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Anti aging thread


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#41
Singularity Kills

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David Sinclair talks here (briefly) about the cellular round trip technology George Church is working on which involves pulsing the body by telling all cells to go from to stem cell and back again. He obviously doesn't want to give numbers and data but you can hear the excitement in his voice.

 

https://www.youtube....h?v=bF5yl9OGKzw


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#42
starspawn0

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Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming

https://www.biorxiv....0.1101/710210v1

George Church and David Sinclair are both coauthors on this paper, which has like 26 coauthors.
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#43
starspawn0

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Yet more protective and anti-aging effects of Metformin... in rodents, and possibly also in humans. The human trials have not been performed, but the evidence probably exists in large-scale patient records.

https://www.mdpi.com/1422-0067/20/1/42

Despite growing evidence on metformin as a candidate drug for renal diseases, in-depth research is imperative to unravel the molecular signaling pathways responsible for metformin’s renoprotective actions. This review will discuss the current state-of-the-art literature on clinical and preclinical data, and put forward potential cellular mechanisms and molecular pathways by which metformin ameliorates AKI/CKD.


And could delay or remove the need for dialysis.

I saw another study showing that it could also protect the liver.

Alas, that drug is off-limits to you unless you have diabetes or pre-diabetes. If you are healthy... get to the back of the line. I think that's fundamentally unfair, especially given the drug's well-established safety. In fact, it's probably safer than most over-the-counter drugs.

I think we need leadership in Washington that isn't afraid to revise the role of the FDA, allowing people to try well-established, safe drugs for off-label uses.
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#44
starspawn0

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This is an interesting article from December of last year:

E-bandage generates electricity, speeds wound healing in rats

https://www.scienced...81219115519.htm

It's known that Electrical Stimulation Therapy (EST) speeds the healing process of wounds in animals and in humans; however, I was surprised how effective this new bandage was for rats:
 

Wounds covered by e-bandages closed within 3 days, compared with 12 days for a control bandage with no electric field. The researchers attribute the faster wound healing to enhanced fibroblast migration, proliferation and differentiation induced by the electric field.


Amazing!

There's also evidence that EST can:

* Reduce pain near the surface of the skin at different areas of the body;

* Induce the regeneration of peripherial nerves. Yes, it really does work, according to multiple studies!

* And, at least in rats, it has been shown to massively boost androgen receptors. This should be of interest to body builders, or people low in androgen receptors.

It's possible there are yet more uses that haven't been tested for yet. For example, EST inside the body might actually rejuvenate major organs. Nobody has done that experiment, as far as I know.
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#45
Jessica

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Scientists reverse aging process in rat brain stem cells

by University of Cambridge

New research, published today in Nature, reveals how increasing brain stiffness as we age causes brain stem cell dysfunction, and demonstrates new ways to reverse older stem cells to a younger, healthier state.

 

The results have far reaching implications for how we understand the ageing process, and how we might develop much-needed treatments for age-related brain diseases.

As our bodies age, muscles and joints can become stiff, making everyday movements more difficult. This study shows the same is true in our brains, and that age-related brain stiffening has a significant impact on the function of brain stem cells.

A multi-disciplinary research team, based at the Wellcome-MRC Cambridge Stem Cell Institute (University of Cambridge), studied young and old rat brains to understand the impact of age-related brain stiffening on the function of oligodendrocyte progenitor cells (OPCs).

 

https://medicalxpres...-rat-brain.html



#46
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The Transhumanists Who Want to Live Forever

https://www.technolo...s-live-forever/
 

Given these clues, Clement is expanding his medicine cabinet of pills. So far he has financed and supervised four small studies, in volunteers, of treatments found to extend the healthy lives of rodents—the immune drug rapamycin, the supplement NAD+, a combination of compounds that kill off aged cells, and injections of plasma concentrated from umbilical cords. His aim is “to do as many small trials as possible” to generate and publish basic information on safety and possible benefits. With that, he says, people interested in life extension “can decide to take the risk.”


Good for him. I should probably read more what this guy is up to.

As I said before, we need to revise the role of the FDA, so that people can experiment with drugs that are now considered off-limits (unless you are unhealthy).
 

“I think anybody under 50 who does not have a genetic liability will make it to longevity escape velocity.”


That's good to hear -- though, I might have some "genetic liabilities". Based on lab test results, I am in perfect health; probably the top 10 percentile, healthwise, and maybe even top 2 percentile. I don't have high blood pressure, diabetes, or heart disease; and various tests I took indicate that my risk of development any of them is pretty low.

