Lifespan

[Scott 2]

Absent a drug free competition, someone can take whatever they want. More power to them. My only ethical concerns relate to disclosure, which the blueprint guy has done. I do think he buried the lead a little, but he's also obviously selling something. No surprise.


For me personally - I checked my testosterone levels last year. You need to verify both free and total T. The test has to be first thing in the morning. The results can vary a little over time. It's not an exact science. While people will focus on total T, it is the free T number that matters for your lived experience.

I landed slightly below the low end of normal, a little under 300. My GP was unconcerned, especially after a second test put my free numbers slightly above low normal. I insisted on consulting with an endocrinologist. My thought was, I don't want normal, I want optimal! They spent about 30 minutes with me, reviewing my case and questions. They were also unconcerned and advised against any sort of TRT.

Looking more into it - benefits come from burning your candle faster. Increased risk of prostate cancer and heart disease. Possible hair loss. The body also responds by reducing natural production, attempting to restore your pre-TRT levels. So the need to supplement increases over time. You become dependent. It's also possible your body can tie up more of the total T, meaning the free T is slow to improve. The 2nd and 3rd order effects are hard to predict. Hormones are complex.


For me personally, life is pretty good. Before I'd mess with TRT, I'd need to:

1. Have severe problems with motivation, depression, etc.
2. Have exhausted lifestyle variables
3. Have a confirmed near total absence of testosterone

I am re-testing my levels at each annual physical. My lifestyle is a work in progress. I am curious about possible changes.


I don't think it's particularly hard to get TRT. I believe you can game the test and medically qualify through insurance. Factors like sleep, alcohol, exercise, time of test and fatigue cause variations in the number. You can also simply pay an online vendor that specializes in "anti-aging". They're in the business of bumping middle aged men up to max-normal levels. I wouldn't be surprised if some take it further.

I'm sure it's a lot of fun, until the physiological price comes due. I can understand why someone would decide it is worth it.

[white belt]

For the record, I also have no issue with someone taking TRT. Since it requires a doctor’s prescription and at least some medical oversight, the risks are probably much lower than many other performance enhancers people take.

There have been some studies that examine the possibility of using TRT during training and deployments for special operations soldiers because that lifestyle can wreck the endocrine system. As far as I know there isn’t any officially approved program, although on a case by case basis there are likely people using TRT and more hardcore PEDs. I’ve experienced extreme sleep and food deprivation which likely pushed my T into hypogonadism levels for weeks at a time. I wouldn’t recommend living like that. I never got my levels tested after returning back to a normal lifestyle, but based on how I felt I suspect it took months for my system to stabilize again. TRT would’ve likely eased that transition quite a bit. If my life depended on my mental/physical performance in such conditions and I had the option, then I would take TRT in a heartbeat.

In short, with TRT you can raise T levels back into a normal range for someone that has some kind of underlying medical issue. You can also use it to keep T levels normal while someone does just about everything that is known to reduce T levels (high stress, little sleep, disrupted circadian rhythms, low quality diet, etc etc). This is powerful stuff, not like taking a few extra vitamins or eating extra veggies. Long term effects aren’t well researched or understood.

[icefish]

Looking more into it - benefits come from burning your candle faster. Increased risk of prostate cancer and heart disease. Possible hair loss.

Can confirm that last one. I'm on TRT for reasons not related to this thread, and my hair started thinning as soon as I started it. The endocrinologist who put me on testosterone proposed that I stop the balding by starting finasteride. So how does that work? Well, you see, it blocks the effects of testosterone...

There are some very strange medicinal loop-the-loops out there.

[chenda]

Well, you see, it blocks the effects of testosterone...

Finasteride blocks the enzyme 5-alpha reductase which converts testosterone to dihydrotestosterone (DHT), the latter of which causes male pattern baldness in men who are genetically susceptible. It doesn't block hormones, testosterone levels should increase slightly if less is been converted into DHT.

[Ego]

Latest interview with Sinclair
https://news.harvard.edu/gazette/story/ ... been-born/

SINCLAIR: The older idea is that mutations drive aging and, if that’s true, the problem for age reversal is that mutations are very hard to fix. You’d need to repair trillions of them in the body to reverse aging. Instead, we think that it’s mostly due to the loss of epigenetic rather than genetic information, which is great news because we’ve also discovered that there’s a backup copy of the epigenetic information in every cell. So, instead of aging being a hardware problem, similar to having an old computer, we are discovering that it’s a software problem and you can reboot the software of an old computer and make it run like it’s new again.

