Transient Rapamycin Treatment Extends Mice Life Span By 60%

 A brief stint of rapamycin treatment in late middle age dramatically extends life span in mice by 60%; the biggest extension achieved with pharmaceuticals so far

We already know that two primary repurposed pharmaceuticals ,rapamycin and metformin, have life extension potential from previous animal data. Rapamycin has shown the greatest effect so far, and is currently being tested in a trial on dogs to test its possible rejuvenative effects. Interestingly, while rapamycin has detrimental side effects in long term treatment, short term application has emerged as an alternative; an alternative that may even have more potent results in extending life and reducing inflammation. 

What did the latest study involve?

The structure of rapamycin, also known as Sirolimus

Researchers at the University of Washington conducted a study to find out the optimal dosage regimen of rapamycin in mice. They treated one group of mice at 20 months of age, which translates to around 60 years of age, with rapamycin for 90 days and then ceased treatment - monitoring life span following the intervention. 

A sizeable boost

Rapamycin inhibits the mTOR pathway, impacting on growth and increasing cellular recycling. Credit: David Guertin

To their surprise, mice receiving rapamycin experienced life extension of up to 60% in comparison to the control group. If correct, this is the largest extension yet achieved with a pharmaceutical approach. The longest lived mouse in the study (affectionately named Ike) lived for a grand old age of 1400 days, which is the equivalent of about 140 years for a human. 

"It's quite striking that short-term rapamycin treatment had such a lasting impact on health and survival after the treatment was stopped. To our amazement, considering the relatively small size of the group of mice we studied, Ike might have been one of the longest lived mice of his kind"

A complicated picture

While this data is mostly extremely positive, male mice outlived females at higher doses, and high doses appear to make female mice more susceptible to certain kinds of cancers. Middle aged female mice receiving high doses were less likely to develop other types however, which complicates the findings somewhat. 

The burst of treatment also had a curious side effect of altering the microbiome of the mice, increasing the amount of segmented, filamentous bacteria - a type rarely seen in older mice. It wasn't definitively clear whether this was a beneficial effect however. 

Segmented filamentous bacteria. Credit: Ivaylo Ivanov and Dan Littman (NYU Langone Medical Center) and Doug Wei (Carl Zeiss SMT, Inc.)

"The microbiota changes are an intriguing finding, and will be an exciting area of future aging interventional research. We were pleased to see that the initiation of rapamycin treatment at middle age, rather than the full lifespan of the mice, had an effect"

 

Moving to humans

While we await data from the canine trial, rapamycin continues to be a valuable potential longevity treatment but remains tricky in comparison to other drugs. Its side effects and possible gender differences in response to the drug are factors to consider as we move forward. Developing similar compounds that inhibit mTOR but have less of the detrimental side effects is one alternative when it comes to human use, but if dosages can be honed in humans, rapamycin may remain one of the most promising life extension treatments to date. 

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