Besides targeting older animals, the study is also unusual for its use of a genetically diverse population of mice. Most aging studies use inbred strains, which are easier to work with in the laboratory. Harrison says that a genetically heterogeneous study population rules out the possibility of accidentally treating a specific disease that happens to be prevalent in the inbred strain being used. Much like humans, the mice used in the study have a wide variety of susceptibility to the various diseases of aging. Since the life-span-extending effects were seen throughout the study population, says Harrison, rapamycin must be altering some fundamental aging mechanism that drives a broad range of age-related defects.
“People who study the biology of aging feel that in order to deal with diseases of aging, it’s much more efficient to target underlying mechanisms, rather than focusing on heart disease or cancer or diabetes or Alzheimer’s or Parkinson’s separately,” says Harrison. “If we could alter underlying mechanisms of aging, all of these things would be postponed.”
Exactly what rapamycin’s mechanism might be remains to be seen, says Harrison. The drug inhibits a protein called target of rapamycin (TOR). Normally, TOR helps cells manufacture new proteins, and hinders the destruction of malfunctioning ones. While these processes are known to be involved in aging in fruit flies, nematode worms, and yeast, TOR’s precise role in life-span regulation is still unclear.
It’s promising to learn that TOR also participates in mouse aging, because it means that the mechanism is relevant in all four model organisms most widely used to study the aging process, says Matt Kaeberlein, a professor of pathology at the University of Washington and coauthor of a commentary accompanying the new study. “The fact that it’s been conserved over that large evolutionary distance makes it an intriguing possibility that TOR signaling has similar effects in people,” he says.
Teasing out precisely how TOR signaling is linked to life span could reveal new targets for potential anti-aging drugs. By zeroing in on a different part of the TOR pathway, future drugs may be able to avoid some of rapamycin’s troubling side effects.
The authors caution that it’s still not clear whether rapamycin will have similar life-span-enhancing effects in humans, and that because of its known toxicities, such as fungal infections and pneumonia, the drug should not be taken by the general population as a kind of universal fountain of youth.
A more realistic goal, says Kaeberlein, is to investigate whether it can treat specific age-related disorders–as in the several ongoing cancer trials, for example. Studies have also suggested that interfering with the TOR signaling pathway could slow the progression of Huntington’s disease, Alzheimer’s disease, and diabetes. “Realistically,” says Kaeberlein, “I think what most of us are hoping for, and are somewhat optimistic about, is the idea that you may be able to get an extra decade–possibly an extra two decades–of relatively good health.”