According to Peter Attia, mice engineered to overexpress the Klotho gene lived 15 to 20 percent longer.
“when they overexpressed that same gene that they had just knocked out and killed the mouse, the thing was living fifteen to 20% longer.”
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Peter Attia
3 episodes · 67 quoted claims
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Attia says the Klotho gene was found by accident when a Japanese researcher studying hypertension noticed a knockout mouse strain that died quickly from neurodegeneration.
“there was a a researcher in Japan who was really interested in understanding hypertension”
Peter Attia says he takes rapamycin for about two months and then stops for a month because it causes mouth ulcers.
“I'm probably on it for two months and then off it for a month.”
Peter Attia says caloric restriction and rapamycin are the only interventions that have extended life across yeast, worms, flies and mammals.
“It's very important to understand there are only two interventions full stop that have ever extended life across those four categories of eukaryotes. Caloric restriction and rapamycin.”
Peter Attia says the Matt Kaeberlein dog aging study testing rapamycin is expected to report results in 2026.
“Matt Kabelin's dog aging study, um, which, uh, is is is gonna be an exciting readout in 2026.”
Attia says the dog aging study had a funding gap of about $2.5 million, which a group including his patients raised.
“there was a shortfall of about $2.5 million, um, to do the the study that Matt really wanted to do.”
Attia says a small fraction of NAD is consumed by sirtuin enzymes during DNA repair.
“A small fraction of it is used, and it's used by these things called sirtuins that consume NAD as an actual substrate in the process of DNA repair.”
In 2016 Peter Attia traveled to Easter Island, the birthplace of rapamycin, with David Sabatini, Navdeep Chandel and Tim Ferriss.
“in 2016, I went to Easter Island with David Sabatini and Nav Chandel and Tim Ferriss.”
Attia says the Interventions Testing Program, run by Rich Miller, tested resveratrol and found it had no effect on lifespan.
“Rich Miller, who runs the ITP, the interventions testing program, which later tested resveratrol and found that it did, uh, categorically nothing.”
Attia says the one positive resveratrol result came from mice force-fed an extremely high-fat diet, whose fatty livers crowded the chest.
“the investigators took a bizarre mouse model where they force-fed it, uh, an enormously high-fat diet.”
Attia describes the Interventions Testing Program as an NIA-funded study run in triplicate at three independent labs.
“So the ITP is an NIA funded program that runs out of three independent labs.”
Peter Attia says skin sees about a 60 percent reduction in NAD over a lifetime, the largest decline of any tissue.
“skin over the course of your lifetime, will see about a 60% reduction in NAD”
A 2015 PNAS study found whole-blood NAD fell about 10 to 20 percent over four decades while NADH rose by a similar amount.
“In 2015, a study was published in PNAS that looked at NAD levels in whole blood over time, and it found, indeed, NAD levels were going down about 10 to 20% over 4 decades or so.”
Attia says the Interventions Testing Program tested nicotinamide riboside at a very high dose in mice and found no lifespan extension.
“NR was tested, and I believe it was tested at a very robust dose, either 500 or a thousand milligrams per kilogram, and there was no extension of life.”
Attia says acarbose extended mouse lifespan in the Interventions Testing Program without causing lower body weight.
“Acarbose, a drug that inhibits glucose absorption, worked, and, interestingly, didn't require weight loss.”
In a human fatty-liver trial of NR plus a sirtuin activator, Attia says the primary outcome was null and only a subgroup analysis showed liver fat falling from about 20 to 15 percent at the low dose.
“The placebo group averaged 20% at the beginning, 20% at the end, but the single dose of the drug went from 20% to 15%, which was statistically significant.”
Peter Attia says the brand-name rapamycin drug Rapamune was first approved by the FDA in 1999.
“Rapamune is the brand drug, um, that was initially, uh, uh, uh, approved in 1999.”
Attia says generic rapamycin costs about $5 a milligram, so his 8 mg weekly dose costs roughly $40 a week.
“it's about 5 bucks a milligram. That's pretty expensive. So if you're taking 8 milligrams a week, that's 40 bucks a week is probably what I spend on rapamycin.”
A 2014 study by Joan Mannick and Lloyd Klickstein gave people aged 65 and over everolimus and found enhanced immune response to an influenza vaccine, according to Attia.
