Matt and Nick discuss a recent New York Times article about rapamycin and its potential as a life-extending and/or anti-aging drug (the article quotes Matt). Matt answers various questions from Nick related to the article about topics including whether one should "feel something" when taking rapamycin, precautions to take when using the drug off-label, and what we know about rapamycin and fertility, cholesterol levels, and neurodegenerative disease. Matt also discusses likely reasons behind the mixed results observed thus far in human clinical trials of rapamycin, and emphasizes the need for well-powered, randomized clinical trials to better profile and understand the true efficacy of rapamycin in humans.

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!

Anti-Aging Enthusiasts Are Taking a Pill to Extend Their Lives. Will It Work?

This New York Times article, which quotes Matt, sparked the discussion in this Longevity This Week episode. The article introduces rapamycin as a drug-of-interest to the longevity community as well as an immunosuppressant for organ transplant patients. It then discusses studies exploring potential benefits of rapamycin supplementation in humans, some of the complexities of conducting such research, and potential risks and side effects of taking rapamycin.

Safety and efficacy of rapamycin on healthspan metrics after one year: PEARL Trial Results

This preprint describes the results of the 12-month double-blinded, randomized, placebo-controlled PEARL trial Matt discusses in this episode. 114 individuals between the ages of 50 and 85 received 5 mg or 10 mg of compounded rapamycin per week, or a placebo. The preprint reports that rapamycin is safe and well-tolerated as well as some intriguing potential benefits of rapamycin, though more work is necessary to more definitively determine rapamycin's effects, if any, on human healthspan.

Case report: Severe asymptomatic hypertriglyceridemia associated with long-term low-dose rapamycin administration in a healthy middle-aged Labrador retriever

In this episode, Matt mentions one dog that developed high triglycerides after receiving rapamycin in a clinical trial. This paper, which Matt coauthored, details that case study: an eight-year-old Labrador retriever developed severe hypertriglyceridemia after six months of rapamycin treatment. While the causal relationship between rapamycin administration and the elevated triglycerides is not conclusive, a causal connection between the two seems likely given that the hypertriglyceridemia resolved 15 days after the dog went off rapamycin.

Sirolimus-induced hyperlipidaemia in liver transplant recipients is not dose-dependent

This study is one of several suggesting that the rapamycin administration causes lipid abnormalities in transplant patients. Six liver transplant recipients experienced hypertriglyceridaemia and moderate total cholesterol increases after receiving rapamycin.

Sirolimus Changes Lipid Concentrations and Lipoprotein Metabolism in Kidney Transplant Recipients

Six kidney transplant recipients in this study experienced increased total plasma cholesterol and triglyceride levels during rapamycin administration. These increases were reversible. The researchers suggest that higher adipose tissue lipase activity or lower lipoprotein lipase activity may be responsible for the lipid changes that accompany rapamycin dosing.