Rapamycin in aging and disease: maximizing efficacy while minimizing side effects.

Simon C Johnson,Matt Kaeberlein

doi:10.18632/oncotarget.10381

Simon C Johnson, Matt Kaeberlein

Open Access

https://doi.org/10.18632/oncotarget.10381

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Abstract

Experimental geroscience has identified rapamycin as a top candidate for promoting healthy aging and longevity in mammals. As multiple independent studies have successfully reproduced the lifespan and healthspan promoting effects of rapamycin, the focus has shifted to possible translational use. While a promising compound, clinical use of rapamycin is limited by concerns of side effects associated with the drug. Studies aimed at defining optimal dosage regimen, delivery route, and formulation will allow for benefits to be maximized while reducing side effects.

Highlights

Rapamycin is a leading candidate compound for promoting healthy longevity by targeting aging
Doses used to extend lifespan in mice are generally free from these side effects; lifespan-prolonging doses of www.impactjournals.com/oncotarget rapamycin may result in a different set of adverse effects in mice, including altered glucose homeostasis, gonadal atrophy, and increased incidence of cataracts [5]
One published study has provided even a partial dose response, finding that when treatment was initiated at 9 months of age, 42 ppm encapsulated form of rapamycin (eRAPA) resulted in a greater magnitude of lifespan extension compared to 14 ppm, while 4.6 ppm resulted in a smaller effect [6]

Summary

Introduction

Rapamycin is a leading candidate compound for promoting healthy longevity by targeting aging. One published study has provided even a partial dose response, finding that when treatment was initiated at 9 months of age, 42 ppm eRAPA resulted in a greater magnitude of lifespan extension compared to 14 ppm, while 4.6 ppm resulted in a smaller effect [6].

Results

Conclusion