For centuries, humanity has sought the secret to a longer life, from the mythical philosopher’s stone to modern scientific research. A longstanding belief from studies on laboratory animals shows that caloric restriction can lead to increased lifespan. However, new insights suggest that certain compounds could offer a way to extend life while still enjoying a fulfilling diet.
Recent research led by a team of scientists has identified rapamycin and metformin as promising agents that mimic the effects of dietary restrictions. In a significant study, the team discovered that rapamycin may prolong lifespan nearly as effectively as caloric restriction itself, while metformin did not exhibit similar benefits.
The phenomenon of caloric restriction as a pathway to longevity gained attention nearly 100 years ago when studies showed that laboratory rats on a reduced-calorie diet outlived their well-fed counterparts. Notably, caloric restriction has remained the gold standard in longevity research.
While the benefits of consuming fewer calories are well established, adhering to a strict diet can be challenging and often unenjoyable for many individuals. This prompted researchers to explore whether pharmaceuticals could provide similar advantages without the burdens of dieting.
Rapamycin, discovered in the 1970s from soil bacteria in Easter Island, is currently utilized as an immunosuppressant to prevent organ transplant rejection. It functions by inhibiting a molecular switch that indicates nutrient availability to cells. Conversely, metformin is a synthetic derivative of a compound from the French lilac, predominantly used to manage blood sugar levels in patients with type 2 diabetes.
To understand the impact of these compounds on lifespan, the research team evaluated thousands of studies, ultimately focusing on 167 that detailed findings across eight vertebrate species, including fish and monkeys.
After thorough analysis, it was determined that caloric restriction consistently outperformed both rapamycin and metformin in promoting longevity. However, rapamycin demonstrated compelling potential as a leading candidate for new anti-aging therapies, while metformin showed no significant results.
Notably, both dietary restriction and rapamycin offered similar longevity benefits for both males and females, regardless of whether the approach involved portion control or intermittent fasting. This positions rapamycin as a central focus for further research into life-extending therapies that may mitigate age-related health issues, from cancer to dementia.
Promising Findings with Caution
While the results are promising, researchers caution against premature conclusions. They identified significant variability in results across different studies, with some showing that both caloric restriction and rapamycin could even shorten lifespan. Additionally, much of the data stems from studies on mice and rats, organisms which share genetic similarities with humans but are not identical.
Moreover, rapamycin could induce unwanted side effects, including repression of immune function. To address this, researchers are exploring lower doses of the compound that might deliver its benefits without adverse effects.
Preliminary human trials using intermittent, low doses of rapamycin show positive health indicators, while trials for metformin are underway with results expected in the coming years.
As of now, health experts advise against self-medicating with rapamycin. Nevertheless, the research underscores the importance of targeting a specific molecular pathway to replicate the effects of caloric restriction. The goal remains to develop therapies that promote longevity while preserving a healthy lifestyle and enjoyment of life’s pleasures, such as a slice of chocolate cake.
Zahida Sultanova, Post Doctoral Research Fellow, School of Biological Sciences, University of East Anglia