One thing mentioned:
 

After Kirkland showed that another drug, called fisetin, makes mice fed it live about 20% longer, self-experimenters didn’t delay in trying it. “The Mayo clinic protocol called for 180mg, but I decided to [hit] those zombie cells harder,” read a post I found on the Age Reversal Network, a bulletin board that’s a hotbed of longevity tips.


I looked into fisetin. Unfortunately, it's hard to get a lot of it in supplement form -- and you need a lot of it, because it has low bioavailability. One solution would be to find a better way to extract it or produce it; another would be to find some way to enhance the bioavailability (e.g. via injection or patch).


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#47
starspawn0

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This is a fascinating new non-invasive cosmetic surgical technology, that could make most types of plastic surgery look barbaric and primitive:

https://www.recrosme...in-development/

Basically, the device sucks out little columns of skin and other tissues, which close within just a few minutes, and cause the skin to pull together tighter. Clinical trials (with this or similar tech) have been conducted on adults over 64 years old, and it has shown remarkable ability to tighten skin without scarring -- and should work basically anywhere on the body. This could a way to keep people looking young well into their 70s or 80s. Got wrinkles or skin laxity? Just remove 5% to 10% of the skin by surface area, without scars, and the problem is solved! It also has been shown to remove small tattoos without scars, almost like having an eraser tool like on a paint program (software).

I found out about this device by basically guessing something like it should work, and thought about writing a post about my idea. An internet search or two later, and I discovered it was an experimental technology!


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#48
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What's My Best Chance of Living Forever?

 

https://gizmodo.com/...ever-1837736848



#49
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Brain, Liver and Muscle Rejuvenated by Calibrating Aged Blood

https://www.leafscie...ing-aged-blood/

We hypothesize that altered intensities of a few morphogenic pathways account for most/all the phenotypes of aging.



If true, then it might be relatively simple to turn back the clock, and make people look and feel younger.
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#50
starspawn0

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David Sinclar has a new book out, and did a podcast interview with Peter Attia. It's very fascinating:

https://peterattiamd...davidsinclair2/

He talks a lot of "methylation clocks". Basically, by looking at the DNA in your cells, they look to see where it is methylated (a carbon tacked-on), and based on that pattern, they can tell how old you are. Furthermore, they found that smoking causes the "clock" to tick faster -- and they can even estimate how many packs you have smoked per year on average, just based on the methylation clock.

Metformin, fasting, and NAD-boosters can slow the clock down, but not reverse it. He and his lab are working on ways to reverse it.

One problem, he says, is: how do the cells know what the original methy pattern was to revert back to? He says that new evidence is showing that, somehow, cells know what the youthful state of the DNA should be. As I recall, he says nobody would have believed it years ago; but the evidence is coming in that they do.

He also talks about his work on reversing aging in the eyes of mice.

Breakthroughs are coming along at a rapid rate!
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#51
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Sinclair was also on Rogan's show today, and mentions that study with 9 people who had their age reversed 2.5 years:

YouTube
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#52
Erowind

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.

 

How long and often does a person need to fast in order to potentially gain anti-aging benefits from it? 



#53
Zaphod

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.

 

How long and often does a person need to fast in order to potentially gain anti-aging benefits from it? 

 

 

I don't think there is a good answer on that unfortunately - studies focusing on different fasting regimes and comparing them haven't really been done, at least not rigorously (I remember Peter Attia saying he wished they had).

 

A lot of people have suggested you need 3-4 days to get to autophagy and to experience the real benefits, so I've been doing Thursday to Sunday fasts once every 3 months. As well as intermittent fasting (16-20 hours) every day. I'm sure there may be a better strategy, but I don't find this schedule difficult at least. 


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#54
starspawn0

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I did a week-long fast (9 days, as I recall) a little over 10 years ago now. It's difficult to pull off.

