mTOR signaling in aging and longevity: therapeutic opportunities

Abstract

Aging is a complex biological process characterized by the gradual decline of physiological functions and an increased susceptibility to chronic diseases, including cancer, cardiovascular disorders, metabolic syndromes, and neurodegenerative conditions. Among the major molecular pathways associated with aging, the mechanistic target of rapamycin (mTOR) signaling pathway has emerged as a central regulator of cellular growth, metabolism, and longevity. mTOR integrates signals from nutrients, growth factors, and cellular energy status to regulate essential cellular processes such as protein synthesis, autophagy, stress response, and metabolic homeostasis.
This review explores the role of mTOR signaling in aging and age-related diseases by summarizing findings from recent experimental and clinical studies. Evidence suggests that dysregulated mTOR activity contributes to several hallmarks of aging, including cellular senescence, impaired autophagy, metabolic imbalance, mitochondrial dysfunction, and stem cell exhaustion. Persistent activation of mTOR has been strongly associated with the progression of age-related disorders, whereas controlled inhibition of mTOR signaling has been shown to extend lifespan and improve healthspan in various model organisms.
Several therapeutic and lifestyle-based interventions targeting mTOR have demonstrated promising anti-aging effects. Pharmacological agents such as rapamycin and its analogues regulate mTOR activity and delay the onset of aging-associated diseases. In addition, non-pharmacological strategies including calorie restriction, intermittent fasting, regular physical exercise, and natural bioactive compounds have shown potential in modulating mTOR signaling and improving metabolic health.
Recent advances in geroscience further highlight emerging approaches such as combination therapies targeting multiple longevity pathways, integration of senolytic strategies, and precision medicine-based interventions designed to personalize anti-aging treatments. Although preclinical findings are encouraging, further long-term clinical studies are required to evaluate the efficacy, safety, and translational potential of mTOR-targeted therapies. A deeper understanding of mTOR signaling in aging biology may contribute to the development of innovative therapeutic strategies for promoting healthy aging and preventing age-related diseases.

Keywords: Aging, mTOR signaling, longevity, autophagy, anti-aging therapeutics