The Mechanistic Target of Rapamycin (mTOR) Pathway as a Target of Anti-aging Therapies - The Role of Rapamycin and Its Analogs in the Regulation of Cellular Processes and Their Impact on Longevity

Sep 29, 2026

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Aging is a complex, multifactorial biological process that erodes homeostasis, accumulates molecular damage, and increases susceptibility to civilization diseases. Pharmacological strategies are being pursued to slow or partially reverse aging, with mTOR as one of the best-characterized lifespan regulators integrating metabolic, hormonal, and environmental signals. Inhibition of mTOR by rapamycin and analogs prolongs life in many animal models and improves age-related physiology. Preclinical and early human trial data suggest benefits for metabolism, heart function, cognition, immunity, and skin aging, supporting ongoing research on mTOR and autophagy for longevity and metabolic health.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

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Introduction And Background

mTOR signaling and longevity

Rapamycin mechanism of action

Rapamycin history and research milestones

Review began 11/18/2025 Review ended 11/28/2025 Published 12/05/2025 © Copyright 2025 Zerdka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0. , which permits unrestricted use , distribution , and reproduction in any medium , provided the original author and source are credited. DOI: 10.7759/cureus.98514 Open Access Review Article The Mechanistic Target of Rapamycin (mTOR) Pathway as a Target of Anti-aging Therapies: The Role of Rapamycin and Its Analogs in the Regulation of Cellular Processes and Their Impact on Longevity Julia Zerdka 1, Patryk Brasse 1, Mateusz Piszka 1, Eliza Kwapien 1, Maria Kubicka 2 , Jakub Bartkowski 3, Jan Banach 4, Hubert Dacyl 1, Aleksandra Owczarska 1 1. Medicine, Wojewódzki Szpital Specjalistyczny nr 5 im. św. Barbary, Sosnowiec, POL 2. Medicine, Samodzielny Publiczny Szpital Kliniczny im. Andrzeja Mielęckiego w Katowicach, Katowice, POL 3. Medicine, Miejskie Zakłady Opieki Zdrowotnej w Żorach, Żory, POL 4. Medicine, Szpital Powiatowy w Limanowej Imienia Miłosierdzia Bożego, Limanowa, POL Corresponding author: Julia Zerdka, [julia.zerdka@gmail.com](julia.zerdka@gmail.com) Abstract Aging of the body is a complex, multifactorial biological process, leading to a gradual loss of homeostasis, accumulation of molecular damage, and an increase in susceptibility to civilization diseases. In the face of a global aging population, pharmacological strategies are intensively sought that could slow down or partially reverse the aging process. One of the best-understood molecular pathways for regulating lifespan is the mechanistic target of rapamycin (mTOR) pathway, which integrates metabolic, hormonal, and environmental signals. Inhibition of mTOR, through the use of rapamycin and its analogs, consistently prolongs life in numerous animal models, improving age-related physiological functions. Preclinical evidence indicates that rapamycin prolongs the life of animals, improves metabolism, heart function, cognitive abilities, and immunity. In human clinical trials, low doses of rapamycin improve the immune response, reduce markers of skin aging, and are well tolerated. Rapamycin opens a new chapter in research into pharmacological slowing of aging. Understanding its effects on mTOR and autophagy could enable the development of effective interventions to support human longevity and metabolic health in the future, making these substances a promising direction for further research. Categories: Pharmacology, Geriatrics, Genetics Keywords: anti-aging medicine, healthspan, longevity medicine, mechanistic target of rapamycin, mtor inhibitors Introduction And Background Modern science is facing numerous challenges of fundamental importance for the future of humanity, starting from the climate crisis, through civilization diseases, to the problem of an aging population. Among these issues, longevity occupies a special place, understood not only as prolonging life, but above all as prolonging the period of biological vitality-healthspan. Aging remains one of the most complex and multifactorial biological processes, involving both the accumulation of molecular damage and the deregulation of homeostatic mechanisms at the cellular and systemic level [1] . Despite enormous progress in knowledge in the field of the biology of aging, the question of the possibility of deliberately slowing it down or even partially reversing it raises great hopes and is a hot topic not only in the scientific community but also in public opinion. Unfortunately, as is often the case with complex problems, the growing interest in the topic of longevity goes hand in hand with the search for simple answers. The emergence of simplistic narratives and the search for the "elixir of longevity " becomes a symbol of this tendency. This review aims to show the complexity of the topic of pharmacological modulation of aging. In recent decades, a numbe

FAQs

Why is aging considered a target for pharmacological modulation?

Aging is described as multifactorial and progressive, involving loss of homeostasis and accumulation of molecular damage, which increases vulnerability to civilization diseases. Pharmacological approaches are sought to slow or partially reverse these processes.

What role does the mTOR pathway play in regulating lifespan?

The mechanistic target of rapamycin (mTOR) pathway integrates metabolic, hormonal, and environmental signals and is presented as a key regulator of cellular growth, metabolism, and energy homeostasis. Inhibiting mTOR is linked with lifespan extension in animal models.

How does rapamycin affect cellular processes relevant to longevity?

Rapamycin forms a complex with FKBP12 to suppress mTOR kinase activity. This downregulates protein synthesis and anabolic metabolism while promoting autophagy, which supports maintenance and repair processes associated with longevity effects.

Sep 29, 2026

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