Sirtuin 1 (SIRT1) is an evolutionarily conserved mammalian homolog of yeast Sir2, overexpression of which has been shown to extend lifespan and delay age-related phenotypes in model organisms. To investigate the role of SIRT1 in healthy aging in humans, we performed comprehensive resequencing analysis of SIRT1 to identify all possible variants in the exons, exon-intron junctions, and 3.1kb proximal promoter region in 16 centenarians and 16 controls of Ashkenazi Jewish (AJ) population. Genotyping analysis of 19 common SIRT1 SNPs discovered to have minor allele frequency greater than 5% was performed in 213 AJ centenarians and 169 AJ controls and showed that their allele and genotype frequencies were not significantly different between centenarians and controls. Further association analysis of 5 tagSNPs (rs10997854, rs142194353, rs12778366, rs35706870, and rs932658) that capture all common SNP information across the SIRT1 gene region (r2 = 0.9) with lipid profile showed that 2 tagSNPs were significantly associated after multiple testing corrections; rs3758391 with large LDL (P = 0.0365) and large HDL (P = 0.0412) and rs142194353 with large HDL (P = 0.0035) and HDL size (P = 0.0033). Taken together, these results suggest that genetic variation in SIRT1 may contribute to healthy aging by affecting lipid profiles in humans but not to longevity.

• PMID: 25305471
• DOI full text
• PMC full text
• PubMed
• PubTator

Reference Type

Journal Article | Research Support, N.I.H., Extramural

Authors

Han J, Atzmon G, Barzilai N, Suh Y

Primary Lit For

Additional Lit For

Review For