The recent reports of lifespan extension in mice treated with the FDA-approved mammalian TOR (mTOR) inhibitor rapamycin confirms the previous demonstration of pharmacological extension of maximal lifespan in mammals. But extension of lifespan does not necessarily indicate effects on aging; lifespan extension could be caused by isolated suppression of specific life-limiting pathologies, such as cancers. This is a plausible scenario, because rapamycin has known antineoplastic properties, and tumors are the leading cause of death in many mouse strains. This includesC57BL/6J and other strains in which rapamycin was shown to have longevity effects. An alternative scenario is that rapamycin’s antineoplastic effects represent one aspect of a more general effect of this compound on aging.
To test if mTOR inhibition by rapamycin has decelerating effects on mammalian aging rates three healthy male C57BL/6J cohorts of different ages were treated with rapamycin and compared to control animals. The comprehensive large-scale phenotypic analysis was performed in the German Mouse Clinic (GMC).
Mice were treated with rapamycin for one year. For the youngest group treatment started with 4 months (age at analysis: 16 months), for the middle-aged group with 13 months (age at analysis: 25 months) and for the oldest group treatment started with 20-22 months.
The testing of more than 150 age related parameters revealed several tests where rapamycin shows clear effects. For example it is known that exploratory behaviour as well as learning and memory usually decrease with aging. In rapamycin treated mice these parameters were ameliorated. Similar observations were made for metabolic analyses, immune parameters, red blood cell counts and others. However, in most of the cases not only the middle aged or old group showed improvements but also the young animals. This indicates that the effects of rapamycin in the aging mouse cohorts were not due to a retardation of aging but were related to aging-independent effects of the drug. The scientists conclude that the extension of life span in rapamycin treated animals is due to the effect of the drug to inhibit development of tumors. This effect was also shown during the analysis in the GMC: The drug suppressed carcinogenesis in aging mice.
Neff, et al., Rapamycin extends murine lifespan but has limited effects on aging, J Clin Invest. 2013;123(8):3272–3291. doi:10.1172/JCI67674.