SINCLAIR: We already have a drug in development to reset the age of the body — it’s in nonhuman primates right now — to cure blindness. We think that the same technology that we use in this paper and in the monkeys could be used to reset the age of literally any part of the body. The applications are as broad as you can imagine — even resetting the brain, which seems to allow mice to learn again. We’re exploring the possibility that when we reset the age of the body, diseases like Alzheimer’s and cardiovascular disease go away. This would be a new way of treating the major diseases of the planet.

[ertyu]

.... sounds a bit like snake oil, not gonna lie. no need to bust your ass exercising, have that steak, too, and then when the time comes we'll just "rest the software" no worries

[Slevin]

That sounds pretty cool, but agree with @ertyu, having a result in mice and sounding certain about the outcome in human trials eventually becoming a medicine with a more-than-modest effect is pretty ridiculous. It is basically a moonshot at this point, and this guy is claiming it’s totally going to stop aging because it is bioplausible.

It would be really cool if it works, but I’m not holding my breath until we see human results in RCTs. https://m.youtube.com/watch?v=NmJsCaQTXiE&t=817 , as explained here, this is the “starting point” of telling whether a drug will do something in humans, and it’s irresponsible of the doctor to be claiming large scale human effects after the scale of trials that they have. I think it’s viable to call him a snake oil salesman at this point (now to be fair, he may totally understand all this, but needs more funding, so has to make outrageous claims to the public to secure it or something).

Does that mean it’ll work? No. But if it works to cure blindness in a monkey, I am optimistic it’ll work in a patient. And if we’re not successful in the next few years, somebody will be, because there has been about $5 billion invested in aging drug development just since our Nature paper came out in 2020. There are many companies now working on this. So, while we’re at the forefront, there are many others who should succeed if we’re not successful first.

Yes, things will inevitably always be solved because you throw a lot of money at them. That’s how we solved cancer and heart disease so quickly too /s.

[Scott 2]

I finished Levine's True Age book. In short - she wants you to test biological age every 6 months to a year, using the data to evaluate impact of your health interventions. She consulted on a saliva based test for the same. Cost is $300 per test, if you subscribe.

She developed an older test, using values from your labs. A spreadsheet attempt to implement it is here:

https://www.oliverzolman.com/phenoage-calculator

I had most of the data, took average values for the missing ones. It put me about 10 years below my chronological age. My initial interest was tempered by the realization there's nothing particularly actionable about the number. At the end of the day, you're still acting upon deviations in individual tests.

Theoretically the saliva test could provide your aging type, focusing intervention on your areas of highest risk. But again, I have to wonder, why not focus on your blood tests with poor results? Since changes tend to be synergistic and lifestyle constrained, I'm not that excited about my aging type. I'm already doing what I can.


Her general recommendations are typical of the longevity folks. Eat less. Limit animal protein. Fast. Exercise. Maybe some drugs, but the data is still out. In her mid 30's, she isn't taking anything. She was negative on holding a lot of muscle mass. She likes short sprints of ketosis (like a week), but doesn't like it as a chronic lifestyle choice.

Areas where she might change my perspective:

1. I take 50g per day of whey protein isolate. She favors low protein. At some point, I may reconsider this choice.
2. She is cool with stress, approached with the attitude of "this will make me stronger". I like to permanently remove a stressor, but might be coming around.
3. She sees positives to a few 5 day fasts per year, putting the body into ketosis. Not currently compatible with my training goals, but maybe something to try eventually. Her fasts tend to be very low calorie, rather than water only.

[mathiverse]

I think it's interesting that the Blueprint guy decided that taking 100s of supplements and eating only smoothies and pudding was better than figuring out how to have a diet of regular food with minimized supplements. Maybe because supplements and simple foods (the smoothie and the pudding) have more precise contents? (Eg my pill has 500 mcg of vitamin D)

[IlliniDave]

I've gotten intrigued with this topic as the M.O. I'm following to correct metabolic syndrome and related things has some roots in the study of the Blue Zones and emphasis on mitochondrial health and restoration. People who get into their 90s and even over 100 in good health all tend to display very robust mitochondria where the typical Western Dieter has mitochondria on life support often prior to their 70s. Also reduced calories and IF are inherent to the regimen. I'm not deep diving into that offshoot yet since I've got pressing short-term needs.

[Scott 2]

has some roots in the study of the Blue Zones

Have you looked into claims the Blue Zones are based on bad data?

https://www.biorxiv.org/content/10.1101/704080v1.full

I also see articles that say they are good data:

https://academic.oup.com/biomedgerontol ... ogin=false

It's hard to know what to trust.

