Great video Brett! Reminds me of my days in the circus! 
1 Like
Hard to keep it five, but here it goes.
- Exercise (3 rigorous with weights and cardio and 2 with mainly cardio) per week
- Clean diet with sufficient protein and limited overall calories
- Rapamycin (3 months on followed by 3 off)
- Appropriate supplements (Omega-3, D3/K2, Astaxanthin, Mg, Glycine, Taurine, Creatine, etc.)
- 7 or more hours of sleep
6 Likes
Did you start rapamycin? I just started at 3mg this Monday.
1 Like
Certainly. I started January of this year with the Biocon/Eris rapamycin 3mg week one, 4mg week two, 5mg week three, 6mg week four and then continued the 6mg once weekly until the beginning of April. At that point I tested my rapa levels at 49-50 hours past the 6mg dose and got a reading of 5.6 ng/mL , which is apparently considered high. I took the weekly dose on an empty stomach in the morning. Since early April I have stopped taking rapamycin on account of dental surgery and the implantation of two titanium posts in preparation for crowns. I will resume taking 6mg once weekly rapamycin this coming Saturday 05/24/25. But this time I will be taking 6mg a week of the Zydus sirolimus brand for three weeks and again I’ll test blood levels at 49-50 hours at the same lab, just to see if there is any difference between the brands. After that I’ll continue back with the Biocon/Eris brand.
I have had no negative side effects that I can identify or see in basic biomarkers, except some acne pimples, some 3-4, weekly on my scalp and face area. Positive effects were that I no longer experienced any exercise related aches and pains in my joints or tendons.
4 Likes
No longer any exercise related aches or pains? Fantastic! So encouraging! May I ask your age, please? If you would rather keep that personal information private, that is completely understood. I ask because my life history has involved fairly consistent pain of one kind or another. In my thirties and forties, I ran long distances (the half marathon was my favourite race distance). Arthritis, etc. made that form of exercise difficult to maintain. Even joint replacement surgery resulted in an inner scar tissue (“Arthrofibrosis”) which made movement even more painful and difficult. An accomplished surgeon (and hopefully the Rapamycin) may allow me to return to healthy levels of exercise. This revision surgeon has improved pain levels and ability to move more normally (improved my knee range of motion from 40 degrees to 90 degrees. I have added Rapamycin to the recovery protocol in hopes of being able to return to a more active life. Thank you for your informative post. I am very grateful to have found this website, and the wonderful knowledge base here. This gives me hope.
1 Like
I am 67 years old, male. It took some weeks before I felt the positive effects of rapamycin, with fewer aches and pains. One strange effect, which I don’t understand the mechanism of, is that apparently my exercise capacity is also increased insofar as jogging - I spontaneously jog at a faster pace. This was noticed by my wife with whom I jog. I’m speculating that the diminished aches might make me run at a faster speed, though I admit it’s unlikely, as I was not limited by aches in the pace my jogging before rapamycin. It’s as if my conditioning was also superior, but again, I can’t think of why that would be physiologically a result of rapamycin. Less of aches and pains however, I can understand: lower inflammatory state in the tissues, and amelioration of fibrosis and therefore greater joint flexibility and range. I also do very intense squatting and have definitely noticed that I can do it with less subjective strain on my knees.
But one caveat: I have never been diagnosed with arthritis, nor subjectively have I felt any definite effects of osteoarthritis - occasional feeling of inflammation in the small joints of my fingers, but that’s intermittent, and happens only from time to time. It is possible that rapamycin might have a greater effect with arthritis, although personal testimonials from the users of this site seem to indicate that it’s not a universal effect, with many reporting no impact.
5 Likes
The theory of mitophagy is that it recycles selectively the less efficient mitochondria sometimes splitting mitochondria into sections and recycling the sections that are less efficiency.
Hence it is quite possible that on average your muscles are able to produce more power.
4 Likes
A year ago, my answer would have been different. Today, when considering healthy males 70 years of age and older, I believe that a scientifically managed musculoskeletal, cardiovascular, and balance and agility exercise program can account for more variance in longevity, along with and less downside risk, than biochemical interventions. In the world of daily life, of course, a multimodal approach that balances, fitness, sleep, diet, stress, and geroprotectives seems smartest. On this point, I agree with Attia: it is likely unjustified to prioritize possibly geroprotective supplements until one has first achieved adequate metrics representing muscle development, flexibility and agility, and VO2max.
