Longevity medicine is a wide field, and most of it is not what gets marketed. This is a review of what the evidence actually supports, from fitness and blood pressure to the drugs and supplements patients ask about by name.

Patients bring me longevity questions on video, which is how every visit I do happens. It usually arrives as a general question about what I recommend for living longer, followed by one specific thing they read about online. Phosphatidylcholine. Rapamycin. GLP-1 medications.

Here is the part that disappoints almost everybody. The things with the largest measured effect on how long you live are cheap, boring, and nobody can patent them, so nobody sells them. The drugs people ask about by name sit lower on the list, and several sit there with no human results at all. That does not make them worthless. I prescribe GLP-1 receptor agonists and think they are the most important thing to happen to metabolic medicine in my working life. The point is ordering.

What actually works, and it is not a close call

Start with cardiorespiratory fitness, which means how well your heart and lungs move oxygen while you work hard. Nothing else here comes close to it.

Mandsager’s team at Cleveland Clinic followed 122,007 patients who had treadmill tests between 1991 and 2014. The fittest group came out at an adjusted hazard ratio of 0.20 against the least fit (1). A hazard ratio compares the risk in one group against another. Anything under 1.00 means less risk, so 0.20 means the fittest people died at roughly a fifth the rate of the least fit. That is an enormous gap.

That paper also produced the line that being unfit is worse than smoking, and here is the correction. It reported hazard ratios of 1.41 for smoking and 1.40 for diabetes sitting next to 1.41 for below-average fitness (1). Those are similar sizes inside one model. Nobody raced them against each other, and a poor treadmill result is partly a measure of disease nobody has found yet. The pattern does hold up elsewhere, at roughly 14 percent lower death rates for each one-MET gain in fitness (2). A MET is a unit of effort, and one MET is about what your body burns sitting still, so gaining one is real training.

Resistance training is the second lever, and the useful finding is where it stops. Momma pooled dozens of studies and found that any muscle-strengthening work was linked to a 10 to 17 percent lower risk of death, heart disease, cancer and diabetes. The benefit peaks at 30 to 60 minutes a week and flattens after 60 (3). Two half-hour sessions. That is the whole prescription, and the flattening is the part fitness content never mentions, because there is no business in telling somebody they are done.

Grip strength comes at it sideways. In PURE, across 139,691 adults in 17 countries, the death rate rose with a hazard ratio of 1.16 for every 5-kg drop in grip (4). Grip stands in for how much muscle you carry. Nobody should go train their hands.

Nobody ever counted to ten thousand

Paluch pooled 15 cohorts and found the benefit of daily steps levels off around 6,000 to 8,000 for adults 60 and older, and 8,000 to 10,000 under 60 (5).

Here is my one digression. The 10,000 figure has no medical origin whatsoever. It came from a pedometer sold in Japan in 1965, the manpo-kei or ten-thousand-step meter, named partly because the Japanese character for ten thousand looks a bit like a person walking. A marketing name became a health target millions of people feel guilty about missing. Nobody ever checked the math.

The interventions with no sales force

SPRINT assigned people at random to a tight blood pressure goal, under 120 on the top number, against the usual goal of under 140. All-cause mortality, meaning death from any cause, came out at a hazard ratio of 0.73, with an NNT of about 90 over a median of 3.26 years (6). NNT is the number needed to treat. Hold 90 people to the tighter goal for a bit over three years and one of them lives who otherwise would not have. Nothing sold as a longevity supplement has an NNT, because none of them has ever been tested against death.

Quitting smoking gives back more life still. From Jha’s 201,248 US adults, quitting between 25 and 34 gets back about ten years, and quitting in your late fifties still returns four (7).

Sleep follows a U-shaped curve, with the lowest risk near seven hours and the risk climbing faster on the long side, up to a relative risk of 1.37 at ten hours (8). What I want people to stop expecting is a heart benefit from CPAP. SAVE assigned 2,717 adults with moderate-to-severe sleep apnea and known heart disease at random, and the main result came back at HR 1.10, flatly null, which means no difference at all (9). None. CPAP treats symptoms. Say that out loud when you prescribe it.

