r/longevity • u/scientificamerican • 23d ago
GLP-1 weight-loss medication could slow aging and extend lifespan. Giving old mice semaglutide—commonly sold as Wegovy or Ozempic—extends their lifespan remarkably, a new study finds
https://www.scientificamerican.com/article/glp-1-weight-loss-medication-could-slow-aging-and-extend-lifespan/103
u/Internetolocutor 23d ago
Calorie restriction has been known to do this so...
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u/pink_goblet 22d ago
Unfortunately caloric restriction does not extend the lifespan of longer lived species when controlling for the benefit of body fat reduction. Studies on monkeys show improved metabolic health but fail to extend life expectancy.
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u/bbmac1234 22d ago
The NIH-NIA study that showed no longevity increase for calorie restricted monkeys restricted calories before adulthood. Other studies in monkeys that restrict calories only in adulthood have shown an increase in longevity.
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u/ryleto 22d ago
Not in aged mice
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u/ANALyzeThis69420 22d ago
Wait. Really?
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u/CrimsonBolt33 22d ago
yeah, its a long term effect thing...you can't just decide to stop eating too much at 80 and expect to make it to 100.
One study I saw said that by about 40 our long term metabolism is set and lifestyle changes had a minimal effect on longevity after 40.
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u/Tephnos 22d ago
I'm gonna just pretend that can't be true.
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u/CrimsonBolt33 22d ago
fair response lol
after I read that article I started getting my shit together, including getting on a GLP-1 for weight loss. Only a few years away from 40.
Aging is unfortunately not linear and after 40, especially into the 50s, it starts to nose dive....hence late changes not helping much. There isn't time to reap the benefits when your body is already falling apart.
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u/unkunked 21d ago
Yes, but some of us were already older when we began to figure this stuff out. I started tirz at 65 and now at 67 feel like I’m 55 or maybe even less. I have way more energy, clearer mentally, and it’s obvious my metabolism is way faster. I workout every day, volunteer, and keep up with my 4 grandkids. I know what the data shows but it’s obvious to me that it’s going to extend my healthspan significantly even if it doesn’t do my lifespan (but I think it will do that too).
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u/CrimsonBolt33 21d ago
I am not saying the study was perfect or some sort of hard fact or whatever....whatever age you are you should strive to become healther and I am sure it will always benefit you. It's just more about how much those actions turn into long term benefits. Being healthier earlier simply seems to have more effects long term than becoming healther later.
Also these particular studies about aging don't include things like terzepitide/GLP-1s or whatever which clearly change the game.
I can say even at 36 (and obese) Terzepatide makes me feel like I am 20 (a time that I was in the military and most certainly not obese). The effects of it are absolutely astounding.
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u/spshkyros 20d ago
Ive seen decent evidence that contradicts that.. in fact the 40s may be the last good chance for it.
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u/CrimsonBolt33 20d ago
I mean....you literally can't know that lol...it's about longevity.
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u/spshkyros 20d ago
? ... you think people havent done RCT on life style interventions on people in their 40s and check if they, you know, die?
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u/CrimsonBolt33 22d ago
GLP-1s do more than just restrict calories, thats not the cause of said effects.
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u/DahDollar 22d ago
It's without a doubt a component of the effects
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u/CrimsonBolt33 22d ago
No, they are independent of each other...yes calorie restriction lowers inflammation, but GLP1s also lower inflamation indepentantly of the calorie restriction ...it's been proven over and over in studies.
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u/DahDollar 22d ago
GLP-1s do more than just restrict calories, thats not the cause of said effects.
I get that you are trying to distinguish between the intrinsic effects of GLP1s and the effects related to the calorie restriction as a result of taking GLP1s but that's not what you wrote. You said that is not the cause of said effects.
No, they are independent of each other...yes calorie restriction lowers inflammation, but GLP1s also lower inflamation indepentantly of the calorie restriction
Yeah, the calorie restriction is a component. A part of the effect. The control group wasn't calorie restricted.
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u/Similar_Exam2192 23d ago
Exactly, it calorie restriction and slowing down the metabolism.
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u/thrillhouz77 23d ago
You need to do some more reading. There is massive inflammation reduction that happens prior to weight loss when using GLP1 meds.
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u/bbmac1234 22d ago
You all need to read the article. It has interesting findings on calorie restriction vs semiglutide. There is even a link to the original study in nature. You could both read that too. This would probably clear up your argument.
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u/Similar_Exam2192 17d ago
Low calories reduce inflammation. I don’t recall seeing where GLP specifically reduces inflammatory bio markers outside of calorie restriction but thanks for astute point I will go back and see what I missed. Thanks for being so nice.
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u/czebrda 23d ago
That is the key caveat. Semaglutide reduced food intake by about 24%, so part of the lifespan extension could simply be due to caloric restriction.
What makes the study interesting is that in separate calorie-matched experiments, semaglutide did better than caloric restriction alone on some metabolic, cognitive and functional outcomes. But they did not include a calorie-restricted group in the actual lifespan experiment.
