The role of longevity-related genetic variant interactions as predictors of survival after 85 years of age

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development Pub Date : 2024-03-13 DOI:10.1016/j.mad.2024.111926

Maja Šetinc , Željka Celinšćak , Luka Bočkor , Matea Zajc Petranović , Anita Stojanović Marković , Marijana Peričić Salihović , Joris Deelen , Tatjana Škarić-Jurić

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引用次数: 0

Abstract

Genome-wide association studies and candidate gene studies have identified several genetic variants that might play a role in achieving longevity. This study investigates interactions between pairs of those single nucleotide polymorphisms (SNPs) and their effect on survival above the age of 85 in a sample of 327 Croatian individuals. Although none of the SNPs individually showed a significant effect on survival in this sample, 14 of the 359 interactions tested (between SNPs not in LD) reached the level of nominal significance (p<0.05), showing a potential effect on late-life survival. Notably, SH2B3 rs3184504 interacted with different SNPs near TERC, TP53 rs1042522 with different SNPs located near the CDKN2B gene, and CDKN2B rs1333049 with different SNPs in FOXO3, as well as with LINC02227 rs2149954. The other interaction pairs with a possible effect on survival were FOXO3 rs2802292 and ERCC2 rs50871, IL6 rs1800795 and GHRHR rs2267723, LINC02227 rs2149954 and PARK7 rs225119, as well as PARK7 rs225119 and PTPN1 rs6067484. These interactions remained significant when tested together with a set of health-related variables that also had a significant effect on survival above 85 years. In conclusion, our results confirm the central role of genetic regulation of insulin signalling and cell cycle control in longevity.

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与长寿相关的遗传变异相互作用对 85 岁后存活率的预测作用。

全基因组关联研究和候选基因研究发现了一些可能在实现长寿中发挥作用的基因变异。本研究以 327 名克罗地亚人为样本，调查了这些单核苷酸多态性（SNPs）之间的相互作用及其对 85 岁以上存活率的影响。虽然在该样本中，没有一个 SNPs 单独对存活率有显著影响，但在测试的 359 个相互作用中，有 14 个（不在 LD 中的 SNPs 之间）达到了名义显著性水平（p

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mechanisms of Ageing and Development 医学-老年医学

CiteScore

11.10

自引率

1.90%

发文量

审稿时长

32 days

期刊介绍： Mechanisms of Ageing and Development is a multidisciplinary journal aimed at revealing the molecular, biochemical and biological mechanisms that underlie the processes of aging and development in various species as well as of age-associated diseases. Emphasis is placed on investigations that delineate the contribution of macromolecular damage and cytotoxicity, genetic programs, epigenetics and genetic instability, mitochondrial function, alterations of metabolism and innovative anti-aging approaches. For all of the mentioned studies it is necessary to address the underlying mechanisms. Mechanisms of Ageing and Development publishes original research, review and mini-review articles. The journal also publishes Special Issues that focus on emerging research areas. Special issues may include all types of articles following peered review. Proposals should be sent directly to the Editor-in-Chief.