Evaluation of off-label rapamycin use to promote healthspan in 333 adults

Abstract

Rapamycin (sirolimus) is an FDA-approved drug with immune-modulating and growth-inhibitory properties. Preclinical studies have shown that rapamycin extends lifespan and healthspan metrics in yeast, invertebrates, and rodents. Several physicians are now prescribing rapamycin off-label as a preventative therapy to maintain healthspan. Thus far, however, there is limited data available on side effects or efficacy associated with use of rapamycin in this context. To begin to address this gap in knowledge, we collected data from 333 adults with a history of off-label use of rapamycin by survey. Similar data were also collected from 172 adults who had never used rapamycin. Here, we describe the general characteristics of a patient cohort using off-label rapamycin and present initial evidence that rapamycin can be used safely in adults of normal health status. Supplementary Information The online version contains supplementary material available at 10.1007/s11357-023-00818-1.

Quantification of healthspan in aging mice: Introducing FAMY and GRAIL

“…Here, we find that frailty shortens the healthspan of mice by approximately 16-20% from the maximum possible healthspan given a fixed maximum lifespan. This percentage of time is similar to the concept of the "lost decade" in human health -the idea that people typically lose 10-20 years of high quality life due to disability and frailty (33). While the NIA Interventions Testing Program (ITP) as well as other groups have over the past two decades have identified many agents that extend lifespan, going forward tracking healthspan may allow the identification of agents that are just as effective (or more so) at adding healthy years to life.…”

The Long Scientific Journey of Sirolimus (Rapamycin): From the Soil of Easter Island (Rapa Nui) to Applied Research and Clinical Trials on β-Thalassemia and Other Hemoglobinopathies

“…Rapamycin was employed by different research groups using different dosages in different mouse strains with similar effects in increasing lifespan [ 68 ]. Starting from these pre-clinical studies concurrently demonstrating that mTOR is a key modulator of aging (but also of age-related diseases), Kaeberlein et al evaluated the potential of rapamycin use to promote health span in human adults [ 69 ]. They collected data from 333 adults with a history of off-label use of rapamycin and made a comparison with data collected from 172 adults who had never used rapamycin.…”

Intermittent rapamycin feeding recapitulates some effects of continuous treatment while maintaining lifespan extension

“…Given that we observed some sex-specific effects of the intermittent rapamycin treatment, it would be interesting in future studies to directly compare rapamycin wash out kinetics between male and female mice. In some cases, rapamycin is already prescribed off-label as a preventative therapy to maintain health span in humans, however, dosing and dosing interval varies widely with most people taking rapamycin once per week [ 53 ]. The plasma half-life of rapamycin differs between rodents and humans, with a reported mean terminal half-life of rapamycin in humans of 79 h [ 54 ].…”