I imagine this was posted to this forum last year, since they say in the piece at the end, “An earlier version of this article was published in August 2024.”
Glancing at the paper they reference (which I recall hearing about months ago), I see that for the first peak (around age 45 or so) some of the microbiome patterns peak earlier than the others (e.g. the oral microbiome peaks around age 41). I wouldn’t wager that they cause the other peaks, but perhaps these microbiomes pick up on a subtle signal missing from the other data (proteomics, lipidomics, transcriptomics, etc.) that causes shifts in their distributions. Of course it could also be that their peaks are unrelated to the others (proteomics, lipidomics, etc.), that it’s all just an interesting coincidence.
Perhaps AI models will soon be able to read a paper like this, digest it, and then to theorize about how to delay these peaks (assuming they truly correspond to aging bursts), e.g. by recommending diet, supplements, and (old, repurposed) drugs. In fact, maybe models can already do this. I didn’t bother feeding it into o3 or DeepResearch or Gemini 2.5 Pro to find out… (And the authors of the piece couldn’t have, either, since their paper came out before these powerful models were available!)
The PR / paper…
Gut metabolites that have been isolated and tested in efficacy for Alzheimer’s treatment require tryptophan be metabolized, and this process is harmed by shifts in L-tryptophan to L-kynurenine ratio.
I made a comment about it here that I think is deeply relevant to this post: The four best longevity interventions? - #179 by AustraliaLongevity
It’s my belief that as we move past these aging spikes at early 40’s… then early 60’s the benefit of rapamycin will be blunted on how much benefit you can get. Once you past these aging periods you can get only so much body repair.
This is based on my own N=1 and from the many testimonials I have read on this site… some advanced aged rapamycin users seemingly are baffled at not getting the same benefits in visceral fat loss and general well-being.
I feel lucky that I started my health reversal at 60 years with significant weight loss (from walking and less calories) and regular gym… muscle resistance workout days… followed by weekly TRT injections at age 61 years and then weekly 6 mg rapamycin at 62 years. Possibly benefiting, from my self correcting life-style (diet and exercise) and hitting rapamycin and TRT at the last possible moments before that mid 60’s spike hit.
Much like Matt Kaeberlein says on cancers and alzheimer’s… if you start rapamycin before you have cancer or alzheimer’s… you won’t ever get them.
Starting after you have cancer or alzheimer’s… you will get some reversal benefits. But not as good as preventing them.
My thoughts on the aging spikes… using rapamycin before the spikes you get a good age reversal… after the spikes… you get some benefits… but not as much if you started before the spike.
Just my observation on this site from others reports and my qualitative assessment. 
Yes. However, I do wonder if there are individual differences. There is the concept of biological aging. It is possible that people age at different rates. So it’s theoretically possible that for some those “faster aging” time periods may come sooner or later.
Oh yeah definitely… different phenotypes and genetics.
My message was in general. Sooner after 30 years is better.
Considering 30 years is one’s peek… like the T score for bone density is at 30 years.
It could be that these aging periods cannot be reversed, similar to returning to childhood or something; however, I imagine these later ones (age around 40 and 60) might be different. e.g. some of these later changes might be affected by the immune system; and we know that, for example, the thymus can be regenerated (it starts to decline in one’s early teens).
Looking at the more recent paper above that @AlexKChen links to, I see they mention the gene SHISA5 (or the protein) as a particularly important one regarding those aging spikes. I was curious what effect the immune system might have on this gene, so asked o3:
…
Like you, I also am careful about diet and exercise. In fact, I’m kind of a “gym bro”.
Blood protein signatures change across lifespan | National Institutes of Health (NIH) says 3 different waves… (I remember this paper the most)
Great article. Thanks
My own observations (anecdotally, of course) are that, at the ages around 60 and 81 - 82, there are rapid negative changes in the human physiology. My own speculation is that the observed changes in proteins forgo the observable negative physiological changes. Especially the later wave (78 - 82) can be detrimental and push people over the cliff to degenerative agerelated diseases.
“In people in their 40s, significant changes were seen in the number of molecules related to alcohol, caffeine and lipid metabolism; cardiovascular disease; and skin and muscle. In those in their 60s, changes were related to carbohydrate and caffeine metabolism, immune regulation, kidney function, cardiovascular disease, and skin and muscle.”
The above from Joseph’s paper. Massive biomolecular shifts occur in our 40s and 60s, Stanford Medicine researchers find
Aging involves many things, like the accumulation of damaged, dysfunctional, or toxic proteins. Oxidatively damaged proteins, for example, are considered a likely common cause of (or contribution to) aging and age-related diseases. These protein modifications can disrupt protein structure and function, leading to cellular and tissue dysfunction which later on manifests in observable decreased functions and also in increased states of different disease. I started rapamycin at 60 but starting rapamycin a few years before 60 would (according to the above) have been optimal for me. If I was younger, I would have started at around 30-35.
Exactly… the sooner after 30 years… perhaps in smaller doses… say 2 mg weekly… the better. Glad I started at 62… already in pretty good health at the time. Wish I had started at 50 or sooner.
But, as the old adage goes… better late then never.
I can attribute the repairs from dysphagia… crepey skin, allergies… visceral fat… increased strength and memory to rapamycin. I also have a pretty robust immunity to disease and I heal quickly.
I had a family reunion this past week… my 4 genetics siblings could see I seemed decades younger to them. All are planning to start rapamycin. Hahaha. Good for them.
Three waves but 2 specific times separate those 3 waves
wave 1 = birth to time 1
wave 2 = time 1 to time 2
wave 3 = time 2 to the end
I think there is some speculation lately there may be a 4th wave, so a 3rd “time” in the 70’s