Then the one physicians skip. Holt-Lunstad’s pooled work put the odds of dying at 1.29 for social isolation and 1.26 for loneliness, with living alone at 1.32 (10). The line about loneliness equalling fifteen cigarettes a day restates those same odds rather than adding a calculation, so hold it loosely.

Diet belongs here too, and PREDIMED is where the honest version lives. Its Mediterranean groups cut the main heart outcome by roughly 30 percent, which is a real result, though the trial was never built to measure death from any cause, and it was pulled and republished in 2018 after an audit found problems with how 1,588 of 7,447 people were assigned (11). Eat that way for your heart. It does not follow that it buys you years.

Weight loss, and what SELECT actually settled

For years there was no good answer on whether losing weight on purpose lowers the death rate. Look AHEAD assigned 5,145 adults with type 2 diabetes at random to an intensive diet and exercise program, held weight loss near 6 percent, and returned a heart outcome of HR 0.95 before stopping for futility (12). Well conducted. Well powered. Null.

SELECT changed that without finishing it. 17,604 adults with overweight or obesity and known heart disease, no diabetes; major heart events hit 6.5 percent on semaglutide against 8.0 on placebo, HR 0.80 (13). All-cause mortality came in at HR 0.81, 95% CI 0.71 to 0.93, and gets quoted everywhere as proof. It is not, and the reason is worth knowing. The trial used hierarchical testing, which means the questions were ranked in advance and answered in order, and once one of them fails, nothing below it counts as proof anymore. That chain broke a step earlier, at heart-related death, HR 0.85, CI 0.71 to 1.01, P=0.07. So the rule bit. So the death result is a strong hint. I think the effect is probably real. I will not tell you it has been proven.

The prescriptions people ask me for by name

GLP-1 receptor agonists are the only drugs here I reach for gladly, and I use them for obesity and its complications. FLOW cut its main kidney outcome to HR 0.76 in 3,533 patients with type 2 diabetes and chronic kidney disease, stopped early because the drug was plainly working, and turned up roughly 20 percent lower all-cause mortality among the secondary results, though I could not confirm the exact confidence interval on that one (14). SURMOUNT-MMO is testing tirzepatide against a combined outcome that includes death from any cause, and it has reported nothing (15). Orforglipron, approved April 2026 as the first pill in the class, has no death data either (16). I prescribe it. I do not pretend it has evidence it does not have.

The catch is muscle. Across these trials, lean tissue was about 45 percent of the weight lost with semaglutide in STEP-1 and about 26 percent with high-dose tirzepatide in SURMOUNT-1 (17). Lean tissue is mostly muscle. Losing close to half your weight as muscle matters in a 68-year-old whose grip is already borderline. It matters a lot. Protein at 1.0 to 1.2 g/kg/day is the geriatric target, and in older patients that is the number I use (18). For most other adults the adequate intake sits higher, and I aim for 80 to 120 grams a day, or 1.6 g/kg/day. Resistance training two to three days a week, covering all major muscle groups, is what decides how much of that muscle survives the loss.

Metformin I would not prescribe to a person without diabetes for longevity. The famous claim is Bannister’s 2014 comparison, which adjusted for nothing: 14.4 deaths per 1,000 person-years among metformin-treated diabetics against 15.2 in matched non-diabetic controls (19). A twenty-year reanalysis found the reverse (20). Most of that first result is confounding by indication, meaning the people who stay on metformin alone were healthier to begin with, in better shape before anyone handed them a pill, so the drug quietly takes credit for a head start it never gave them. TAME was meant to settle it, and as of August 2026 AFAR’s own page still describes it as seeking funding, enrollment not begun (21). Two randomized trials meanwhile found metformin blunting the gains older adults get from exercise, cutting improvements in how well muscle cells make energy and in fitness (22), and losing to placebo on lean mass at 1,700 mg/day over 14 weeks of resistance training (23). Fitness and muscle are the two biggest levers in this piece. Dulling both to chase a result nobody has repeated is a bad trade.

