The association of the SIRT6 rs117385980 variant with frailty and longevity: an exploratory study

Frailty, a common geriatric syndrome, is characterized by diminished physiological reserves and heightens the risk of adverse health events, including falls, hospitalizations, and mortality. Prevalence of frailty is increasing in populations by age. Sirtuin 6 (SIRT6) plays a pivotal role in energy metabolism, inflammation, DNA repair, oxidative stress, and fibrosis. Despite numerous studies investigating the functions of SIRT6, the role of its genetic variations in frailty remains poorly understood. The aim of this study was to investigate the association between SIRT6 SNP rs117385980 (C > T) and frailty syndrome. This study included samples from a cohort of older adults in Birjand, Iran, comprising 227 subjects, aged 60-90 years divided according to frailty status. Allele and genotype frequencies of the SIRT6 rs117385980 variant were analyzed in all participants. Results of the study indicated the increased presence of non-frail and pre-frail individuals compared to the frail group. Among individuals aged 60-69, 70-79, and 80-90 years, the frequency of the heterozygous CT genotype demonstrated a declining trend with advancing age (p = 0.07). Our findings suggest that the presence of rs117385980 T allele was decreased in older subjects but increased with robustness suggesting a diverse effect. Further studies with larger sample sizes and Dates of death data are warranted to confirm these preliminary findings.