Sirtuins and the Twelve Hallmarks of Ageing: A Framework for Understanding Ageing Processes and Targeted Intervention

Ageing is an innate phenomenon that has not been fully elucidated, despite increasing research on ageing in response to the worsening global ageing population. This demographic shift leads to profound ethical and social implications for human health, delineated by the twelve hallmarks of ageing. Sirtuins, a family of NAD+ - dependent enzymes, are key in the ageing process, thus have been more extensively studied in recent years. This review summarises the mechanisms and molecular pathways through which sirtuins modulate each hallmark of ageing and therefore influence ageing and the incidence of age-related illnesses. The mounting evidence of the close interaction between sirtuins and longevity pathways indicates sirtuins’ function as therapeutic targets for extending health span and life span. We further summarise interventions which target sirtuins to modulate age-related changes on the molecular, cellular, and systemic levels.