Autophagy takes it all – autophagy inducers target immune aging

I don’t think this has been posted here before, but pretty interesting:

Autophagy, as the key nutrient recycling pathway, enables eukaryotic cells to adapt to surging cellular stress during aging and, thereby, delays age-associated deterioration. Autophagic flux declines with age and, in turn, decreases in autophagy contribute to the aging process itself and promote senescence. Here, we outline how autophagy regulates immune aging and discuss autophagy-inducing interventions that target senescent immune cells, which are major drivers of systemic aging. We examine how cutting-edge technologies, such as single-cell omics methods hold the promise to capture the complexity of molecular and cellular phenotypes associated with aging, driving the development of suitable putative biomarkers and clinical bioassays. Finally, we debate the urgency to initiate large-scale human clinical trials. We give special preference to small molecule probes and to dietary interventions that can extend healthy lifespan and are affordable for most of the world’s population.

Autophagy takes it all – autophagy inducers target immune aging

Includes a section on “Autophagy induction by rapamycin” among other related topics

Ground-breaking results from a phase II clinical trial with 264 human participants revealed a significant effect of RAD001 (Everolimus, a “rapalog”) administration on vaccine efficacy (Mannick et al., 2018). Participants in the study who had received a daily low dose of RAD001 (100 or 500 μg) for 6 weeks exhibited a significantly stronger response to flu vaccine and had fewer infections in the following year (Mannick et al., 2018). Whether the effect is modulated via autophagy is unknown.

In addition, a recent drug screen using human primary fibroblasts identified rapamycin as a potent inhibitor of SASP (Herranz et al., 2015). As previously discussed, SASP and senescence in immune cells as well as in HSCs, contribute to age-associated pathologies (Chen et al., 2009; Desdín-Micó et al., 2020). Therefore, preventing immune senescence in older people with rapamycin or other rapalogs appears to be a promising approach in the development of geroprotective treatments for diseases that disproportionally affect the elderly, such as seasonal flu, COVID-19 and osteoarthritis (Bischof et al., 2021; Dhanabalan et al., 2021 preprint).


Since autophagy is inhibited by NAC (by about 50%), I’d like to know when most of the autophagic effects occur after taking rapamycin? Is it within the first couple of days that most of the autophagy occurs, or is it a steady process throughout the week until the dosage decreases substantially?

NAC has a half-life of 6.25 hours, so a dose of 3.2 g should be cleared within a day.

I am considering skipping my NAC supplementation on the day of taking Rapamycin and the day after based on the information found in this paper: