ArticleExperimental gerontology2012
Human longevity and variation in GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidant pathway genes: cross sectional and longitudinal studies.
Article in Experimental gerontology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 77 citations in OpenAlex.
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- UCP3 polymorphisms, hand grip performance and survival at old age: association analysis in two Danish middle aged and elderly cohorts.Mechanisms of ageing and development · 2012Trial
- Allele-specific splicing modulates protein isoforms and Alzheimer's risk.bioRxiv : the preprint server for biology · 2026Article
- A short-lived fish with long-lasting effects: hallmarks of aging inFrontiers in aging · 2025Review
- A CRISPR base editing approach for the functional assessment of telomere biology disorder-related genes in human health and aging.Biogerontology · 2024Article
- TXNRD1 drives the innate immune response in senescent cells with implications for age-associated inflammation.Nature aging · 2024Article
- Evolutionarily Conserved Role of Thioredoxin Systems in Determining Longevity.Antioxidants (Basel, Switzerland) · 2023Review
- Convergent genomics of longevity in rockfishes highlights the genetics of human life span variation.Science advances · 2023Article
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- Transforming L1000 profiles to RNA-seq-like profiles with deep learning.BMC bioinformatics · 2022Article
- A Novel Selenium Polysaccharide Alleviates the Manganese (Mn)-Induced Toxicity in Hep G2 Cells andInternational journal of molecular sciences · 2022Article
- Analysis of longevity in Chordata identifies species with exceptional longevity among taxa and points to the evolution of longer lifespans.Biogerontology · 2021Article
- Decline in biological resilience as key manifestation of aging: Potential mechanisms and role in health and longevity.Mechanisms of ageing and development · 2021Review
- NTHL1 in genomic integrity, aging and cancer.DNA repair · 2020Review
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- The goddess who spins the thread of life: Klotho, psychiatric stress, and accelerated aging.Brain, behavior, and immunity · 2019Article
- Longevity: Lesson from Model Organisms.Genes · 2019Review
- Genetic Pathways of Aging and Their Relevance in the Dog as a Natural Model of Human Aging.Frontiers in genetics · 2019Review
- The genetic component of human longevity: New insights from the analysis of pathway-based SNP-SNP interactions.Aging cell · 2018Article
- Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria.eLife · 2018Article
Corrections and comments
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Authors and funding
19 authors at 10 institutions in 5 countries.
Funding
Abstract
Here we explore association with human longevity of common genetic variation in three major candidate pathways: GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidants by investigating 1273 tagging SNPs in 148 genes composing these pathways. In a case-control study of 1089 oldest-old (age 92-93) and 736 middle-aged Danes we found 1 pro/antioxidant SNP (rs1002149 (GSR)), 5 GH/IGF-1/INS SNPs (rs1207362 (KL), rs2267723 (GHRHR), rs3842755 (INS), rs572169 (GHSR), rs9456497 (IGF2R)) and 5 DNA repair SNPs (rs11571461 (RAD52), rs13251813 (WRN), rs1805329 (RAD23B), rs2953983 (POLB), rs3211994 (NTLH1)) to be associated with longevity after correction for multiple testing. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes we found 2 pro/antioxidant SNPs (rs10047589 (TNXRD1), rs207444 (XDH)), 1 GH/IGF-1/INS SNP (rs26802 (GHRL)) and 3 DNA repair SNPs (rs13320360 (MLH1), rs2509049 (H2AFX) and rs705649 (XRCC5)) to be associated with mortality in late life after correction for multiple testing. When examining the 11 SNPs from the case-control study in the longitudinal data, rs3842755 (INS), rs13251813 (WRN) and rs3211994 (NTHL1) demonstrated the same directions of effect (p<0.05), while rs9456497 (IGF2R) and rs1157146 (RAD52) showed non-significant tendencies, indicative of effects also in late life survival. In addition, rs207444 (XDH) presented the same direction of effect when inspecting the 6 SNPs from the longitudinal study in the case-control data, hence, suggesting an effect also in survival from middle age to old age. No formal replications were observed when investigating the 11 SNPs from the case-control study in 1613 oldest-old (age 95-110) and 1104 middle-aged Germans, although rs11571461 (RAD52) did show a supportive non-significant tendency (OR=1.162, 95% CI=0.927-1.457). The same was true for rs10047589 (TNXRD1) (HR=0.758, 95%CI=0.543-1.058) when examining the 6 SNPs from the longitudinal study in a Dutch longitudinal cohort of oldest-old (age 85+, N=563). In conclusion, the present candidate gene based association study, the largest to date applying a pathway approach, not only points to potential new longevity loci, but also underlines the difficulties of replicating association findings in independent study populations and thus the difficulties in identifying universal longevity polymorphisms.
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