Rapamycin fed late in life extends lifespan in genetically heterogeneous mice: interpreting results from our Intervention Testing Program (ITP) study
When reading our Nature paper and the News and Views commentary, here is some information that will put the experimental results in perspective and also underscore the significance of the Intervention Test Program (ITP) in general:
Details about the study and the Intervention Testing Program (ITP):
a. The study was conducted by three equal co-PIs, at three institutions:
- Dr. David E. Harrison, The Jackson Laboratory
- Dr. Richard A. Miller, University of Michigan
- Dr. Randy Strong, University of Texas Science Health Science Center at San Antonio
| Links to information related to the study | ||
|---|---|---|
| The Nature paper | Nature News and Views commentary | |
b. Dr. Nancy Nadon, of the National Institute of Aging (NIA), represents the NIA in the program; two committees advise the PIs.
c. The ITP is ongoing. Experts are invited to suggest treatments via the ITP website, which also includes a list of all compounds tested to date.
Why the rapamycin study is important and unique:
a. The mice whose lives were extended were highly heterogeneous progeny from a 4-strain cross, so it is unlikely that the life extension emerged merely from postponing a few diseases.
b. The rapamycin treatment did not start until the mice were fairly old—about 600 days of age, roughly equivalent to about 60 years for human beings.
c. The treatment is targeted to a single enzyme, so it is well defined on a biochemical level.
No other intervention
has been this effective…
on such a diverse population…
when started so late in life.
The size of the rapamycin effect and what a treatment this effective would mean for humans:
| Lifespan increase in mice, expressed as… | Males | Females |
|---|---|---|
| Lifespan increase in age at 90% mortality (a mortality statistic thought to best express effects of aging rather than vulnerability to specific disease because it measures maximal lifespan): | 9% | 14% |
| Lifespan increase from 600 days of age | 28% | 38% |
These results would be equivalent to increasing the life expectancy of a 60-year-old human being by 10 years. This impressive increase suggests that rapamycin may be acting on some fundamental mechanism of aging.
As mammals age, an increasing number of disease processes develops in each individual, which results in an exponential increase in mortality risk. For example, an older person who dies from cancer could have progressive atherosclerosis and diabetes as well. Even if the cancer was cured, this individual would live just a few more years—in a progressively deteriorating state—until he or she died from a failure of the circulatory system or diabetes. Thus, our results—a large lifespan increase in a genetically diverse population—imply that rapamycin operates by reducing the risk of death from multiple causes of mortality, i.e., by delaying aging, rather than by curing a disease.
This illustrates the importance of research on mechanisms of aging using strategies employed by the ITP: Success in retarding aging extends healthy lifespan far, far more effectively than does success in preventing any one specific disease.