MINI REVIEW article

Front. Aging

Sec. Aging, Metabolism and Redox Biology

Volume 6 - 2025 | doi: 10.3389/fragi.2025.1628187

This article is part of the Research TopicInsights in Aging, Metabolism and Redox Biology: 2024View all 7 articles

Rapamycin for longevity: the pros, the cons, and future perspectives

Provisionally accepted
  • School of Medicine, University of Maryland, Baltimore, United States

The final, formatted version of the article will be published soon.

Rapamycin, an antibiotic discovered in the 1970s from Streptomyces hygroscopicus on Easter Island (Rapanui), has become a critical tool in biomedical research. Initially recognized for its potent antifungal and immunosuppressive properties, rapamycin has recently gained significant attention for anti-aging therapy and seizure treatment via mTOR pathway inhibition. The mechanistic target of the rapamycin (mTOR) pathway is an evolutionarily conserved metabolic signaling cascade that regulates cell division, growth, and survival. There is growing evidence that mTOR pathway activity accelerates aging and the development of age-related diseases including cancer, atherosclerosis, diabetes, and declining immune function. Therefore physicians and 'biohackers' are using mTOR inhibition via rapamycin (and rapamycin analogs) off-label for prevention of age-related conditions despite not being widely recognized as a treatment by the broader clinical community. Currently, rapamycin (i.e., sirolimus and everolimus) is FDA approved for the prevention of transplant organ rejection and for anti-seizure therapy in Tuberous Sclerosis Complex (TSC; caused by variants in TSC1 or 2),we aim to summarize the mTOR pathway, the impact rapamycin has on the mTOR pathway, and the state of rapamycin use in the field of aging and longevity. Importantly, we will discuss the gaps in knowledge, pitfalls, and potential for the use of rapamycin to prevent aging/age-related disease and discuss the lessons learned from achieving FDA approval of evirolimus for TSC-related seizures after many years of off-label use.Aging is defined as an intrinsic, progressive decline in physiological function that increases

Keywords: aging1, sirolimus2, epilepsy3, Everolimus4, mTOR5

Received: 13 May 2025; Accepted: 05 Jun 2025.

Copyright: © 2025 Roark and Iffland II. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Philip Henry Iffland II, School of Medicine, University of Maryland, Baltimore, United States

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