Association between SIRT6 Methylation and Human Longevity in a Chinese Population.

IF 1.3 4区医学 Q4 GENETICS & HEREDITY

Public Health Genomics Pub Date : 2020-01-01 Epub Date: 2020-11-25 DOI:10.1159/000508832

Xu Tang, Yi Wei, Jian Wang, Shiyi Chen, Jiansheng Cai, Jiexia Tang, Xia Xu, Bingshuang Long, Guoqi Yu, Zhiyong Zhang, Min He, Jian Qin

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引用次数: 3

Abstract

Background: Sirtuin 6 gene (SIRT6) is a longevity gene that is involved in a variety of metabolic pathways, but the relationship between SIRT6 methylation and longevity has not been clarified.

Methods: We conducted a case-control study on 129 residents with a family history of longevity (1 of parents, themselves, or siblings aged ≥90 years) and 86 individuals without a family history of exceptional longevity to identify the association. DNA pyrosequencing was performed to analyze the methylation status of SIRT6 promoter CpG sites. qRT-PCR and ELISA were used to estimate the SIRT6 messenger RNA (mRNA) levels and protein content. Six CpG sites (P1-P6) were identified as methylation variable positions in the SIRT6 promoter region.

Results: At the P2 and P5 CpG sites, the methylation rates of the longevity group were lower than those of the control group (p < 0.001 and p = 0.009), which might be independent determinants of longevity. The mRNA and protein levels of SIRT6 decreased in the control group (p < 0.0001 and p = 0.038). The mRNA level negatively correlated with the methylation rates at the P2 (rs = -0.173, p = 0.011) and P5 sites (rs = -0.207, p = 0.002). Furthermore, the protein content positively correlated with the methylation rate at the P5 site (rs = 0.136, p = 0.046) but showed no significant correlation with the methylation rate at the P2 site.

Conclusion: The low level of SIRT6 methylation may be a potential protective factor of Chinese longevity.

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中国人群中SIRT6甲基化与人类寿命的关系

背景:SIRT6基因(SIRT6)是一种参与多种代谢途径的长寿基因，但SIRT6甲基化与长寿的关系尚不清楚。方法:我们对129名有长寿家族史的居民(父母、自己或兄弟姐妹中有一人年龄≥90岁)和86名没有异常长寿家族史的个体进行病例对照研究，以确定两者之间的关联。DNA焦磷酸测序分析SIRT6启动子CpG位点的甲基化状态。采用qRT-PCR和ELISA检测SIRT6信使RNA (mRNA)水平和蛋白含量。6个CpG位点(P1-P6)被鉴定为SIRT6启动子区域的甲基化可变位置。结果:长寿组P2和P5 CpG位点的甲基化率低于对照组(p < 0.001和p = 0.009)，这可能是长寿的独立决定因素。对照组SIRT6 mRNA和蛋白水平降低(p < 0.0001和p = 0.038)。mRNA水平与P2位点(rs = -0.173, p = 0.011)和P5位点(rs = -0.207, p = 0.002)的甲基化率呈负相关。此外，蛋白质含量与P5位点的甲基化率呈正相关(rs = 0.136, p = 0.046)，而与P2位点的甲基化率无显著相关。结论:SIRT6甲基化水平低可能是中国人长寿的潜在保护因素。

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

Public Health Genomics 医学-公共卫生、环境卫生与职业卫生

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： ''Public Health Genomics'' is the leading international journal focusing on the timely translation of genome-based knowledge and technologies into public health, health policies, and healthcare as a whole. This peer-reviewed journal is a bimonthly forum featuring original papers, reviews, short communications, and policy statements. It is supplemented by topic-specific issues providing a comprehensive, holistic and ''all-inclusive'' picture of the chosen subject. Multidisciplinary in scope, it combines theoretical and empirical work from a range of disciplines, notably public health, molecular and medical sciences, the humanities and social sciences. In so doing, it also takes into account rapid scientific advances from fields such as systems biology, microbiomics, epigenomics or information and communication technologies as well as the hight potential of ''big data'' for public health.