As life expectancy continues to rise, the prevalence of chronic age-related diseases is also increasing, with individuals experiencing an average of 11 years of poor health [1]. This emphasizes the immediate need for research focused on the aging process itself.
A drug initially developed as an antifungal agent, rapamycin has emerged as a promising geroprotector – a compound capable of slowing the aging process and delaying the onset of multiple age-related diseases.
Rapamycin works by inhibiting the mechanistic target of the rapamycin (mTOR) pathway, a key regulator of the aging process. Animal studies have shown that decreased mTOR signaling can extend lifespan by up to 60% in mice [1].
But how does this translate to human health and longevity?
Boosting the immune system
One of the hallmarks of aging is a decline in immune function, known as immunosenescence.
Interestingly, randomized controlled trials have demonstrated that administering rapamycin derivatives, such as everolimus and RTB101, can significantly boost the immune response to seasonal influenza vaccines, particularly in older adults.
This effect is mediated by rapamycin’s ability to reverse certain aspects of immunosenescence.
For example, rapamycin treatment has decreased the number of PD-1-positive CD4 and CD8 T cells, which are associated with immune exhaustion.
Rapamycin has also been found to reduce the secretion of the anti-inflammatory cytokine IL-10 by stimulating immune cells, potentially enhancing their pro-inflammatory and antiviral responses [1].
These findings suggest that rapamycin and its derivatives could help maintain a more youthful and robust immune system, potentially reducing the risk of infectious diseases and improving vaccine efficacy in older adults.
Cardiovascular benefits
Aging is a significant risk factor for increased cardiovascular disease risk, including atherosclerosis and cardiac hypertrophy. It’s worth noting that rapamycin and its derivatives have positively impacted the cardiovascular system.
In a study of individuals with pulmonary hypertension, treatment with the rapamycin derivative everolimus resulted in a non-significant increase in 6-minute walk distance, a measure of cardiovascular fitness [1].
Additionally, ongoing clinical trials are investigating the effects of rapamycin on other cardiovascular parameters, such as aortic cross-sectional area, aortic distensibility, and peripheral insulin sensitivity.
These findings suggest that rapamycin and its derivatives may improve cardiovascular health and function, reducing the risk of age-related cardiovascular diseases.
Skin health and appearance
The aging process also affects the skin, the body’s largest organ. Rapamycin has been shown to have beneficial effects on skin health and appearance.
In a study of healthy individuals, topical application of rapamycin significantly reduced the expression of p16INK4A, a marker of cellular senescence, in the epidermal layer of the skin.
Other skin aging markers, such as p21Cip2 and TP53, also showed trends toward reduction, although these changes did not reach statistical significance.
These findings indicate that rapamycin may have the ability to slow or even reverse certain aspects of skin aging, potentially improving the overall health and appearance of the skin [1].
While the available evidence suggests that rapamycin and its derivatives can positively affect the immune, cardiovascular, and integumentary systems, the overall number of studies still needs to be bigger.
Additionally, the effects of these drugs on other physiological systems, such as the respiratory, digestive, renal, and reproductive systems, have yet to be extensively explored.
Furthermore, the optimal dosage and long-term safety of rapamycin and its derivatives in humans remain to be fully studied.
Ongoing clinical trials are investigating these aspects, and the potential of rapamycin to improve various aging biomarkers, like walking speed, grip strength, and epigenetic markers.
As rapamycin research and its antiaging potential continue to evolve, it is clear that this drug holds promise as a geroprotector that can enhance longevity and health span.
However, more comprehensive and long-term studies are needed to understand its effects fully and determine the best clinical application strategies.
You can find more information about this study in The Lancet Healthy Longevity.
[1] https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext
