Xu Tang1,2, Yi Wei1, Jian Wang1, Shiyi Chen1, Jiansheng Cai1, Jiexia Tang1, Xia Xu1, Bingshuang Long1, Guoqi Yu1, Zhiyong Zhang1,3, Min He4, Jian Qin1,5. 1. Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, China. 2. Department of General Medicine, Affiliated Hospital of Guilin Medical University, Guilin, China. 3. Department of Occupational and Environmental Health, School of Public Health, Guilin Medical University, Guilin, China. 4. Department of Occupational and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, China, hemin@gxmu.edu.cn. 5. The First People's Hospital of Nanning, Nanning, China.
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.
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.
Authors: Chenglong Yu; Allison M Hodge; Ee Ming Wong; Jihoon Eric Joo; Enes Makalic; Daniel Schmidt; Daniel D Buchanan; John L Hopper; Graham G Giles; Melissa C Southey; Pierre-Antoine Dugué Journal: Cells Date: 2021-12-01 Impact factor: 6.600