276 ‒ Special episode: Peter on longevity, supplements, protein, fasting, apoB, statins, & more

KEYPOINTS

• 01

  Peter doubts anyone alive today will reach 120–150.

  In this listener-question AMA with Nick Stenson, Peter says he has seen no evidence we can reverse the underlying processes of aging: mitochondrial dysfunction, protein misfolding, DNA damage and repair, or nutrient-sensing breakdown. He calls the gap between the actual science and the hype in media, social media and podcasts enormous, and dismisses aging clocks claiming a 60-year-old is 'really 35.' For a 50-year-old to live another 70 years, a cure for aging would have to arrive within about a dozen years. Assuming today's tools are roughly as good as it gets, he argues, should make you more serious about using them.

• 02

  The realistic prize is one to two extra decades and a stronger 'marginal decade.'

  Peter believes his approach can add perhaps a decade to two of life. Heart disease is the one horseman he sees a clear path to nearly eliminating, through 'ultra-primary prevention' from your 30s: apoB never above 30–40 mg/dL, not even a year of mild hypertension, and constant metabolic health. Cancer, dementia, sarcopenia and arthritis can't be deferred indefinitely. So he fixates on the last decade of life: still able to ruck carrying 10–20 lb, swim half a mile and get out of the pool unaided, and get up off the floor. He sees rapamycin's mTOR inhibition as the most promising incremental drug, partly because it worked even when started late in life in animals.

• 03

  Geroprotective drugs lack biomarkers, so you can't tell if they're working.

  With an ACE inhibitor like lisinopril, blood pressure dropping from 135/85 to 115/75 without dizziness tells you the dose is right. Diet, exercise and sleep all have feedback signals. Drugs aimed at aging itself have none, so you can't know if you're taking too little or too much short of side effects. Peter calls diagnostics an 'unsexy,' underfunded but crucial field. His old fasting routine of 7–10 water-only days each quarter plus 3-day fasts monthly probably cost him about 20 lb of muscle over six years, and he still doesn't know whether it did any good.

• 04

  His supplement list comes with a warning: don't copy it.

  Mornings: Carlson high-EPA fish oil (about 2 g EPA and 1.5 g DHA), dosed to a red-cell omega-3 level of about 12%. Vitamin D, 5,000 IU, which he calls 'picking up a five-dollar bill in front of a tricycle,' since he considers vitamin D trials poorly done. About 1 g of magnesium total from Slow-Mag, magnesium L-threonate (Magtein) and magnesium oxide. Methylfolate and methyl-B12 (Jarrow) to keep homocysteine below 9. B6 cut from 50 mg daily to three times a week because excess can cause neuropathy. A baby aspirin, which he admits is a 'soft call' with weak evidence. Nights: 600 mg ashwagandha (Solgar), 2 g glycine (Thorne) and Magtein. Phosphatidylserine, about 400 mg, for jet lag. Also AG1, in which he discloses he is an investor and adviser, and Pendulum's probiotic, which he's testing on himself after its small 90-day trial showing a 0.6-point A1C drop.

• 05

  Lowering apoB to 30–40 mg/dL takes drugs. Exercise doesn't move it.

  Diet has two levers. Cutting carbohydrates lowers triglycerides, and with them apoB. Cutting saturated fat leads the liver to add LDL receptors and pull more LDL from the blood. Few people reach Peter's target that way. His own baseline apoB is about 90–100 mg/dL, roughly the 50th percentile. He takes Repatha (a PCSK9 inhibitor) plus Nexlizet. Its bempedoic acid component is a prodrug activated only in the liver, so it blocks cholesterol synthesis there alone. Ezetimibe blocks reabsorption of cholesterol from the gut and is the weakest of the three. He has no side effects on this combination.

• 06

  There's rarely a reason for mega-dose statins now.

  Statin efficacy flattens quickly: rosuvastatin delivers about 85% of its maximum apoB reduction at 5 mg, though doses go up to 40 mg. Statins have real, measurable side effects: muscle aches, elevated liver enzymes and insulin resistance. When cost rules out newer drugs, Peter suggests trying low-dose pitavastatin or rosuvastatin to find the best-tolerated option. PCSK9 prices have fallen by more than half, and a twice-yearly injection with a different mechanism is adding price pressure.

• 07

  Energy balance matters most in diet, and sustainability beats perfection.

  Any diet (keto, paleo, Mediterranean, vegan) eaten in excess pushes fat into the liver and viscera. In Peter's clinical experience, people with profound insulin resistance do best cutting carbs to create a deficit. A 7-out-of-10 diet you can keep forever beats a perfect one you'll abandon in three months. Long-lived populations eat very different diets, and Okinawans' advantage fades as they Westernize, which suggests factors like activity, sleep, stress and social ties matter too. Nutrition science is hard because the organism and the intervention are both complex. Long controlled studies, like the Wisconsin and NIA monkey trials, take decades.

• 08

  Protein targets depend on muscle mass and life stage.

  An over-nourished but well-muscled person in a calorie deficit can relax to about 0.6–0.7 g per lb. An over-nourished, under-muscled person needs to keep protein high to build muscle while losing fat. Peter isn't convinced by data linking high protein to mortality under 50, which he attributes to excess calories, confounding and very low absolute risk. Under 50 is the time to build muscle, because after 50 'you're clawing on for dear life.' He targets 150–180 g a day over about four sittings, partly from venison jerky sticks of about 10 g each. He discloses an investment in Maui Nui.