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

## TL;DR

This study explores how sirtuin enzymes SIRT1, SIRT3, and SIRT6 relate to human longevity, focusing on sex and cardiovascular health differences.

## Contribution

The study provides a sex- and health-stratified analysis of sirtuin profiles in a longevity-enriched human cohort.

## Key findings

- Sirtuin profiles were measured in a longevity-enriched cohort stratified by sex and cardiovascular disease status.
- Protein and mRNA levels of SIRT1, SIRT3, and SIRT6 were quantified to assess their role in healthy aging.
- The study establishes a baseline for sirtuin translational control in human longevity and cardiovascular health.

## Abstract

Rapid demographic ageing is transforming economies and health systems, compelling WHO’s Healthy Ageing framework to prioritize the preservation of older adults’ functional autonomy and social engagement. Achieving this goal hinges on a deep understanding of the biological mechanisms of ageing—which reflect complex interactions between genetic predisposition, environment and lifestyle—since genetic factors play a modest role in reaching age 70 but become increasingly influential in extreme longevity. Identifying reliable molecular biomarkers is therefore critical for predicting health outcomes, guiding preventive strategies and developing targeted therapies. In this pilot study, we assayed the activity of sirtuin enzymes—master regulators of key aging processes: energy metabolism, genome stability and inflammatory homeostasis—to establish simple, predictive biomarkers and actionable intervention targets for sustaining functional autonomy across the lifespan.

Sirtuins (SIRT1–SIRT7) are NAD+-dependent deacetylases that link cellular energy status to chromatin maintenance, mitochondrial function and inflammatory 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 for SIRT1, SIRT3 and SIRT6 in buccal epithelial cells obtained from healthy young adults, middle/late-aged individuals and nonagenarians/centenarians residing in a longevity-enriched region of south-eastern Azerbaijan. The cohort comprised 23 participants, stratified by sex and cardiovascular disease (CVD) status (5 per sex/CVD subgroup). 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.