One’s participation in geroprotective supplements should reflect their risk tolerance and their results. This is vary generic, however.
5 Likes
That’s interersting RobTuck. I am not sure I understand the thrust of your post, it’s possible that I don’t, as it’s just not very clear (to me 
). I’m gathering that you gradually evolved your thinking from an emphasis on supplements and geroprotective interventions (medications etc.) toward the primary focus being on getting to optimal healthspan and lifespan through lifestyle interventions first and foremost - exercise + diet(?). Again, if I misunderstood, I apologize.
In any case, regardless of whether you hold that view, it’s a view that’s quite prevalent in health focused circles. There are quite a few such advocates on this site (I’m not saying you are one of them!), the ethos can be summed up as “accomplish all your health goals, healthspan and lifespan through lifestyle efforts, without drugs if you can help it”. It’s part of what I call the “naturalistic fallacy”, which sees “nature” as providing optimal solutions and human intervention can only degrade the result (again - not saying that’s you, RobTuck!).
I think it’s a view worth examining. As happens, my journey has been in the opposite direction: starting out in my youth as holding that lifestyle adjustments should be the primary approach with supplements, drugs and other interventions to be complementary, to my present view that while lifestyle optimization is a good first step, it is liable to be a very minor part of true healthspan/lifespan extension, and one should really focus on meds, supps and other interventions.
In practical terms: I don’t see any reason to go much beyond avoiding destructive lifestyle choices. So, for example, in exercise, step #1 would be avoiding sedentary behavior. You can hit 80%-90% of exercise health/longevity benefits with a relatively modest investment of time and effort. I see zero reason to pour massive amounts of time into exercise that gets you asymptotically closer to “perfect”. The squeeze is just not worth the juice. Looking at the evidence, my conclusion is that the last paltry few percetage points are bought at an unreasonably great investment in time and effort. If you enjoy exercise - fine, you do it because it enhances your QOL, and better health is a byproduct, in which case it is not an “investment” as much as the whole point of it. But I - like many others - don’t enjoy exercise and see any investment of time and effort into it, as an opportunity cost - I’d rather be doing something else, it’s a question of QOL. I exercise to live, not the other way around. Same with diet. Luckily(?) for me I naturally enjoy an extremely healthy diet, it makes me feel good and I find pleasure in it - but if I had the same predisposition as toward exercise, i.e. I enjoyed SAD or were a fast-food addict, I’d have the same attitude - just get the big picture OK, a roughly healthy diet, without the extremes of self-deprivation.
So the bottom line, I believe that doing mostly OK in the basics of lifestyle gets you 80%-90% of optimal health, and if you were to dedicate yourself to a fanatical optimization regimen, you’d barely sqeeze out enough extra healthspan/lifespan to notice. In an analogy I’ve given once before - if your aim is to move between Los Angeles and NY as fast as possible, running will only take you so far, you can run a little faster with extensive training, but even elite level athletes will only make marginal progress - you need a horse, a car, an airplane, a rocket and other tools of civilization. So, my attitude is - training enough to being able to run at a reasonable and comfortable speed is only going to take you so far, for real speed, I’ll have to focus on the tools of civilization. Thus my motivation to squeeze out another 2% of speed from my running at the cost of spending 20% of my lifetime exercising is exactly zero.
And that’s my feeling about the balance between lifestyle vs medical interventions. Do enough with lifestyle to not set yourself back, but your real gains are only going to come from science. So an inversion of the naturalist - get your meds and geroscientific interventions in order and for lifestyle just make sure you’re not being destructive.
Real life examples of interventions would be: a healthy lifestyle is good for the eyes. But no matter how many carrots and cups of kale you consume, and how many hours you spend running in the mountains, age will degrade your eyes at almost the same rate as someone who has just a reasonable diet and exercise program. You will develop cataracts, and your lenses will become stiff, your vision less sharp and so on. Meanwile, you can replace your lenses with IOL surgery and have a vision at 90 years old that most 20 year old would envy. Running vs a rocket ride.
