How Your Body Ages From Head to Toe | WIRED

This is an amusing and informative review of aging in many body systems. To me, it illustrates how complex the problem of aging is, and how a given supplement or lifestyle change is unlikely to affect so many degrading systems.

Rapamycin is one holistic approach to slow down the “rust,” but it is not a solution. Individual gene edits won’t do it either, though perhaps they will have partially rejuvenating effects.

This is a good 2018 overview of anti-aging strategies including rapamycin:

This 2019 review covers a more limited range of options (including rapamycin) in more detail,

This 2022 review thoroughly covers supplements and drugs for anti-aging:

More exotic things are on the horizon, like gene editing, Yamanaka factor rejuvenation, plasma exchange or modification, replacement organs, and many others get little or no mention, but could potentially be more important than any drug or lifestyle changes.

For all this complexity, for me, the big three are still exercise, nutrition, and rapamycin, but more is needed.

What are your big three?


I start with mechanisms. For example mitochondrial inefficiency is a mechanism. To fix that there are a number of interventions. One is autophagy. Rapamycin is only one way of encouraging autophagy. There are others.

The other mechanism is transcription improvements. Similarly there are a number of interventions that can improve that.


Addressing mechanisms of aging are some of the biggest levers we have, but they leave a lot of work yet to do. Our bodies were not built to rejuvenate in any complete way, even if we had our teenage metabolism back. If only the rest of our bodies could rejuvenate themselves like the liver seems capable of doing, we could grow younger.

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Liver cells, interestingly, express a citrate transport that has a priority call on citrate in serum.

My 3: sleep (built in repair system), metabolic flexibility (body fatness, energy availability, brain function), athleticism (mito health, body/brain, accident avoidance, cardio health)

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I agree that sleep is huge for healthy aging. I was wondering if you were drawing a distinction between exercise and athleticism?

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It does seem like the solution needs to happen pretty far back the chain of events. It’s really hard and complex to repair a rusted airplane, piece by piece. But if you can protect it from moisture early on with excellent waterproofing and fixing small rust spots as they happen, then it’s relatively simple.


Periodic dosing (or maybe just one brief dosing window) of rapamycin sometime in early maturity might be a kind of “rust-proofing.”

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Yes. I was thinking of exercise as that artificial activity we do to efficiently use our time in using our muscles (lifting weights, jogging, body weight floor drills, etc) vs physical activity / sport that requires skills, vision, hearing, anticipation, planning, movement in multiple planes, reaction to unexpected surfaces or opponent’s behavior, cooperation with teammates, etc. One is obviously better than the other. I have been losing my athleticism as I have been doing more and more mere “exercise”.


The same, I think regular exercise is the singular most important thing for increasing healspan.


I can’t remember if you said anything about taking TRT or not.
But, maybe it’s time to consider TRT and/or DHEA supplementation.

There certainly seems to be an association between hormones and athletic decline. Can we stave off athletic declines as long as possible by normalizing our hormones?

The chart below is my take on the association between TRT and DHEA decline as they relate to athletic performance. The chart is not to scale and is just to show the association between hormone decline and athletic performance.

DHEA is a requirement for many hormones.

“DHEA operates as a natural steroid, akin to other steroids, potentially enhancing muscle mass and physical performance. What sets DHEA apart is its innate nature as a hormone, rendering it a conceivably safer option compared to synthetic steroids”

“The plasma levels of dehydroepiandrosterone (DHEA) and its sulfated form (DHEAS) decline ∼80% between the ages of 25 and 75 yr. Muscle mass and strength also decrease with aging”

Maximizing Gains with DHEA | Ultimate Nutrition.


@desertshores I do not take TRT but I have been supplementing with DHEA for a long time. I have a hormone test winding its way through the system now. I’ll know where I stand on T soon. In any case I don’t think that is the issue. For me it’s a use or lose it problem. I’m as strong (and as muscular) as I’ve ever been but I don’t play touch football or tennis or even pickleball at the moment. I just “exercise”. I used to ski and rock climb and race my bike and hike over rough terrain. Now I ride a stationary bike and lift weights and do “mobility drills”. I’ll be a fit corpse when I trip and fall down the stairs.


Good articles: I just started 50mg DHEA a week ago since my testosterone was on the low side of normal a couple of years ago and I was also hoping that DHEA would reduce my cortisol stress response (and the accompanying higher blood sugars) during exercise.