Rapamycin Exhibits Similar Life-Extending Effect as Eating Less

Dietary restriction has long been one of the most robust, evidence-backed methods to extend lifespan across multiple species. But if the idea of prolonged fasting or reduced calorie intake sounds unappealing, science may now offer a promising alternative.

A new systematic review, published in Aging Cell, reveals that rapamycin – a compound originally developed as an immunosuppressant – can deliver comparable life-extending effects in eight different vertebrate species. This positions the drug as a potential alternative to traditional dietary restriction.

Exploring alternatives to caloric restriction

For decades, reducing caloric intake without causing malnutrition – known as dietary restriction (DR) – has been shown to extend lifespan in various organisms. However, its application in humans is often limited by poor adherence and potential health trade-offs.

Researchers have sought compounds that mimic the effects of dietary restriction without the need to reduce food intake. These agents, known as dietary restriction mimetics (DRMs), have gained significant interest in aging research.

Two leading DRMs are rapamycin and metformin. Rapamycin was first isolated from soil bacteria on Easter Island in 1975. It functions by inhibiting the mechanistic target of rapamycin (mTOR) pathway, a central regulator of cell growth and metabolism. Studies have shown that rapamycin extends lifespan and slows epigenetic aging in organisms ranging from yeast to mice.

Metformin, widely prescribed for type 2 diabetes, activates the AMP-activated protein kinase (AMPK) pathway, improving insulin sensitivity and reducing circulating glucose. While it has shown promising lifespan-extending effects in some species – including nematodes and monkeys – the results remain inconsistent.

To evaluate the efficacy of these interventions, researchers from the University of Glasgow and the University of East Anglia (UEA) conducted a systematic review and meta-analysis to compare the effects of dietary restriction, rapamycin and metformin on vertebrate lifespan.

“DR – through intermittent fasting or reduced calorie intake – has been the gold standard for living longer. But it’s difficult for most of us to maintain long-term,” said Dr. Zahida Sultanova, from UEA’s School of Biological Sciences. “We wanted to know if popular anti-aging drugs like rapamycin or metformin could offer similar effects without the need to cut calories.”

A landmark meta-analysis across eight vertebrate species

The team analyzed data from 167 studies spanning 8 vertebrate species, including mice, rats, fish and primates, making this the largest meta-analysis of its kind. They compared three established longevity-promoting strategies: two types of DR (intermittent fasting and caloric reduction) and two DRMs (metformin and rapamycin).

They also assessed whether biological sex influenced outcomes and whether the mode of dietary restriction impacted its effects.

Both forms of dietary restriction reliably extended lifespan across all species analyzed, with no significant sex-specific differences. Interestingly, rapamycin also demonstrated a consistent lifespan-extending effect, almost on par with dietary restriction itself. In contrast, metformin did not produce consistent results.

“Our findings show that drug repurposing is a promising approach to improving people’s health and lifespan,” said Sultanova.

The future of lifespan extension

As researchers continue searching for practical, science-backed strategies to extend healthspan and longevity, rapamycin has emerged as a leading candidate – potentially offering the benefits of dietary restriction without the challenge of long-term caloric reduction.

“These findings don’t suggest we should all start taking rapamycin,” cautioned Dr. Edward Ivimey-Cook from the University of Glasgow. “But they do strengthen the case for its further study in aging research and raise important questions about how we approach longevity therapeutics.”

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While rapamycin is already approved for clinical use in other contexts and is undergoing trials for ageing-related outcomes, safety concerns remain. As an immunosuppressant, it may impair immune function, although recent studies indicate that low doses can be safely administered in healthy individuals.

Another key question is why different strains of the same species exhibit variable responses to DR or DRMs, with some benefiting and others experiencing adverse effects. Understanding this genetic variability is crucial for translating findings into human populations.

“There is a need for additional studies to explore the generalizability and applicability of these dietary restriction mimetics across other vertebrate species, particularly in humans,” the authors concluded.

Further research into the mechanisms, safety and scope of DRMs like rapamycin may unlock new tools to enhance healthy aging – without the hunger.

Reference: Ivimey-Cook ER, Sultanova Z, Maklakov AA. Rapamycin, not metformin, mirrors dietary restriction-driven lifespan extension in vertebrates: A meta-analysis. Aging Cell. 2025;n/a(n/a):e70131. doi: 10.1111/acel.70131

This article is a rework of a press release issued by the University of East Anglia. Material has been edited for length and content.