Rapamycin. PEARL assigned 114 adults aged 50 to 85 at random to placebo or 5 or 10 mg of weekly compounded rapamycin for 48 weeks and found it tolerable, with side gains in lean tissue and self-reported pain in women at the higher dose (24). The trial was funded and run by AgelessRx, a longevity telehealth company that sells the thing being studied. Human data on living longer does not exist. I would not write it for this. Senolytics have less. A senolytic is a drug built to clear out worn-out cells that have stopped dividing but keep irritating the tissue around them, and no senolytic has produced any human data on health or lifespan. Everything published so far is safety work (25).

Statins I treat as cholesterol drugs, which is what the guidelines say they are; PREVENTABLE reports in December 2026 on adults over 75 without heart disease (26).

Aspirin is the cleanest example of a longevity assumption failing once somebody randomized it. ASPREE tested low-dose aspirin in healthy older adults for primary prevention, meaning people who had never had a heart attack or a stroke. They died at a higher rate on aspirin, HR 1.14, driven mainly by cancer death, with more major hemorrhage, meaning serious bleeding, and no heart benefit (27). The primary endpoint, which is the single question a trial is built to answer, was years lived without disability, and it showed nothing (28). If you take a daily aspirin with no vascular disease because someone suggested it in 2006, raise it at your next visit.

The supplement aisle, and phosphatidylcholine in particular

NAD+ precursors sell on a mechanism and a biomarker. A biomarker is something you can measure in blood that may or may not track with how you feel or how long you live. Nicotinamide riboside raises whole-blood NAD+ up to 142 percent at 1,000 mg over two weeks, in an open-label study with no clinical endpoint (29). A review of ten NMN trials found the same shape: NAD+ rises, a thin signal on physical performance, nothing resembling a disease or death outcome (30). Tested against thinking and memory in people with mild cognitive impairment, it moved the blood chemistry and nothing else (31).

The ones people tell me they are already on are NAD+ precursors, NMN or NR, and resveratrol. Resveratrol has its own long and contested story, which this post is not going to settle, so read its absence from the rest of this as scope rather than a verdict.

NMN’s legal status is a mess. FDA ruled in November 2022 that it does not count as a dietary supplement, and trade reporting says two FDA letters dated September 29, 2025 reversed that. I have not confirmed those letters against FDA’s own text, so treat the status as unsettled.

Taurine is the most interesting fight in the field. Singh’s 2023 Science paper stretched the median mouse lifespan by 10 to 12 percent and reported that taurine in the blood falls with age in humans, monkeys and mice (32). That second claim is what created the product. An NIA-led group then found taurine flat or rising with age across three human groups plus primates and mice (33), and a separate group measuring 137 men aged 20 to 93 found no link between taurine and age, muscle, strength or how well muscle cells make energy (34). The mouse result stands unchallenged. The human claim underneath the marketing failed to repeat. Twice. No trial has tested taurine against a real human outcome. Anyone selling you certainty either way has not read all three papers.

Phosphatidylcholine earns its own answer, because the real story beats the marketing one. It is a fat molecule and one of the main ways we get choline from food, sold in pills for memory and cell health, and injected as a fat-dissolving product. Pill trials of phosphatidylcholine and lecithin have not helped memory in Alzheimer’s disease, the supporting work on lifespan sits in worms and mice, and no human trial measures anything that matters.

The case against it is better built than the case for it. Choline, phosphatidylcholine and carnitine feed gut bacteria that make a compound called trimethylamine, which the liver turns into TMAO. Tang followed 4,007 heart patients and found that high TMAO went with more heart attacks and strokes (35), building on Wang’s 2011 Nature paper showing that gut bacteria breaking down phosphatidylcholine drives artery disease in animals (36). Read that honestly and the research against phosphatidylcholine pills is stronger than the research for them. I would not take it. The injected version is worse. FDA warns about phosphatidylcholine and sodium deoxycholate products sold online as Aqualyx, Lipodissolve and Kabelline, and the only approved injection for fat reduction is deoxycholic acid on its own, for fat under the chin (37).

