Low Dose Continuous Rapamycin Favorably Alters the Aging Immune System
Rapamycin is an immunosuppressant long used in transplant medicine at relatively high doses. At lower doses, it slows aging and extends life in animal studies by mimicking some of the beneficial metabolic reactions to calorie restriction, such as increased autophagy. A fair number of people use rapamycin with the hopes of achieving the same outcome, though the human data for this use case and dosage remains sparse. Normally rapamyin is taken once a week, but here researchers mix it in with the diet in a study of immune aging in mice.
Aging is the gradual accumulation of structural and functional changes in an organism over time, including immune remodeling and a progressive increase in basal inflammation, or inflammaging. The mTOR pathway is a central driver of aging-related diseases, such as cancer, chronic inflammation, and neurodegeneration; pharmacological inhibition with rapamycin is associated with reduced aged-related morbidity and increased lifespan across species. Nonetheless, concerns remain about the use of rapamycin, a well-established immunosuppressant in transplant medicine, as an anti-aging intervention.
Here, we evaluated the impact of prolonged low-dose dietary rapamycin on the aging immune system. Treatment did not significantly alter innate or adaptive immune cell populations, including brain resident microglia; however, it attenuated the age-associated accumulation of IL-17-producing γδ T cells, particularly in the peritoneal cavity. After a peripheral inflammatory endotoxin challenge, circulating IL-17 levels were significantly reduced and correlated with an attenuation of microglia inflammatory phenotype. These findings suggest that prolonged low-dose rapamycin exposure exerts minor systemic immune changes, while selectively limiting age-related γδ T cell expansion and neuroinflammation associated with systemic inflammation.