A large meta-analysis has found that the drug leading the charge in anti-aging science is just as effective in protecting cells and cognitive function as cutting calories or intermittent fasting (IF). It's the most comprehensive study of rapamycin yet.
In the largest study of its kind, researchers from the University of East Anglia (UEA) and the University of Glasgow looked at 167 studies conducted on lifespan-extending therapies on eight different vertebrates – including primates, rodents and fish – to see how rapamycin compared to traditional methods of healthy aging like cutting calories or fasting.
"Dietary restriction – for example through intermittent fasting or reduced calorie intake – has been the gold standard for living longer," said co-lead researcher Dr Zahida Sultanova, from UEA’s School of Biological Sciences. "But it’s difficult for most of us to maintain long-term.
“We wanted to know if popular anti-aging drugs like rapamycin or metformin could offer similar effects without the need to cut calories.”
Rapamycin is not new – it was identified in 1972, in soil samples taken from Rapa Nui, or Easter Island, as European explorers coined it, in 1964. But it would be decades before scientists unlocked its multifaceted promise. Isolated from the Streptomyces hygroscopicus bacterium, rapamycin rose to prominence as an anti-fungal and anti-cancer drug and an immunosuppressant. Several decades later, it became the target compound in geroscience – now a burgeoning field studying the biological mechanisms of aging and age-related diseases.
It's now the subject of numerous studies, including testing it for the potential treatment of chronic fatigue syndrome.
Without getting too deep in the science, rapamycin (also known as sirolimus) is an mTOR (mechanistic Target Of Rapamycin) inhibitor, which regulates crucial biological functions like cell growth and repair. Rapamycin essentially signals to mTOR to send out the message to slow down and do some clean-up (autophagy). This makes cells better at responding to stress and presses pause on unchecked cell growth, which can lead to the build-up of damaged material – and trigger diseases like cancers and dementia.
While it doesn't reverse aging, it delays the biological aging process to promote healthy aging. It's gained US Food and Drug Administration (FDA) approval in other areas, including to prevent transplanted organ rejection and to treat rare lung disease lymphangioleiomyomatosis (LAM) and some rare cancers.
In this latest study, the data showed that rapamycin extended lifespan across the eight vertebrate groups on par with eating less and/or fasting. Meanwhile, another drug that's been targeted for its potential healthy aging properties, metformin, wasn't as effective. Metformin has shown early promise, particularly in people with type 2 diabetes, potentially lowering the risk of cancer and cognitive decline. It's also the focus of a current study known as The Targeting Aging with Metformin (TAME) trial, a US-wide six-year clinical trial with more than 3,000 people aged 65-79 taking part. However, that's ongoing (but certainly one to watch).
The UEA scientists found that "dietary restriction" – either through cutting calories or intermittent fasting – extended the lifespans of all eight vertebrates in the 167 studies. However, rapamycin was also consistent in doing this, while metformin wasn't. What's more, rapamycin's healthy aging biomarkers were consistent across males and females.
“These findings don’t suggest we should all start taking rapamycin," said co-lead researcher 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.”
While there's no silver bullet for stopping the aging process, the researchers highlighted that current interventions can prove challenging for many – long-term calorie-restricted diets and intermittent-fasting regimens can be challenging to maintain. If medical treatment could achieve the same healthy-aging results, regardless of diet, rapamycin's appeal is pretty clear.
“Our findings show that drug re-purposing is a promising approach to improving people’s health and lifespan," added Sultanova.
While the researchers' findings are based on studies on non-human vertebrates, rapamycin is currently under investigation in human trials, which will assess the drug for safety as well as efficacy.
The study was published in the journal Aging Cell.
Source: University of East Anglia