[OutOfTheBlue]

For what it is worth as as a single point, one of my two grandmothers is from a blue zone (Ikaria, Greece) and still alive, having been born in July 1911.

[IlliniDave]

Have you looked into claims the Blue Zones are based on bad data? ...

It's hard to know what to trust.

Yep, it hard to know who to trust. But even if all those people lied and were really 95 or even 85 and still walking their goats up the mountain every day; relatively speaking, it's a distinction without a difference. I'm on course to fall well short of what the actuarial tables spell out for me. The only good news for me is that there was quite a lot of longevity on my maternal grandmother's side (although not her, she only made it to 81). But that's the branch from which my mitochondria come, so if I pamper them I might get lucky and make it to 78 which is when I'm scheduled to die, and make it there with a minimum prelude of morbidity.

[7Wannabe5]

My maternal biological grandfather was 5'5" and 240 lbs in 1940 at age 40, and then lived another 43 years in relatively good health. His mother lived into her late 90s. My mother seems to be on same/better track as a very overweight human with no problems related to metabolic disorder at age 83 (she does have other problems.) My third sister, who has been relatively chubby since birth, but also consistently engaged in sports, had genetic analysis done, and discovered she has pretty much all the genes that tend towards making a human "naturally" or "inherently" chubby/overweight. In the U.S., the broadly defined group that lives the longest is Hispanic Females who are moderately overweight. OTOH, there are some groups that are inclined towards metabolic disorder at lower BMIs; in the U.S this would be African-American Males. In general, although opinion on aesthetics may greatly vary , the hormonal profile that will give you tendency to carry weight on your ass offers somewhat more lifespan than it negates.

[chenda]

Chubbyness also helps infill fine lines and wrinkles. I've seen lots of people loose weight and simultaneously visibly age.

[7Wannabe5]

@chenda:

Yes, as they say "Fat don't crack." Of course, there are also aesthetic procedures one can purchase/undergo that provide same effect without the risks associated with excess weight. Another potential problem that some men might want to take into consideration is that they can diet themselves out of range of their dating/mating market. Most females sub-consciously prefer men who are 10% larger than them along some trajectory. However, this can certainly be compensated for by knowing how to inhabit space with stance or demeanor.

[mathiverse]

... one of my two grandmothers... born in July 1911.

OMG! Wow! She is almost old enough to be in the verified top 100 oldest women on Wikipedia. Two or three more years!

[IlliniDave]

... the hormonal profile that will give you tendency to carry weight on your ass offers somewhat more lifespan than it negates.

Unfortunately our mitochondria only come down through our mother, from her mother, from her mother's mother, etc. I have some longevity scattered around in other quadrants which might help a little, but likely aren't the drivers for me. I think Asians in the US top Hispanics in the US for longevity, but that's a quibble.

You are correct in the sense all fat is not created equal. Subcutaneous fat is undesirable for some due to appearance concerns, but it is metabolically neutral, and something like 20% of obese people in the US have perfectly healthy metabolism and tend to live a normal healthy lifespan. It's visceral fat (think beer gut/belly fat) packed around organs that is both harmful in-and-of itself (it is not metabolically neutral), and symptomatic of serious underlying problems. Even worse is intracellular fat which gets dumped in the liver and other places where it shouldn't when things have really gone awry. Both of those are nutrition-driven with the caveat that specific optimal nutrition needs are not the same from one individual to another.

So having a big butt, thunder thighs and fleshy arms aren't really indicative of chronic metabolic problems on their own. But someone relatively thin/normal except for a burgeoning gut is probably in bad shape (i.e., like me). I don't know if the tendency to more readily accumulate subcutaneous fat speaks to longevity itself (now that we don't face severe famines very often) but it does probably indicate more resilience to the SAD diet and lifestyle assuming it's not accompanied by excess visceral fat.

[7Wannabe5]

@IlliniDave:

Yeah, I'm definitely more in the big butt category, although the belly is also getting worse post-menopause and multiple rounds of prednisone last year. Probably, I have about 30 years more years of figuring out how to keep myself entertained. I think that one of the reasons why men die younger might be that they often lose the will to live once they can no longer function well sexually. So, that thought provides me with a little bit of my purpose and entertainment in these my golden years. However, not even as "lucrative" of a purpose as tutoring math to the disadvantaged children, so I'm trying to limit it to 10 hours/week max. which I think is also approximately the time budget for such activities suggested by the Wall Street Players.

[IlliniDave]

7Wb5, you've perhaps hit on another good reason for men to eschew statins.