Association between SIRT6 Methylation and Human Longevity in a Chinese Population
Association between SIRT6 Methylation and Human Longevity in a Chinese Population
复制标题
SIRT6 甲基化与中国人群长寿之间的关联。
DOI：
10.1159/000508832
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发表时间：
2020-11-25
影响因子：
1.7
通讯作者：
Qin, Jian
中科院分区：
文献类型：
--
作者：
Tang, Xu;Wei, Yi;Qin, Jian
背景：Sirtuin 6基因（SIRT6）是一种长寿基因，参与多种代谢途径，但SIRT6甲基化与长寿之间的关系尚未阐明。方法：我们对 129 名有长寿家族史的居民（其中一名父母、自己或年龄 >= 90 岁的兄弟姐妹）和 86 名没有特别长寿家族史的人进行了病例对照研究，以确定这种关联。通过 DNA 焦磷酸测序分析 SIRT6 启动子 CpG 位点的甲基化状态。 qRT-PCR 和 ELISA 用于估计 SIRT6 信使 RNA (mRNA) 水平和蛋白质含量。六个 CpG 位点 (P1-P6) 被鉴定为 SIRT6 启动子区域中的甲基化可变位置。结果：在P2和P5 CpG位点，长寿组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。对照组中 SIRT6 的 mRNA 和蛋白水平下降（p < 0.0001 和 p = 0.038）。 mRNA水平与P2位点（r(s) = -0.173，p = 0.011）和P5位点（r(s) = -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（r(s) = 0.136，p = 0.046），但与P2位点的甲基化率没有显着相关性。结论：SIRT6甲基化水平低可能是中国人长寿的潜在保护因素。
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 (r(s) = -0.173, p = 0.011) and P5 sites (r(s) = -0.207, p = 0.002). Furthermore, the protein content positively correlated with the methylation rate at the P5 site (r(s) = 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.