Molecular drivers of ageing and emerging longevity therapies

Ageing is a gradual, multifactorial process that leads to the deterioration of physical and mental health, increasing the risk of disease and eventually death. Indicators of ageing manifest at the molecular level, including genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, loss of proteostasis, and dysregulation of key signalling pathways such as the mechanistic target of rapamycin (mTOR) and insulin signalling. These molecular hallmarks of ageing are interconnected, amplifying one another over time. The resulting cellular stress triggers apoptosis or drives cells into a pathological state known as cellular senescence, in which they secrete inflammatory, pro-ageing factors. Consequently, there is a progressive decline in tissue function and regenerative capacity, accompanied by atrophy and stem cell exhaustion under a chronically inflamed microenvironment. Although functional decline with age is irreversible, research indicates it can be delayed. In this review, we discuss the hallmarks of ageing, conventional pharmacological interventions with demonstrated anti-ageing effects in cellular and animal models, and emerging therapeutic strategies being explored as ageing becomes increasingly recognized as a major risk factor for disease development.