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Dr. Alpana Mohta Ranka, MD, DNB, IFAAD, is a dual-board-certified dermatologist with over 90 research publications in peer-reviewed scientific journals.

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Topical Rapamycin for Aging Skin – What You Need to Know?

Updated: 10 hours ago

What do Brian Johnson and David Sinclair have in common, aside from their immense wealth and unorthodox approaches to reversing aging? Both have reported turned to rapamycin, a drug initially intended to prevent organ transplant rejection, now being explored for its potential anti-aging properties. This is yet another example of serendipity in medicine - finding one thing while looking for something else.


A metaphorical image showing a damaged DNA strand being rejuvenated

What is Rapamycin?

Discovered in a soil sample from Easter Island in the 1970s, rapamycin (also known as 'sirolimus') was originally approved by the FDA in 1999 for use in organ transplants to prevent rejection. The drug’s ability to inhibit the mTOR pathway makes it a worthy contender in the anti-aging arena.



The mTOR Pathway and Autophagy

The mTOR pathway, short for "mechanistic target of rapamycin," is essential in regulating cell growth and metabolism and plays a central role in aging.


Over the past two centuries, human life expectancy has increased, largely due to advancements in medical and biological sciences. However, the increase in lifespan has not necessarily been accompanied by an extension of 'health span'—the period during which an individual remains free from age-related diseases.


Research suggests that while people are living longer, they continue to face age-related illnesses like cardiovascular diseases, type 2 diabetes, and Alzheimer's disease.


Wonder why? Well, overactivating mTOR speeds up aging and ups the chance of getting those diseases. How? By inhibiting autophagy, a cellular cleanup process, and promoting excessive cell growth.


Drugs like rapamycin that inhibit this pathway can slow the aging process and improve 'healthspan' by promoting better cellular maintenance.


Rapamycin's Role in Slowing Down Aging

Investigations into rapamycin's ability to delay aging began with findings published in 2006 by Dr. Mikhail Blagosklonny, a cellular aging researcher at the Roswell Park Comprehensive Cancer Center. Subsequent research from Novartis in collaboration with Stanford University further supported these findings, showing rapamycin's capacity to reduce age-related deterioration.


A pivotal study by the Max Planck Institute for Biology of Ageing demonstrated that short-term rapamycin treatment in early adulthood could impart long-lasting protective effects against aging in fruit flies and mice, particularly in maintaining gut health and integrity.


Topical Rapamycin

Topical Rapamycin has been successfully used to manage facial angiofibromas, acanthosis nigricans, and even psoriasis. However, its role as an antiaging modality remains largely unexplored.


A 2019 study by Drexel University College of Medicine examined Rapamycin cream's potential for rejuvenating aging skin in individuals over 40. Participants applied either Rapamycin or a placebo to one hand every other day for eight months. Skin biopsies and high-resolution photos revealed reduced aging markers, improved collagen structure, and more organized cellular arrangement in Rapamycin-treated skin. mRNA analysis suggested the treated skin appeared younger, with reduced wrinkles, increased skin thickness, and improved pigmentation and brightness.


While these findings are promising, translating these benefits to broader clinical applications remains challenging due to limited research on topical rapamycin for antiaging.

Could Tretinoin Be an Ally to Rapamycin?

So far, tretinoin currently holds the strongest evidence-supported research for its efficacy as a topical anti-aging treatment. What's interesting is that these two treatments operate through entirely different mechanisms. Tretinoin primarily works by promoting cell turnover and stimulating collagen synthesis, while rapamycin affects autophagy and intracellular trafficking of vesicles.


Moreover, based on several studies, topical rapamycin seems to be generally well tolerated with minimal adverse events. The common side effects, such as dryness and skin irritation, can very well be managed with proper moisturization.


In my opinion, as research into topical rapamycin progresses, it would be interesting to see how these two drugs perform when used together.


Looking Ahead

Rapamycin remains a largely understudied molecule for its topical benefits. Despite concerns, topical rapamycin may become widespread if regulatory barriers are overcome, sparking debate over its prescription status.


In the future, when (and if) rapamycin is granted approval for topical usage as prescription-grade skincare, Dr. Mikhail V. Blagosklonny suggests using rapamycin cream on specific skin areas, like hands and faces rather than on the whole body, for age-related issues.


Although systemic rapamycin could be better for slowing down aging, as skin aging often stems from systemic factors, topical application would be safer than systemic use. Combining both methods could be beneficial for targeted skin areas with aging signs.

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