Thanks. I thought the main issue was the body’s growing failure to clear senescent cells which then accumulate. Which of these “causes” are involved in reducing clearance vs causing senescence?
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The “natural” removal of senescent cells is as varied as the sources.
The key process is the immune system. Anything that impairs the immune system will prevent that particular system from doing the job (among the many it does) of clearing senescent cells. It seems to take a fairly robust immune system as many of the SASP components are there to “hide” the senescent cells from the immune system.
This type of “hiding” is common in bacterial and viral infections as bacteria and virus modify the immune system to be more “friendly” to the infection. For example Covid make significant modifications to the immune system to enable it’s on going infection and proliferation Staph modifies the immune system, etc.
This is one of the reasons I’m so interested in the TRIIM and TRIIM-X studies and why I’ve adapted it to my current program.
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JKPrime
#24
Assuming for a moment that lab mice age in phases too and aging is non-linear, it may explain why some highly touted anti-aging interventions failed to extend max lifespan much. It also may explain why with certain drugs like Rapa nearly all the anti-aging benefits can be obtained when started late in life in between mid-fifties to sixty.
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cl-user
#25
The paper is interesting.
BTW here is the ITP circus 
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ng0rge
#26
Nice! That’s Rich alright, with a cardboard moustache. And I think I see @RapAdmin in the front row. They’ve still got the mice on some kind of drugs.
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ng0rge
#27
New article on this from Scientific American.
https://www.scientificamerican.com/article/drastic-molecular-shifts-in-peoples-40s-and-60s-might-explain-age-related/
The reasons why the ages of 44 and 60 might be turning points in health are not yet apparent, but the study authors hope to probe several hypotheses in future work. Snyder suspects that for people in their 60s, declines in immune system function might precipitate a more widespread breakdown of organs. A midlife decline in physical activity, meanwhile, could explain the differences seen among participants in their 40s.
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Did the study report how they measured metabolism? The curve shape is not consistent with the research from Pontzer
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My guess is that something breaks at these two points and your body changes to compensate. An Example is a lack of certain amino acids resulting in more ROS. And then this shuts down other processes or severely impairs them.
Your body is wonderful at adapting to changes, but sometimes I wish we had a better dashboard to know when a problem is approaching. Something like a ‘Change Oil’ light for health.
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I liked reading the Exercise Paradox.
When I was overweight… okay obese… I first cut calories significantly 60 percent… drank only water and walked 3 miles a day.
After losing about 30 plus pounds of fat. I was pretty scrawny… it was then I started hitting the gym and weight lifting. Muscles slowly grew… could eat as much as I wanted… no weight gain.
Makes sense why it worked for me.
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What was the timing of TRT in this timeline? Did you experience body recomposition from TRT alone or did it require weight lifting (or other)?
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Loss the weight at age 55 years. I lifted for about 5 years (age 56 to 61 years) was toned but not strong.
Started TRT at age 61 years so been on TRT 6 years at 200 mg 1 ml injection weekly with 1 mg anastrozole. Now filled physically and stronger. I think the TRT alone was helping keep fat down and build strength. In combination with rapamycin - has shredded to very toned and strong.
Over weight age 55 years - lost 30 pounds plus.
Age 56 years After 30 pound weight loss ready to start muscle building.
Age 60 years after working out about 5-years - no TRT… no rapamycin.
Age 62 years on TRT 2 years and rapamycin 1 year combo
Currently age 67 years - this week 2025
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Yep. That’s the power of TRT. Certainly enhances the quality of life. But, the longevity, perhaps not. As a body builder for many years, I admire the effort it takes to achieve the sculpted look one desires. Robby Robinson at 78:
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Ahhh… but the rapamycin combo with TRT- it might beat the odds… and give longevity. Each balancing the other’s weakness.
Currently at 67 years and no heart calcium/plaque… no chronic inflammation… no osteopenia - strength and health.
Robby Robinson at 78 looks good - I hope my skin quality will be better at that age thanks to rapamycin.
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You wrote: As a body builder for many years…
Are you on TRT now?
What is your physiological condition currently… average… toned… muscled?
Assuming you are on rapamycin… yes?
Benefits?
Not on TRT now, haven’t been since 2021. TRT elevated my iron levels and lipids (so does rapa but to a lesser extent). I have the genetic variants that contribute to higher iron (compound heterozygous H63D/C282Y). But, the expression confounds the hematologist because I have low ferritin. I would say I’m average now, more like a cyclist than body builder. I still get complements when shirt off, muscle definition still visible. My natural state is thin, so, the only way I could gain weight and bulk was to eat like a pig (healthy food-high amounts) and work out like a fiend. Goal accomplished age 20-50, but couldn’t keep that up due to family and building a business. No time to spend 2 hours in the gym 5 days a week! Beyond that, still do calisthenics daily. At my peak was 187, now 158. Not on Rapa now since about a year. Although I’m likely going to start again. Also, considering TRT again because it’s becoming difficult to maintain level of exercise and the oral route seems interesting now that Kyzatrex is out. The impact of aging for me, strength wise and other factors didn’t really become noticeable for me until about age 68, creeping in. Now at 74 it’s more dramatic. As we all know here, aging is not linear.
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