“they took a group of 65-year-olds and randomized them to either a placebo or different doses and dosing schedules of everolimus, found an enhanced immunity in response to an influenza vaccine”
Peter Attia says the U.S. Nuclear Regulatory Commission recommends staying under 50 millisieverts of radiation a year.
“the NRC recommends that a human being, or at least an American, should expose themselves to less than 50 millisieverts of radiation a year.”
Attia says ambient background radiation at sea level amounts to about 1 millisievert per year.
“just ambient radiation living at sea level is 1 millisievert a year”
Peter Attia says he uses two automated blood pressure cuffs, one from Withings and one from Omron.
“One's called Withings, and the other one's made by a company called Omron O M R O N.”
Peter Attia says the lungs' alveolar air sacs, if spread out, would easily cover a tennis court.
“If you took the alveolar air sacs of the lungs and spread them out, you would easily cover a tennis court.”
Peter Attia says air particles smaller than 2.5 microns (PM 2.5) get straight into the body.
“particulates that are less than 2.5 microns are are getting straight into the body”
Peter Attia says that embryos unable to synthesize cholesterol do not survive.
“So if you cannot synthesize cholesterol, you can't live you, you'll die in utero.”
Peter Attia says the body makes its own cholesterol and that cholesterol eaten in food is largely irrelevant.
“We make all of our own cholesterol, the cholesterol that you eat in food largely irrelevant.”
Peter Attia says LDL-C measures the cholesterol content of LDL particles while ApoB measures their number, and that ApoB predicts cardiovascular risk better.
“LDL C measures the total concentration of cholesterol in the LDLs, apo B measures the number of them, and they're different, but one of them is far superior at predicting risk, and it's apo B.”
Peter Attia says that nearly every man in his family has died prematurely of atherosclerosis.
“where basically every man in my family except one has died of atherosclerosis, and they have all done so very prematurely.”
Peter Attia says MACE, or major adverse cardiac event, is the measure medicine uses to estimate ten-year cardiovascular risk.
“MACE stands for major adverse cardiac event. It is the metric we use in medicine.”
Peter Attia says that for patients with no calcification or soft plaque, he is satisfied with an ApoB near 60 mg/dL, and he targets 30 to 40 mg/dL in higher-risk patients.
“we might be satisfied with a person's apo B being at the fifth percentile of the population, which would be about sixty milligrams per deciliter.”
Peter Attia considers triglycerides above 100 mg/dL elevated, although most laboratories treat up to 150 mg/dL as normal.
“and I consider anything over one hundred to be elevated, even though most laboratory tests would consider normal to be up to 150 milligrams per deciliter.”
Peter Attia describes a patient wearing a continuous glucose monitor whose glucose rose about ten points after starting rosuvastatin, and who recovered when the drug was stopped.
“he pings us like a couple weeks later, and he's like, Man, my glucose is like ten points up consistently from where it has normally been.”
Peter Attia credits Helen Hobbs with discovering mutations in the PCSK9 gene, which codes for a protein that degrades LDL receptors, in people with familial hypercholesterolemia.
“she discovered this mutation in, uh, a gene for PCSK9 that codes for a protein that degrades LDL receptors.”
Peter Attia says he has taken an injectable PCSK9 inhibitor every two weeks since about 2015.
“I probably started in 2015, so it's an injectable drug. I take it every two weeks and it's a called a PCSK9 inhibitor”
Peter Attia recalls a medical school pathology professor saying the most common presentation of a heart attack is death.
“The single most common presentation for a myocardial infarction is death.”
Peter Attia says the kidney receives roughly twenty to twenty-five percent of the blood pumped with each heartbeat, making it sensitive to high blood pressure.
“This is a tiny organ that on every pump of your heart is getting twenty to twenty five of your blood.”
Peter Attia says the evidence, including a JAMA analysis with genetic studies, shows no dose of alcohol is healthy.
“It's actually pretty clear that there is no dose of ethanol that is healthy.”
Peter Attia says the lifetime chance of getting cancer is between one in three and one in four.
“put it this way, somewhere between one in three and one in four chance. Anyone listening to this or watching this is gonna get cancer in their lifetime.”
Peter Attia says over ninety-five percent of cancers arise from acquired somatic mutations, not inherited germline mutations.
“But ninety five plus percent of cancers are not arising from germline mutations, they are arising from somatic mutations or acquired mutations.”
Peter Attia says a waist circumference above half of one's height is a warning sign and a better indicator than body mass index.
“but if your waist circumference is more than fifty of your height, you should be concerned.”