Aging-Dependent Genetic and Epigenetic Alterations on SIRT6 Gene in Human In this study, we investigated the association between longevity and genetic and epigenetic alterations in SIRT6 gene which plays important roles in metabolism and life span. Isolated genomic DNAs from blood samples of 56 individuals (34 females and 22 males) were screened using 7 pairs of primers covering 7 exons of SIRT6 gene. Single-strand conformation polymorphism (SSCP) technique was performed for nucleotide variation analyses. We observed polymorphic band patterns for exonic regions 1, 2, and 5; but not for 3, 4, 6 or 7. 17.9% of the subjects retained a polymorphic band pattern for at least one of those exonic regions. The sequencing of those samples revealed 5 deletions, 3 insertions, and 7 single nucleotide variations (SNVs) on either the intronic or exonic sequence. However, we found no significant evidence of an association between observed single nucleotide polymorphisms and longevity. For epigenetic changes, the methylation levels of SIRT6 gene promoter were detected by real-time PCR analysis following bisulfite treatment of genomic DNA. While the results indicated 43.21% methylation in 0-19 age groups, this ratio is found to be increased up to 65.63% in 20-79 age groups, and decreased to %52.15 in 80-99 age groups.
