Rapamycin May Boost Lifespan More Significantly with Reduced Caloric Intake

The drug rapamycin shows effects on life extension that are nearly comparable to calorie restriction, based on the largest study exploring the lifespan of various vertebrate species.

Researchers are probing if lifestyle changes like diet and exercise can enhance longevity while mitigating aging-related health issues. For instance, calorie restriction, when balanced with nutritional needs, has demonstrated extensions of lifespan in non-human animals of up to 40%.

“In our field, we have long recognized that calorie restriction often yields positive results,” says Matt Kaeberlein, who was not involved in the recent research from Washington University in Seattle.

Another area of interest lies with potential anti-aging medications, such as rapamycin, initially developed as an immunosuppressant. The combination of rapamycin with the cancer treatment trametinib has shown a 30% increase in mouse lifespan earlier this year.

Currently, Zahida Sultanova from the University of East Anglia, along with her collaborators, is reviewing data from 167 studies on lifespan interventions across eight vertebrate species, such as fish, mice, rats, and rhesus monkeys, though not in humans.

The findings indicated that dietary restrictions, regardless of whether they primarily involve calorie reduction or intermittent fasting, extend the lifespan of all eight species, regardless of sex. Rapamycin appears to produce effects similar to these. They also examined the type 2 diabetes medication metformin, which has been suggested as a potential longevity stimulant, but found no benefits regarding lifespan.

However, Sultanova advises against individuals self-prescribing rapamycin based on these findings. “High doses of rapamycin can have side effects, as it is designed to suppress the immune system,” she states, noting that studies in mice have indicated it might affect reproduction. Nonetheless, early data from a recent trial suggest low-dose rapamycin is relatively safe for healthy elderly individuals.

Kaeberlein also warns against using medication or limiting calories solely to combat aging, as this could be linked to physical debilitation and mental health issues. “We must better understand the ratio of risks to rewards in humans before making such decisions,” he states. “Rapamycin might be beneficial for certain individuals, and ongoing research aims to clarify who those individuals are.”

Other medications similar to rapamycin, termed Rapalogs, might offer even more promising options with fewer adverse effects for lifespan extension, claims Sultanova.

Kaeberlein adds that while these results align with existing literature, “the effect sizes observed in shorter lifespans typically surpass those in longer ones, so caution is warranted when comparing across species.”