Association between SIRT6 Methylation and Human Longevity in a Chinese Population

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.

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.

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.

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