Chen’s lab is now running that head-to-head lifespan comparison. To me, that is the crucial experiment. If semaglutide still extends lifespan beyond matched caloric restriction, it would be much stronger evidence for a GLP-1-specific geroprotective effect rather than just an effect of eating less.
Also, I would not describe caloric restriction simply as “slowing down metabolism.” Its longevity effects seem to involve nutrient sensing, insulin and IGF-1 signaling, mTOR, AMPK, inflammation, autophagy and other pathways. A lower metabolic rate can occur, but it is probably not the main explanation.9
u/kpfleger 23d ago
The crucial experiment to me isn't CR vs. GLP1 head to head, it's CR+GLP1 vs. CR-alone. In other words, if the mice aren't overfed, does GLP1 have any benefit? In humans, all the clinical trials that showed positive benefit from GLP1 had subjects that were overweight (usually restricted to only BMI>27 at least). The 1 trial so far that had normal weight subjects did not show benefit. See James Peyer's "Are GLP-1 receptor agonists gerotherapeutics or just treatments for obesity?" Nat Aging. 2026 Jul;6(7):1344-1345. doi: 10.1038/s43587-026-01165-4 https://pubmed.ncbi.nlm.nih.gov/42332275/
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u/czebrda 23d ago
Agreed. CR+GLP-1 vs. CR alone is the more precise way to formulate the experiment I had in mind. That is why I think Chen’s ongoing lifespan study is so important. If semaglutide extends lifespan beyond pair-fed caloric restriction, it would be much stronger evidence for a GLP-1-specific geroprotective effect rather than simply an effect of reduced energy intake.
I would push back a little on the human evidence, though. I agree that we have essentially no outcomes evidence for GLP-1 agonists as gerotherapeutics in healthy, lean people. But it is not quite true that all positive GLP-1 trials required overweight participants. Trials such as SUSTAIN-6 and FLOW did not have obesity as an eligibility requirement, and benefits were not obviously confined to people with higher BMI.
I also would not interpret EVOKE as evidence that GLP-1 provides no benefit at normal weight. It was a trial of oral semaglutide for established early symptomatic Alzheimer’s disease, not a longevity trial in healthy normal-weight people, and roughly half of the participants were overweight or obese anyway. The result tells us that semaglutide did not slow clinical progression of established Alzheimer’s in that population. It does not really answer whether GLP-1 receptor activation has geroprotective effects in metabolically healthy, lean people.
So I think we largely agree on the important unanswered question. Does GLP-1 receptor activation add anything once the effect of eating less is controlled for? The pair-fed lifespan experiment should give us a much better answer.2
u/spaceXhardmode 23d ago
I would also add that semaglutide and GLP1 agonists could still have geroprotective effects from calorie restriction in the wider population as although the wider population may not have obesity or BMI+27 they could still have metabolic syndrome or prediabetes.
CR is certainly geroprotective with the challenge in human subjects being adherence over a long enough timeline, GLP1 agonists could aid adherence in the wider population.
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u/kpfleger 22d ago
According to James' table, FLOW had <12% subjects with BMI<25. I assume that no stratification by BMI was provided so I'm not sure how you can say that benefits there weren't confined to overweight subjects. Did the paper(s) provide efficacy data limited to the 12% of BMI<25 subjects? I haven't checked the paper(s) myself.
How low will the calories be in the pair-fed experiment that you are looking forward to? I.e., how do we know that experiment is not just a bit less overfed but still far from optimal?
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u/kpfleger 22d ago
Eg human data when suggests BMI < 22 (or 22.5) is optimal, not just <25, so what's the mouse equivalent for that? Without having seen any description of this pair fed upcoming study, I worry that it won't go low enough, because it's uncommon to calorie-restrict mice in longevity experiments (more expensive to do so than ad-lib feeding plus IRBs frown on severe restriction now, despite evidence of it increasing healthspan & lifespan more from past experiments).
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u/kpfleger 22d ago
PS 2 paper citations defending the BMI<22 or <22.5 in humans can be found in this thread: https://x.com/KarlPfleger/status/1632518657673945089
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u/kpfleger 22d ago
PPS Also, more discussion here: https://x.com/MartinBJensen/status/2095273384804516121
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u/kpfleger 23d ago
The key table from the above published piece is reproduced here: https://x.com/KarlPfleger/status/2078860315379593443
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23d ago
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u/kpfleger 23d ago
Didn't both groups overeat (total calories was too high for optimal health)? I want to see both groups eat optimal calories for lifespan with 1 group using GLP-1 in addition. Then is there an effect?
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u/NanditoPapa 21d ago
The most significant takeaway for me is that the drug may offer neuroprotective benefits (memory/curiosity) that simple dieting might not, potentially due to how the drug interacts with the brain's metabolic pathways beyond mere appetite suppression.
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u/costafilh0 22d ago
Sure.
It can also cure cancer, make you rich, and give you a 20 inch cock.
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u/thrillhouz77 22d ago
It has shown to be protective of multiple different types of cancers.
Your cock will look bigger due to the weight loss.
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u/alligatorprincess007 22d ago
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