Association between SIRT6 Methylation and Human Longevity in a Chinese Population

Abstract

<b><i>Background:</i></b> <i>Sirtuin</i> 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. <b><i>Methods:</i></b> 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 <i>SIRT6</i> promoter CpG sites. qRT-PCR and ELISA were used to estimate the <i>SIRT6</i> messenger RNA (mRNA) levels and protein content. Six CpG sites (P1–P6) were identified as methylation variable positions in the <i>SIRT6</i> promoter region. <b><i>Results:</i></b> At the P2 and P5 CpG sites, the methylation rates of the longevity group were lower than those of the control group (<i>p</i> &#x3c; 0.001 and <i>p</i> = 0.009), which might be independent determinants of longevity. The mRNA and protein levels of <i>SIRT6</i> decreased in the control group (<i>p</i> &#x3c; 0.0001 and <i>p</i> = 0.038). The mRNA level negatively correlated with the methylation rates at the P2 (<i>r</i>_s = −0.173, <i>p</i> = 0.011) and P5 sites (<i>r</i>_s = −0.207, <i>p</i> = 0.002). Furthermore, the protein content positively correlated with the methylation rate at the P5 site (<i>r</i>_s = 0.136, <i>p</i> = 0.046) but showed no significant correlation with the methylation rate at the P2 site. <b><i>Conclusion:</i></b> The low level of <i>SIRT6</i> methylation may be a potential protective factor of Chinese longevity.