Can you share your Longevity / HealthSpan Regime?

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#104

I would like your thoughts on time-restricted feeding
As a child, I never wanted to eat breakfast and couldn’t figure out why everyone was force-feeding me. As I grew up I adopted the social norm of having breakfast. After I retired I needed to lose some weight, so along with exercise, I did a keto diet until I reached my own goal of 175 lbs. Then I just did time-restricted feeding. I do ~ 18/6, not because I have a strong belief that it is optimal, I just don’t feel hungry before 1 PM. My first meal is at noon because that is convenient for me. The plan is working so far and I eat a somewhat South Beach Diet, again by natural choice and not by plan. I do not count calories and I eat until I am full.

So, do you think I should force myself to eat earlier in the day as some proponents of time-restricted feeding advocate?

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#105

I don’t eat too late (last meal >3 hrs before bed) because there is suggestive evidence of “fasting while sleeping” on glymphatic processes that may offset or delay dementia (fun fact - Alzheimer’s used to be my white whale).

It also consistently affects my sleep (actigraphy & subjective feelings), so I almost never do that anyways.

I’m shooting in the dark with timing and IF in the first place - it’s weak evidence in human trials compared to say traditional Mediterranean diet (see Cochrane review) and it’s speculative. I first got the general idea from traditional Okinawans eating more earlier in the day and little towards the end (or skipping dinner) - before IF went sort of more mainstream and they seem to have better sleep. My IF 16/8 probably does not result in significant weight loss, all else equal.

I’m assuming getting to a fasted sleep state quicker is generally better. It takes ~6 hrs to digest your food but there are ways to transition slightly quicker that I do personally - i.e. light dog walks after last meal, less fat in last meal. (I don’t do intense exercise right after eating or taking things like metformin - it’s too sharp of a transition)

I occasionally shift a bit to 11am-7pm in terms of occasional (~2-3x a month) social functions where eating is involved, but otherwise consistent timing.

One of the reasons why I refrain from taking things like metformin, berberine, and/or acarbose all the time is I worry about hypoglycemic responses which can depend a lot on individuals and I don’t like relying on subjective feelings based on my experience of talking with diabetic patients who ended up with a CGM.

Review of the proposed mechanisms (I suggest reading it entirely and going through all the references):

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#106

Thank you for taking the time to share your experience.

Both the keto diet and time-restricted feeding raise my morning blood glucose levels while lowering my HEMOGLOBIN A1c levels.
Do you think perhaps A1c level may be a better marker than fasting glucose level for those on keto or time-restricted eating protocols?

#107

I personally use a CGM with relatively high accuracy as my primary data source for glucose changes and computation of autocorrelation functions (there are some issues, but minimized). I do take HbA1c regularly for reference and fasting glucose comes with the lab bundle.

In diabetes screening, HbA1c and fpg are both used. Fpg is not great because stress can easily throw that out of whack, so I wouldn’t rely on that over 2 hr oral glucose test.

There are pitfalls with HbA1c in various clinical scenarios (ie in my case, when I donate blood it is falsely lowered) but it’s a better index of averaged glycemic exposure since RBC live for ~120d.

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#108

@desertshores - Charles, this is simplistic, but Dr. Fung does a good job in breaking down the studies of fasting and time restricted eating. He has benefited from the popularized fad component, but I still think has some basic values that apply. Also, Dr Longo out of USC longevity center, does a nice job of breaking down many of the studies on fasting and time restricted eating with most interesting being benefits of cancer prevention and fasting before chemo treatments to enhance normal cell protection from chemo and higher sensitivity of cancer cells to chemo. He is the inventor of the Prolon diet or fasting mimicking diet that promotes benefits of fasting without the loss in muscle mass.

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#109

I think this belongs here:

#110

I like Dr. Attia’s approach. I still think Dr. Tong @tongMD is ahead of the curve with his software algorithm approach.

