The Critical Role of mTOR in Longevity and Aging Regulation

Research Topic Highlights

This collection of articles explores how the mechanistic Target of Rapamycin Complex 1 (mTORC1), a central regulator of nutrient signaling and metabolism, prominently influences aging, lifespan, obesity, and various chronic diseases. Central themes include the relationship between nutrient availability—particularly amino acids—and the activation of mTORC1, as well as the organism-wide physiological consequences of dietary restriction (DR) and pharmacological suppression of mTORC1 through compounds such as rapamycin. Studies presented here highlight tissue-specific manipulation of translational processes downstream of mTORC1 in model organisms, demonstrating tissue-dependent effects on lifespan, reproduction, and systemic energy homeostasis. The collection further explores the molecular mechanisms involving transcription factors like C/EBP-β LAP that mediate mTORC1's regulatory effects on metabolism and fat catabolism, unveiling their therapeutic potential in treating obesity and preventing age-related disorders. A significant interplay between stress responses, such as stress granules, and mTORC1 signaling in aging is also discussed, emphasizing the complexity of aging pathways regulated by molecular and cellular stress processes. Altogether, these studies underscore mTORC1's critical role in aging and aging-associated metabolic pathologies, highlighting nutrient signaling and stress responses as promising therapeutic targets.

Context and Scope

The conserved serine/threonine protein kinase mechanistic target of rapamycin (mTOR) integrates multiple extra- and intracellular inputs including nutrition and growth factors. Impairment of mTOR signaling has been implicated in many age-related disorders such as diabetes, cancer, and neurodegeneration as well as aging itself. The critical involvement of mTOR in aging was first revealed in invertebrate organisms, where depletion of mTOR components was shown to extend lifespan. Subsequent research has shown that pharmacological inhibition of mTOR using the drug rapamycin consistently increases lifespan in diverse organisms, and also promotes healthspan in mice. mTOR signaling regulates critical cellular processes including autophagy, cell growth, and protein translation, and targeting these pathways also controls aging and health in model organisms. Overall, mTOR signaling has emerged as a central node for longevity and aging regulation, and drugs to target mTOR as a means to treat age-related diseases are being actively explored by both industry and academia.

This Research Topic invites papers on the following topics – amongst other:
• Dietary and lifestyle interventions that regulate mTOR
• Novel pharmaceutical interventions in the mTOR signaling pathway
• Mechanisms of aging regulation by mTOR;
• mTOR signaling and the etiology of age-related diseases;
• Sex- and tissue-specific aspects of mTOR signaling;
• System analysis to identify additional mechanistic roles of mTOR inhibition;
• The use and development of mTOR inhibitors to promote lifespan;
• Intersection between rapamycin/mTOR inhibition and other interventional pathways of longevity;