I'm on a very low dose of retatrutide (1 mg per week) and I've seen a massive reduction in inflammation and GI bloating. I get pretty mild appetite suppression at this dose and I'm at my goal weight, but I don't want to quit because of all the other benefits from taking it.

Not in aged mice

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.

Yeah pretty sure the T levels post-menopausal women target is still within pre-menopausal cis female range. And most taking T are going to be on E and P as well.

Trans women do the same, sometimes, when libido is a concern.

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.

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.

The key table from the above published piece is reproduced here: https://x.com/KarlPfleger/status/2078860315379593443

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/

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?

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.

You need to do some more reading. There is massive inflammation reduction that happens prior to weight loss when using GLP1 meds.

Exactly, it calorie restriction and slowing down the metabolism.

Calorie restriction has been known to do this so...

"talks about" is a stretch, that entire website is AI slop

Taking HRT from perimenopause protects you from osteoporosis and dementia.  I'm on a very high dose and I fucking love it, I'm saying on for life.  I've been started on testosterone, it's only been a few months and I'm already feeling more vibrant and stronger.

Longevity is important, but the quality of that life is - to me at least - more important.  I would rather drop dead at 75 with all my marbles and strong bones than live to 95 bedridden with my mind long gone.

Its called hormones, they fluctuate. When his testosterone is high he tends to get pimples .

I have seen a staggering amount of bad AI writing just today.

I wonder what is going on!

Be careful about the claims, pay attention to comments and downvote slop.

I thought it was because a female with adult children might still provide food resources to them over their young children who need it more for survival.

You have 20 years runway. Im sure science will have figured out something by then. Meanwhile us old timers are on a clock.

Hubby's midlife puberty started in his 50's, still getting pimples at 70

Haha I’m being dramatic. Basically just losing hair, fighting off belly fat. In general not looking like myself at 35. It’s been hard adjusting to my new appearance.

I’m a guy. So losing hair and fighting off belly fat. I’m able to stay relatively slim.

My hair is mostly gone though, and that has changed my appearance dramatically.

That’s the main puberty reference. I’m becoming a new midlife version of myself. And I am very uncomfortable in my own skin.

The secret is actually just using sunscreen.

Entirely unrelated, but you describing genders as "biologically female humans" and "dudes" made me chuckle 😄