I start with risk of do nothing vs. risk of therapeutic option. Next step, is there a subjective change to warrant the risk of taking the therapy? - For example in hormone replacement, is there an improvement or resolution of hot flashes, night sweats, libido and mood. If there is not, then probably not worth any risk, if there is then weigh it out for the individual. Is there objective metrics that has data to support the a change a lab or measurement that is supportive of continuing treatment. Example might be a change in vitamin D level, improvement in A!c level or even cholesterol that support the use of the therapy even if no subjective improvement. Lastly, even though no subjective or objective changes or measurements, the risk vs. benefit for the individual is worth taking the therapy - a 20+ year old taking Rapamycin despite no subjective or objective improvements.

Thanks for sharing this!

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#111

Related to this Attia referenced post, some thoughts:

  • Matt (MK) responds, “I think it depends on the biomarker you’re talking about.”

  • If you’re talking about a biomarker of efficacy for aging, he agrees that we don’t have that for anything because we don’t have any biomarkers of efficacy for aging (MAC: aging clocks? but hotly debated. We have ever deeper and more powerful GWAS of longevity cohorts teasing out longevity genes/pathways, how to translate to a biomarker?)

  • But we do have clear biochemical biomarkers, certainly for rapamycin (MAC: true)

  • We know rapamycin is a very specific inhibitor of mTOR, and we have good biochemical ways to measure mTOR inhibition (MAC: yes in mice after we kill them, humans not so)

  • The challenge is we don’t know what level of mTOR inhibition is optimal for aging, and that gets back to the aging biomarkers (MAC: not true, we know VERY WELL in mice the level of mTOR in various tissues associated with aging, thoroughly documented after we euthanize them. We don’t know the human translation; so he likely was talking about humans)

#112

I’ll add in this study, that BCAAs which are well known for mTOR activation, yielded an average longer lifespan in middle-aged mice (sort of the opposite of what one would expect if it was only about mTOR inhibition), partly from SIRT1

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(10)00304-9

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#113

More average survival (9%) than lifespan (4.5%)…not at all close to rapamycin longevity efficacy in the WT mice (see red box below) mTOR is still king.

So does eating enriched BCAA improve healthspan, but as expected, not increase lifespan…at least, not curtail it? mTOR absolutists would say no, BCAA bad.

Although there are many more studies showing increased BCAA indeed reduces lifespan.

What if they did BCAA supplementation AND Rapamycin together?

Wait did you mention SIRT1…buried for dead? Sinclair is smiling.

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#114

@MAC @tongMD I really like this discussion!

A healthy 25 y/o has peak levels of IGF-1 and testosterone. Most have do not have signs of age related disease or symptoms of age related high mTOR stimulation.

Now take the same person and move them to 50 y/o. IGF-1 and testosterone levels are lower - mTOR seems to get stuck in constant “overdrive” and by inhibiting it with CR, Metformin and Rapamycin, we see a reversal of signs and symptoms of aging and longevity. However, if you take the same 50 y/o and just replace the testosterone and IGF-1, at least anecdotally in many patient populations, you see a reversal of many symptoms of aging and many claim feeling more youthful.

My point is that there must be much more going on than a simple on and off mTOR signaling. What is the difference from young people mTOR vs. older mTOR and can we use this model to better control aging? Is it just that old cells ( shorter telomeres ) respond differently? Many people on this site do both - stimulate mTOR with exercise, higher protein diets, testosterone replacement, peptides to enhance iGF-1 / GH and at the same time do pulsed Rapa, take Metformin, practice CR and fasting. Is this just a battle of Healthspan vs. Longevity? If we had the experts in the Rapa / mTOR field - that would be the question I think is the most interesting.

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#115

Almost all growth factors increase cellular proliferation and lead to a short term youthening effect. We’ve seen this with growth hormone, androgens, and vascular endothelial growth factor. Many times up regulation of telomerase is part of the equation as well.

Over the long haul the effects are pro aging due to hyper function, senescence, telomere shortening, etc.

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#116

Sure! All good points. So why does up regulation of mTOR from aging not cause a youthful effect. Why does high levels of growth factors not seem to be as harmful to people when they are younger? A few of the forum members that take TRT, say they understand it may not help with longevity or even shorten it, but feel the QOL is worth it. I like the Telemorase point since it could be the duration of exposure that is what is important - old cells vs. young cells.

Thanks for your points!

