We read every single comment on our social media and Youtube channels and enjoy hearing your feedback, questions, and comments on our podcast.

Our recent episode on the Interventions Testing Program's recent tests on various longevity interventions sparked some interesting debate on X. City of Hope National Medical Center's Alfred E. Mann Family Foundation Chair in Diabetes and Cancer Metabolism Charles Brenner made a remark about the potential negative effects of rapamycin on humans, while Ponce De Leon Health Chief Operating Officer Mike Muldoon plugged the calcium alpha-ketoglutarate supplement Rejuvant (the ITP tests reported no lifespan extension of alpha-ketoglutarate on mice). Matt responded to these comments on X and some interesting back and forth with Charles and Mike ensued.

In this episode, Matt and Nick take a magnifying glass to Charles' and Mike's feedback and examine the published data—and some unpublished data—to consider and respond to their claims. They also discuss the allure of phrases such as "scientifically proven" and "clinically proven" in marketing, and the importance of approaching such phrases with a critical mindset and an eye towards study robustness and methodology as well as the researchers' impartiality.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin

In this podcast episode, Matt discusses this paper in which researchers tested the effects of seven drugs—alpha-ketoglutarate, 2,4-dinitrophenol, hydralazine, nebivolol, 16α-hydroxyestriol, sodium thiosulfate, and canagliflozin—on mouse longevity. 16α-hydroxyestriol significantly increased male mouse lifespan, but decreased female mouse lifespan. Canagliflozin also increased male mouse lifespan and decreased female mouse lifespan when mice received it in later life. The other drugs—including alpha-ketoglutarate, which the supplement Mike Muldoon references in his post contains—produced no lifespan effects on mice.

Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice

This study laid some of the groundwork for the investigation of alpha-ketoglutarate in the Interventions Testing Program. Researchers found that alpha-ketoglutarate reduced chronic inflammation and extended health- and lifespan in mice without inducing any significant adverse effects. Matt has said on several occasions that he did not find the lifespan data in this study particularly convincing as the effect size was small, but did find the frailty and healthspan data intriguing.

Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test

Rejuvant is a sustained release alpha-ketoglutarate supplement that describes itself as "the first patented, science-backed longevity supplement that reduces biological age and gives you the focused energy you need today". This study reports an eight-year decrease in biological aging as measured by DNA methylation clocks after an average of seven months of Rejuvant supplementation. One of the study's coauthors is a Rejuvant scientific consultant.

Rejuvant website

Take a look at this website to see some of the claims made by Ponce de Leon Health about Rejuvant.

Sirolimus for treatment of patients with inclusion body myositis: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2b trial

This study tested the efficacy of rapamycin in treating the rare inflammatory muscle disorder inclusion body myositis, a common disorder in patients over the age of 50, and found no evidence that rapamycin was an effective drug for tackling the disease. The study did not observe any statistically significant changes in patient muscle function. The most commonly-reported side effect in this study was mouth sores, which have also been observed with rapamycin use in other studies.