US scientists have discovered that rapamycin, first discovered in a soil sample from Easter Island, can significantly extend life expectancy in genetically heterogeneous populations of mice. Rapamycin, which is used primarily to prevent rejection following kidney transplants, is an immunosuppressant that interferes with TOR (target of rapamycin) signalling. Inhibition of TOR signalling was already known to extend lifespan in invertebrates but a similar effect in mammals had not been directly demonstrated, although calorie restriction – which has been shown to enhance life expectancy in mammals – is believed to interfere with TOR signalling. The original aim of the present study was to begin treating the mice at 4 months of age but problems in developing a suitable formulation of rapamycin meant that treatment was delayed until they were 20 months old, the equivalent of 60 years old in human terms. Although the team were doubtful that the study would still provide a clear-cut result they went ahead with dosing anyway and found that, compared with untreated animals, the maximal lifespan (age at which 10% survive) was increased by 14% for female mice and by 9% for male mice. In terms of life expectancy, this is equivalent to a 38% increase for the females and a 28% increase for the males. The disease patterns and causes of death in treated and untreated mice were found to be similar. In a separate study, rapamycin was also found to increase survival in both male and female mice when administered from the age of 9 months.
If similar effects on longevity were seen in humans, inhibition of mTOR signalling, even from age 60, could still significantly enhance lifespan, although an increased susceptibility to infections and possible risk of developing lymphoma or other malignancies as a result of immunosuppression would need to be considered.
The study is published in the journal Nature.