It makes no sense to harden your body against blows by rigorous exercise (MMA fighters and bone rolling exercises), if you have access to guards - helmets, gloves, shinguards etc. The latter will be infinitely more protective than any amount of hardening exercise.
Here is a thought provoking statement by Brian Kennedy in an interview on Matt Kaeberlein’s podcast. In essence, when they looked through NHANES data (confirmed by UK Biobank data), they discovered an interesting phenomenon: there were those people who naturally had their key biomarkers within normative range, just by themselves (perhaps also assisted by excellent diet and exercise etc.), and then there were those who had their biomarkers brought to within “normal” range through certain medications (lipid, glucose, BP etc.), i.e., they were originally out of range (in “inferior” health) and then they matched the biomarkers of the “naturalists” only thanks to modern medications. Well, it transpired that the folks who got there through medications had ultimately better outcomes, and were biologically younger! This shows the power of medications, and thinking about it, perhaps it’s not surprising at all. Here’s the discussion, starting at minute 12:19:
This may seem like a paradox, but it’s not, if you think about it. For many people (me included), no amount of healthy living diet and exercise can get my lipids to within norm. Same (for me) for blood glucose. Blood pressure (me again). My genetic predisposition and aging prevents that. And for others, they can reach their biomarker targets through lifestyle means, but sometimes have to take heroic measures. But meds can get me there - and better. I can probably get better lipid numbers through medication than someone else can with no matter how good a lifestyle. Because while the lifestyle guy is running their guts out, he’s still on a long journey and I can zip past him with ease in my Lambo.
What’s notable is that these suboptimal guys got to a better place with meds than the optimal guys with just lifestyle. So you can start off with OK diet and OK exercise and still outpace the guy with optimal diet and exercise just with the use of meds.
There are of course more powerful agents that we hope will give us a much bigger boost than statins, ARBs, SGLT2i, etc. - like rapamycin. Because no matter how good the diet and lifestyle of those mice in the ITP, there was no way they could match rapamycin.
We are gambling that the same holds true for humans.
And therefore my approach is to say - I’ll exercise “enough”, and spend my time living my life to my satisfaction. I’ll eat healthily “enough”, but not worry about the occasional cake or glass of wine. I don’t need to be an ascetic lifestyle purist or some kind of monk, priest of healthy living. I can just be “OK”. My real focus is - and in my view should be - all those other things, the meds, the supps, the bionics, the Lambo, and the rocket. Only the latter will make the real difference.
13 Likes
Great post @CronosTempi. You raise many important points and I agree with many of them. Where we might disagree – more an unresolved and very complex empirical question to me – goes to the amount of variance accounted for and limits set by what might be called non-pharmaceutical foundational health interventions and their associated metrics. I see this issue as far from resolved and almost certainly partially determined by individual differences, including personal preference. As one small example of the preference issue, irrespective of my lengthy supplement regimen, I absolutely enjoy how I feel when I lift weights, hike steep mountains, and eat and sleep well and stress free. The concept of opportunity cost or sacrifice do not apply for me and for pretty much every high fitness person I know. I would engage in the foundational life extension activities at the same level even if hard data suggested zero life extension because it would be difficult to overstate the quality of life extension.
3 Likes
The evidence from anecdote on this forum and from my own optician is that it is possible to improve the homeostasis of the lens in Homo Sapiens.
2 Likes
On this note, @CronosTempi
I go to a mad scientist optometrist who has a room full of high tech equipment, and he does believe diet can influence your eyes.
I’ve shared this before, but when I first went to him, and he did not know I was vegan, he said you eat a lot of greens, don’t you? I was shocked he could tell! He also said I can watch screens late at night because my eyes are naturally filtering everything I need. I checked with other patients, including my husband who was there that day, and he did not say this to any of them. I asked them because I was convinced this was a line and only meant to impress people :).
I was there again last month, and with a different crazy machine, while he could find early cataracts in my husband, he announced I have zero trace of anything and I’ll probably never get them… and to your point, I was not really happy about this because then I won’t be getting the great new lenses I’ve been looking forward to!