The money I would rather you did not spend

Injectable peptides bought online are the clearest line I draw. FDA put several, BPC-157 and epitalon among them, into category 2 of its bulk drug substances list in September 2023, which flags a real safety risk and blocks pharmacies from mixing them up for patients (38). There has been plenty of trade reporting that HHS moved to pull most of them back off that list. I have not confirmed any of it against FDA’s own text, so I am not going to tell you the rules changed. Coming off a restricted list would not be approval anyway. It never was.

I have seen videos online of people advocating injecting peptides, and it makes me uneasy.

Stem cell and exosome clinics have a legal record anyone can read. A federal court ruled against US Stem Cell Clinic in 2019, finding its product adulterated and misbranded, which are the legal terms for failing quality standards and being sold under a false label, and the reported harms include blindness. FDA states there is no approved exosome product for any medical use in this country (39). Young plasma got its own February 2019 FDA notice: no convincing evidence of benefit, against risks including fluid overload, TRALI, which is a serious lung injury, and catching an infection from the donor (40).

Growth hormone marketed for aging can put you in criminal court. 21 U.S.C. §333(e) makes it a federal felony to hand out hGH for anything other than an FDA-approved use in a diagnosed disease, and FDA counts writing the prescription as handing it out (41). It is the only drug in the code carrying that rule. The pitch still traces to Rudman’s 1990 NEJM paper: 21 men, six months, no placebo group, an 8.8 percent rise in lean body mass (42). Nobody counted deaths, and nobody was blinded. NEJM said in 2003 that consumers who meet those citations are being misled (43). Still doing sales work.

Consumer epigenetic age tests belong in the entertainment column. A 2025 preprint reports that running one sample twice can give answers as much as nine years apart on some clocks, and the reliability problem shows up in peer-reviewed work too (44). If your number moves three years after you start a supplement, you measured the test.

Full-body MRI in people with no symptoms is the expensive one. Scans turn up a confirmed cancer roughly 1.1 to 1.5 percent of the time, while about 95 percent of healthy adults show an incidental finding, meaning something the scan spots by accident, and around 91 percent of those turn out to mean nothing (45). Nine in ten. Nothing. What it reliably produces is a repeat MRI, a biopsy of something harmless, and months of fear. Skip it.

For patients, and for the clinicians reading over their shoulder

If you are a patient, work the list in the order the effect sizes come in. Blood pressure to target, which on my end means you own a cuff and bring me the readings, since I cannot take them from here. Quit smoking at any age, because the payoff is measured in years rather than percentage points. Build an aerobic base and lift something twice a week. Then, with whatever money and attention is left over, consider a supplement, and ask one question before you buy it: what did the trial actually measure? If the answer is a blood level, a clock or a marker, it did not measure your life. That question alone empties most of the aisle.

If you are a clinician, the awkward part of this field is that our best-evidenced longevity drugs are ones we already prescribe under other names. Blood pressure drugs, statins, GLP-1 receptor agonists, quit-smoking therapy. Patients arrive on video already carrying things they bought from direct-to-consumer platforms, so ask what they are taking without an eyebrow, because a patient who feels judged stops telling you. Get the compounded rapamycin, the peptide vial and the NMN into the chart and screen interactions properly. When you quote SELECT, quote the hierarchical testing failure along with it.

The Bottom Line

The gap between the best-proven ways to live longer and the most heavily marketed ones runs opposite to the ad money. Cardiorespiratory fitness, blood pressure control, and never picking up another cigarette sit at the top, with effects no capsule has come near.

GLP-1 receptor agonists have real outcome data and a real reason to use them. Metformin for longevity in people without diabetes rests on a weak comparison nobody randomized, plus two randomized trials showing it gets in the way of exercise. Rapamycin is interesting and unproven in humans. Senolytics have nothing at all. Aspirin in healthy older adults who had never had a heart attack made things measurably worse. NAD+ precursors move a blood level nobody has shown you should care about, the human claim behind taurine failed to repeat, and phosphatidylcholine has better research against it than for it.

Buy the used bike before you buy the peptide. If you want one thing to do this week, it does not cost anything.

Scott Rennie, D.O.
Board Certified in Obesity Medicine and Family Medicine

This blog is for educational purposes only and does not constitute individual medical advice. Always consult your own physician before making changes to your health, medications, or treatment plan.

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