The idea of a drug capable of improving life expectancy is tantalizing for anyone involved in longevity-related research and the results of a recently released study seems to suggest that, in mice at least, rapamycin therapy is able to both make the animals live longer and improves markers of healthy aging. However the study’s results come with significant caveats, not the least of which is that the actual safety of the therapy is still uncertain.
In Brief: Rapamycin
Rapamycin is a drug used to treat people following an organ transplant and helps keep the body’s immune cells from rejecting the new tissue. Back in 2009, it was noticed that mice treated with rapamycin were living longer than their untreated counterparts. It wasn’t that these mice were just dying less often; they were actually living past their normal lifespan. Since this was the first time a drug had been seen to have such an effect in a mammal, the effect was both surprising and fascinating and has spawned new research into the exact mechanics behind the effect.
The study was looking at whether short-term doses of rapamycin could have long-term effects on longevity and healthspan—the length of time a person is healthy, not just alive. The mice were treated with 90 days of rapamycin once they reached 20 months of age, roughly the equivalent of a human 60 year-old. Compared to the controls, the treated mice lived up to 60% longer once the rapamycin treatment was stopped and on average had longer health spans. The longest-living mouse in the treatment group, “Ike”, even managed to live 1400. Since the mouse strain in use has an average male lifespan of around 700-800 days, this was quite the feat.
The findings also highlighted a need to better understand the dose-response relationship and imply gender differences in how the mice are affected. At lower rapamycin doses, both male and female mice showed improved longevity. At higher doses, the female mice became more vulnerable to aggressive cancers in the tissue used to produce blood, though they were also les likely to develop other types of cancers. Additionally, it was noted that the gut bacteria of the mice experienced certain shifts in population balance that the researchers weren’t sure could be considered a problem or not.
The main caveat to this study, aside from the fact that it was on animals, is that the researchers don’t actually know why rapamycin was causing these mice to live longer. One interpretation was floated that the treatment was rejuvenating the mice and making them biologically younger, but it doesn’t seem like any measurements needed to verify that idea were taken.
One past study that looked at rapamycin’s longevity effects found that, while a small number of aging traits, like memory impairments and low red blood cell counts, were improved in treated mice. This effect was also seen in young mice, which suggests something other than the aging process is being affected. It is also worth noting that the mouse strain used in both this past study and the one discussed above, called C57BL/6, has cancer as its leading cause of death. Since rapamycin is known to inhibit tumor formation, the prior study theorized that this was behind the increased longevity.
Rapamycin therapy was increasing the life expectancy of the treated mice and may also improve certain signs of healthy aging. However the reason why this happens, or even if it is a true anti-aging effect, is unknown. The finding that only a three-month course of the drug could produce long-term longevity improvements is a good contribution to the body of work surrounding rapamycin, but more needs to be done before humans worried about aging can start getting excited.
Gray, L., “Brief rapamycin therapy in middle-aged mice extends lives,” HS News Beat web site, last updated August 23, 2016; http://hsnewsbeat.uw.edu/story/brief-rapamycin-therapy-middle-aged-mice-extends-lives, last accessed August 24, 2016.
Bitto, A., et al., “Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice,” eLife, 2016; http://dx.doi.org/10.7554/eLife.16351.
“Inbred Strains of Mice: C57BL,” Mouse Genome Informatics web site, last updated April 9, 1998; http://www.informatics.jax.org/external/festing/mouse/docs/C57BL.shtml, last accessed August 24, 2016.