You’ll have to check with me in 20 years to see if he was correct! TBA 
Last year I did start to supplement with eye vitamins just as extra insurance because I no longer eat a head of kale most days, but I most likely don’t need them.
A blurb from AI
A machine that measures lutein and zeaxanthin in the eyes is called a Macular Pigment Optical Density (MPOD) measurement device. These devices, like the Zx Pro and QuantifEye, utilize heterochromatic flicker photometry to assess the density of macular pigment, which is directly related to the levels of lutein and zeaxanthin in the macula. This measurement can help determine an individual’s risk for eye health issues and guide decisions about supplementation
2 Likes
@CronosTempi ‘s post resonated with me. I used to strive to improve my health naturally, until I realized what that really meant for me. Natural for me is dying of heart disease at 47 like my Dad would have if he didn’t have access to modern medicine. No amount of lifestyle changes would have prevented this, only perhaps delayed it by a decade at most. Natural is dying of cancer at 40 like my Mom would have if she didn’t have access to modern medicine. Mid-90’s is about as old as I can find in my family history. Living past that is clearly unnatural. So I took a 180 on my views and have chosen to embrace modern technology to extend both my lifespan and healthspan, and have generally deprioritized lifestyle solutions, taking a similar approach to @CronosTempi. Most of my lifestyle decisions (diet, exercise, etc) revolve around whether or not I actually want to do it, as opposed to some healthspan and/or lifespan benefit.
One area that I slack on is diet - while I’m not SAD, it’s definitely closer to that than your favorite longevity promoting diet. And the primary reason is that I found no difference in how I felt day to day nor in my lab results. As far as I could tell, CGM/bloodwork/trackers/etc, eating 100% healthy was no different from not, for me. For example, looking at my CGM data you couldn’t pick out when I ate 500 calories of white rice or dried mangos or even French fries. And to @CronosTempi ’s point, a large part of this is likely due to taking a GLP-1 and a SGLT2-i. My CGM data only fluctuates by 5-10 points on exercise, otherwise it’s practically impossible to tell where in the day I’ve had a meal.
7 Likes
I’ve noticed the same thing while on Empagliflozin and Metformin. It’s hard to find any glucose spikes and hard to tell when I have eaten compared to the past.
6 Likes
My favorite longevity intervention is currently dapagliflozin which is the only flozin I’ve used.
To @CronosTempi’s point I honestly regret wasting so much time on diet and lifestyle measures alone. It’s still important but couldn’t get me the results I was looking for and eventually I had to get over my fears and face that fact.
8 Likes
I’m using that one too, again. No side effects at all and usually a little weight loss. Empa makes me have to pee all the time, even get up in the night. Had to cross it off.
1 Like
To all the proven and potential interventions should be added our perception of time. According to this article in The Atlantic, our subjective notion that time speeds up as we age, and when we are having fun, has been borne out by experiment. To slow down the passage of time, the article recommends several strategies, including an urge to meditate on death.
I concur. No more blood sugar crashes after a big meal with dapagliflozin. It’s amazing.
The other interventions that really felt beneficial to me (and that I notice if I stop them): telmisartan 80 mg (improved mood on top of blood pressure) and lithium orotate 1 mg (for stress management).
6 Likes
That’s the big one for me as well. I was out of necessity micromanaging my macros to the point that it was interfering with the rest of my life and still having issues. I’m also able to handle salt better which allows for a little more flexibility in eating socially or on the go.
I believe it might have been you that posted a study on PTSD and one of the flozins in rats? Last December a couple months after taking an early retirement I received that diagnosis and within a month of being on dapagliflozin I reached out to an old manager, secured employment and started back to work this week. The bad memories still surface from time to time but I’m able to process and reframe them and move on now instead of struggling.
My nail beds and mucus membranes appear visibly more perfused which has to be a positive change. My only official diagnoses are celiac disease and PTSD and yet dapagliflozin has helped so much that I suspect there was some age related decline happening that just hadn’t manifested into full blown disease. It’s made a huge difference in my quality of life in multiple areas. Even if I don’t live longer from it I’m living much better.
7 Likes
1 Strength training
2 Zone 2 training
3 VO2 max training
4 Sleep
5 Diet
6 Stress reduction
7 Medications/Supplements
8 Social interaction
4 Likes