis of disease · 2018Review
- Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology.Critical reviews in biochemistry and molecular biology · 2018Review
- The Role of Sirtuins in Antioxidant and Redox Signaling.Antioxidants & redox signaling · 2018Review
- Identification and characterization of two functional variants in the human longevity gene FOXO3.Nature communications · 2017Article
- Sirtuin 3 deficiency does not alter host defenses against bacterial and fungal infections.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Aging is a natural process involving complex interplay between environment, metabolism, and genes. Sirtuin genes and their downstream targets have been associated with lifespan in numerous organisms from nematodes to humans. Several target proteins of the sirtuin genes are key sensors and/or effectors of oxidative stress pathways including FOXO3, SOD3, and AKT1. To examine the relationship between single nucleotide polymorphisms (SNP) at candidate genes in these pathways and human lifespan, we performed a molecular epidemiologic study of an elderly cohort (≥65 years old.). Using age at death as a continuous outcome variable and assuming a co-dominant genetic model within the framework of multi-variable linear regression analysis, the genotype-specific adjusted mean age at death was estimated for individual SNP genotypes while controlling for age-related risk factors including smoking, body mass index, alcohol consumption and co-morbidity. Significant associations were detected between human lifespan and SNPs in genes SIRT3, SIRT5, SIRT6, FOXO3 and SOD3. Individuals with either the CC or CT genotype at rs107251 within SIRT6 displayed >5-year mean survival advantages compared to the TT genotype (5.5 and 5.9 years, respectively; q-value = 0.012). Other SNPs revealed genotype-specific mean survival advantages ranging from 0.5 to 1.6 years. Gender also modified the effect of SNPs in SIRT3, SIRT5 and AKT1 on lifespan. Our novel findings highlight the impact of sirtuins and sirtuin-related genotypes on lifespan, the importance of evaluating gender and the advantage of using age as a continuous variable in analyses to report mean age at death.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.