5/30/24

Answering Your Questions on Longevity | 37 - Ask Matt Anything #4

We've hit 6,000 subscribers!

To celebrate this milestone and to thank you for your support, we've created an Ask Matt Anything (AMA) episode out of questions that you left on our previous podcast episodes. You guys ask great questions—we really enjoy thinking about the points you raise and gaining a more comprehensive and nuanced understanding of a given topic ourselves.

So here it is: an AMA buffet of longevity-related topics, from the effects of metformin and calorie restriction to methods for self-experimentation to what is special about long-lived species and much more.

We'll be releasing another special episode when we get to 10,000 subscribers, so stay tuned (and get your friends to subscribe).

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!

Taurine deficiency as a driver of aging

Matt and colleagues coauthored this paper demonstrating a decline in circulating taurine with age in mice, monkeys, and humans, as well as the ability to stem the decline via taurine supplementation. Taurine supplementation had positive effects on lifespan in worms and mice and on healthspan in monkeys, possibly by addressing several hallmarks of aging such as cellular senescence, DNA damage, inflammation, and more. Yeast did not experience any lifespan benefits from taurine supplementation. The researchers also found a correlation between lower taurine levels and several age-related pathologies in humans.

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

Matt discusses this paper in a different podcast episode. Researchers tested the effects of seven drugs, including alpha-ketoglutarate, on mice. 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. Alpha-ketoglutarate and the other drugs produced no lifespan effects on mice.

Big mice die young: early life body weight predicts longevity in genetically heterogeneous mice

This study found that mice with a smaller body size outlived those with a larger body size. This association was present in both male and female mice and was stronger for weights taken earlier rather than later in life, suggesting that low body weight at earlier ages is particularly advantageous for mouse longevity. The authors hypothesize that body weight is likely a surrogate measure of biological changes that influence weight as well as later life outcomes.

Rapamycin news

Many of our podcast listeners are interested in questions about rapamycin dosing, how to get a prescription for rapamycin, and how rapamycin might interact with other supplements or drugs. This website is a great resource for getting more clarity on some of these questions, as well as for hearing about others' experiences with rapamycin and other longevity medications.

Reversal of biological age in multiple rat organs by young porcine plasma fraction

This paper details the experiment featured in a previous podcast episode on Harold Katcher's assertion that injecting young pig blood into rats made rats biologically younger. Scientists examined the effect of a plasma fraction from young adult pigs on epigenetic clocks for rat tissues, and found that the treatment reduced epigenetic age, as measured by the clocks, by up to 30 percent across several rat organs. E5 also improved other parameters such as inflammatory markers and grip strength. The paper did not present lifespan data for the treated rats.

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Answering Your Questions on Rapamycin: Optimal doses, tests, & stacks | 20 - AMA #3