Rapamycin extends murine lifespan but has limited effects on aging

TLDR

Aging is a major risk factor for many disorders, and targeting the aging process may offer broad therapeutic benefits, but it remains unclear whether rapamycin’s reported lifespan extension in mice reflects true slowing of aging or merely protection against specific age‑related pathologies. The study aimed to determine whether rapamycin slows the rate of aging in male C57BL/6J mice by evaluating a wide range of structural and functional aging phenotypes. Researchers performed a comprehensive, large‑scale assessment of numerous aging phenotypes in treated and control mice to test this hypothesis. Although rapamycin extended lifespan, it improved only a few aging traits, many of which were also affected in young animals, indicating that its longevity benefits are largely independent of genuine anti‑aging effects.

Abstract

Aging is a major risk factor for a large number of disorders and functional impairments. Therapeutic targeting of the aging process may therefore represent an innovative strategy in the quest for novel and broadly effective treatments against age-related diseases. The recent report of lifespan extension in mice treated with the FDA-approved mTOR inhibitor rapamycin represented the first demonstration of pharmacological extension of maximal lifespan in mammals. Longevity effects of rapamycin may, however, be due to rapamycin’s effects on specific life-limiting pathologies, such as cancers, and it remains unclear if this compound actually slows the rate of aging in mammals. Here, we present results from a comprehensive, large-scale assessment of a wide range of structural and functional aging phenotypes, which we performed to determine whether rapamycin slows the rate of aging in male C57BL/6J mice. While rapamycin did extend lifespan, it ameliorated few studied aging phenotypes. A subset of aging traits appeared to be rescued by rapamycin. Rapamycin, however, had similar effects on many of these traits in young animals, indicating that these effects were not due to a modulation of aging, but rather related to aging-independent drug effects. Therefore, our data largely dissociate rapamycin’s longevity effects from effects on aging itself.