SIRT1/3/6 Landscape of Human Longevity: A Sex- and Health-Stratified Pilot Study

Sirtuins (SIRT1–SIRT7) are NAD⁺ dependent deacylases that link cellular energy status to chromatin maintenance, mitochondrial function and in-flammatory signaling. While modulation of SIRT1, SIRT3 and SIRT6 extends lifespan in model organisms, evidence in extreme age humans is scarce. We quantified protein and mRNA levels, and protein to mRNA ratios, of SIRT1, SIRT3 and SIRT6 in buccal epithelial cells from healthy young adults, middle aged individuals and nonagenarians/centenarians in a longevity enriched region of south eastern Azerbaijan, stratifying participants by sex and car-diovascular disease (CVD) status. This design allows us to: (1) define a baseline “sirtuin profile” of healthy longevity, (2) evaluate the impact of CVD as a prevalent age-related pathology, and (3) explore potential sex-specific modulation. These findings establish an initial human framework linking sirtuin translational control to healthy ageing and cardiovascular health.