mTOR signaling in aging: from causality to geroprotective interventions and hallmark-level outcomes.

Abstract

The mechanistic target of rapamycin (mTOR) pathway is an important integrator of processes involved in aging and longevity, coordinating nutrient sensing, metabolic adaptation, and cellular stress responses. This review presents a three-section framework in which mTOR functions as a dynamic signaling hub coordinating multiple biological processes underlying the aging process. Evidence from genetic, experimental, and translational studies supports a causal role for mTOR signaling in lifespan regulation in model organisms, whereas human data remain predominantly associative but biologically consistent. mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) regulate distinct yet complementary aspects of cellular metabolism, proteostasis, autophagy, stress adaptation, and tissue homeostasis. Major geroprotective interventions-including autophagy activation, dietary interventions, physical activity, and senotherapeutics-partly converge on mTOR signaling but also engage parallel pathways. This adaptive regulation restores anabolic-catabolic balance, enhances stress resilience, and improves metabolic flexibility. Collectively, the available evidence identifies mTOR as an important integrative node linking multiple hallmarks of aging and diverse geroprotective interventions. Rather than representing a single therapeutic target, mTOR should be viewed as a context-dependent signaling hub which precise, tissue-specific modulation may promote healthy aging and support future geroscience-based interventions.