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#117

Yep. This.

Hormone replacement is highly tricky since the endocrine system is tightly controlled and hormones can have different signals in different places.

Part of the reason why I don’t currently use hormonal supplements like melatonin directly (melatonin is not just for sleep, it controls other things ie puberty, dopamine) in absence of a clear deficiency. It’s safer to control the signals to influence melatonin production and inhibition aka blue light and avoidance of blue light at the right times.

As we know, Testosterone is a signal to the body to build muscle, grow, and reproduce (libido). For HGH, GH directly hits IGF-1 as a major regulator of the aging process.

When I think of both - I think of bodybuilders using anabolic steroids (hGH injections & testosterone) and acne. High levels of IGF-1 and testosterone are associated with acne - which I associate with a disease of “Westernization”. Okinawans pre-world war II had zero incidence of acne, verified by US physicians, yet these centenarians have closer to younger levels of testosterone and clearly decent libido as per their reported sex lives. They also had higher IGF-1 bioavailability and improved insulin action. Seems there is not much reason to do “replacement therapy” in those cases.

Resistance training is the easiest way to tell your body to go to more optimal levels of testosterone and feel great. Eating >3 hrs before bedtime and sleeping well is the easiest way to more optimal levels of growth hormone as deep sleep and REM sleep are the most important. Avoiding opioids and endocrine-disrupting chemicals are some of the big ones.

Taking enough Vitamin D3 (note Vitamin D is a hormone - I only supplement 1000 IU due to lack of UV exposure and diet to avoid a deficiency), enough zinc (diet), and enough magnesium (I use supplement to increase amounts crossing the blood-brain barrier at night before sleep and avoid any possibility of a deficiency - not much evidence though - it just appears to work for me).

Anything that involves a high turnover of cells can make the risks of cancer worse. In mice, we have a clear picture of GH which can be pro-aging (see Ames dwarf mice). In dogs, smaller breeds live longer than larger ones.

One of the risks of being a tall guy is cancer. Same with bigger dogs and larger mice. In humans, I suspect the longevity relationship is muddied IMO because of socioeconomic factors and mate selection.

https://www.nature.com/articles/35106646

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#118

I met guy (Cameron Sepah) was in a Digital Health incubator I was in a number of years ago with a different startup company… but he’s gone off on his own now and has started a company that is focused on increasing mens testosterone via other methods than straight testosterone injections… I have not looked into it much, but he seems to be having some success (with the business at least, not sure how his customers are doing).

Does anyone here have an opinion on this approach that he is using?

Maximus is built to support men in their quest for testosterone optimization, and one major tool they use is a prescription of enclomiphene alongside blood testing, adjunct supplements, and community support.

https://profiles.ucsf.edu/cameron.sepah

https://pro.endocrineweb.com/endoscan/201604/abstract/enclomiphene-citrate-improves-hormone-levels-while-preserving-

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#119

We don’t talk much about little known boron but it’s an excellent regulator of sex hormones along with cancer prevention and significant anti inflammatory effects.

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#120

Yep, I have looked at Tongkat ali, boron, and other things too. Going to wait it out for now personally

#121

Low insulin replaced in DM is easy. Levothyroxine / Armour Thyroid to replace hypothyroid is easy. HRT to replace low levels for symptoms of aging is somewhat acceptable, but many if not most argue that risk is not worth the benefit. Hormones to enhance what is considered normal becomes even another layer of controversy. Acne would be a sign of too high of a level - body builders are trying to enhance beyond scope of what can be achieved “normally” Body builders will also use insulin to maximize muscle gain.

Easiest to start with SLEEP - DIET - EXERCISE - SPIRITUAL since lower risk. Rapamycin is in the realm of risk of unknown results vs. risk on known results.

I am fascinated with Okinawan Diet. Before enhancement options, they were outliving everyone.

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#122

In younger men that have ability to produce their own testosterone, clomiphene and occasionally HCG can help increase testosterone levels. It would make sense that this would also work, but if the testicles have lost the ability to make testosterone then replacement with testosterone would make more sense. The dose of testosterone patch in the study would be consider suboptimal is some circles of replacement.

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#123

FWIW

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