Peter Attia MD171- Longevity science: caloric restriction studies, aging biomarkers & possible longevity molecules
At a glance
WHAT IT’S REALLY ABOUT
Steve Austad on Caloric Restriction, Lab Mice, Biomarkers and Longevity Drugs
- Austad describes an unusual path from math nerd and English major to New York cab driver, lion handler and, after studying aging in wild opossums, a longevity researcher.
- He argues that inbred, obese, sedentary lab mice and rats are a poor stand-in for humans, and that genetically heterogeneous mice like those in the ITP are better but still limited.
- Comparing the Wisconsin and NIA monkey studies, he and Attia conclude that diet composition, especially the roughly 28% sucrose in the Wisconsin diet, and baseline body weight likely drove the opposite outcomes.
- Human calorie-restriction trials achieved only modest restriction and mostly show benefits of moving overweight people to a healthy weight, while strict practitioners show downsides such as low bone density and muscle mass.
- Austad says better biomarkers are the limiting factor for human longevity research, and that rapamycin (by mouse data) and metformin (by human data) are the most promising molecules, perhaps in combination.
IDEAS WORTH REMEMBERING
5 ideasLab mice are a bizarre model for human aging
Austad says standard strains descend from fancy mice, were inbred for hundreds of generations and selected for fast growth and big litters. They are homozygous at every locus, much larger than wild mice and share nearly identical mitochondria, so he compares testing drugs in them to testing in the same set of twins.
Caloric restriction results depend on baseline weight and diet
The Wisconsin monkeys on a high-sucrose diet benefited from restriction, while the leaner, naturally fed NIA monkeys did not live longer. Attia concludes that the worse the diet, the bigger the benefit of restriction, and Austad agrees that nutrients count.
Constant calorie restriction is not practical or clearly desirable for humans
Participants in the human trials achieved only about 11 to 12% restriction instead of the 25% goal. The committed practitioners have low bone density, minimal sex hormones, little muscle and feel cold, and Austad calls it a non-starter for most people.
Short fasts may capture benefits of restriction
Austad notes lab rodents effectively fast most of each day, so timing may matter as much as total calories. Jay Mitchell's work showed that fasting mice for two or three days protected them from a lethal ischemic surgical injury, which changed Austad's thinking.
Wild mice suggest restriction may not help in nature
Austad's wild-derived mice showed no overall lifespan benefit from restriction, though the longest-lived ones were restricted and some restricted mice died early. He guesses restriction in the wild would shorten life because of longer foraging, slower wound healing and greater pathogen susceptibility.
WORDS WORTH SAVING
5 quotesWe have one comparison with humans now. It's mice. And just like you don't have much perspective when you close one eye, I don't think you have much perspective when you have one comparison, and, and that's kind of what we have now.
— Steve Austad
I never get excited by a single mouse study. Um, I get intrigued, but I don't get excited.
— Steve Austad
I think that even the best mouse is still a mouse. It's still one species, and it's a very different species than we are.
— Steve Austad
Nature was, nature was fine with us when we were living, you know, 35 years.
— Steve Austad
I think what we learned is the worse the diet, the more beneficial the caloric restriction. The better the diet, the less of an impact caloric restriction has.
— Peter Attia
High quality AI-generated summary created from speaker-labeled transcript.