There is some recent research on early intermittent fasting:

https://www.ncbi.nlm...les/PMC6627766/

Time-restricted feeding (TRF) is a form of intermittent fasting that involves having a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic health in rodents and humans. Here, we performed the first study to determine how TRF affects gene expression, circulating hormones, and diurnal patterns in cardiometabolic risk factors in humans. Eleven overweight adults participated in a 4-day randomized crossover study where they ate between 8 am and 2 pm (early TRF (eTRF)) and between 8 am and 8 pm (control schedule). Participants underwent continuous glucose monitoring, and blood was drawn to assess cardiometabolic risk factors, hormones, and gene expression in whole blood cells. Relative to the control schedule, eTRF decreased mean 24-hour glucose levels by 4 ± 1 mg/dl (p = 0.0003) and glycemic excursions by 12 ± 3 mg/dl (p = 0.001). In the morning before breakfast, eTRF increased ketones, cholesterol, and the expression of the stress response and aging gene SIRT1 and the autophagy gene LC3A (all p < 0.04), while in the evening, it tended to increase brain-derived neurotropic factor (BNDF; p = 0.10) and also increased the expression of MTOR (p = 0.007), a major nutrient-sensing protein that regulates cell growth. eTRF also altered the diurnal patterns in cortisol and the expression of several circadian clock genes (p < 0.05). eTRF improves 24-hour glucose levels, alters lipid metabolism and circadian clock gene expression, and may also increase autophagy and have anti-aging effects in humans.


But the study is too small, as are most intermittent fasting studies.

This is close to the time window that I eat in. I typically eat from about 9 am to 3 pm (or slightly later than 3). I might try to move it back to 8 and 2, if I can manage it.
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#55
Erowind

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@Zaphod and Starspawn

Did either of you eat at all during your longer fasts? I know some people eat 500-600 calories a day and consider that fasting. Would that work or does a fast need to be complete starvation?

#56
Zaphod

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I have found the second day of fasting to be by far the hardest in terms of hunger, by the late third and fourth day I am no longer hungry at all really. I will try a 7 day fast at some point I think.

 

I don't really like breakfasts so my eating window is 2pm-8pm usually.

 

@Erowind - I did not, just had water, tea and a bit of salt. I'm not sure if having a small amount of calories is as effective as 0 calories, but personally I find it much harder to only eat a little than nothing at all. There is something about having some food digesting that propels me to be even more hungry than if I had eaten nothing.



#57
starspawn0

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On the longer fast 10+ years ago, I didn't eat anything at all for the first couple days, just drank water; and then towards the end of the week, I had some soup (which is low-calorie, anyways). Definitely the calorie intake towards the end was under 500 per day, and probably under 200.

#58
starspawn0

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Josh Mitteldorf

https://joshmitteldo...something-else/

This part sounds important:
 

For most of the clocks, the big drop in epigenetic age came during the last three months of the trial (months 9 to 12), raising the possibility that there is a latency period, and a longer trial might produce a bigger drop in epigenetic age.


Furthermore, the improvements to the methylation clocks did not bounce several months after the trial. It looks like the changes are permanent.

Who knows what the limit is?... Maybe 10 years or more of de-aging are possible.

....

Oh... one more thing, in case you missed it: one of the authors on this study is the go-to guy for methylation clock analysis -- he has the most accurate one, and is a major player in the field:
 

This level of success might have led to a modestly encouraging publication, but fortuitously, Fahy made contact with Horvath toward the end of the study, and Horvath volunteered to analyze changes in the subjects’ methylation. (TRIIM had preserved some blood samples from each of the patients at each time point, so this could be done retrospectively.) The result demonstrated a decrease in methylation age, consistent enough to be visible in a sample of only 9 subjects. This was the first time that a treatment in humans led to a setback of the epigenetic clock.


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#59
starspawn0

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This is a neat post about fasting and autophagy:

https://www.thecut.c...-autophagy.html

And the fasts have to be for 24 hours or longer?

It’s not clear. The 24-hour marker was pulled from mice studies, and mouse metabolism doesn’t necessarily correspond to human metabolism.

In an interview with the Cut, nephrologist (kidney doctor) and fasting researcher Jason Fung suggested that autophagy, in which “your body will take the oldest, junkiest proteins and burn them for energy,” happens “probably in the later stages of a long fast — somewhere around 20 to 24 hours, is my guess, and it probably maxes out somewhere around 32 hours, again is my best guess.”


That echos what Zaphod wrote earlier.

I think I might try a 32 hour fast. I might postpone eating until tomorrow night, after my afternoon meal today, to try it out.
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#60
starspawn0

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I just finished a 42-hour fast. I would have pushed it to 48 hours, but it would have required rescheduling my meals for today. Basically, I fasted from 3 pm on Friday to 9 am Sunday.

I didn't get hungry at all. No sleep disturbances, either. However, I've heard that if you prolong it for one more night, you start to experience sleep problems, racing pulse, and other things. I would have tried it longer, but was afraid it would impact my work tomorrow (and also get my diet body clock out of whack).

But, yeah, it was so easy to do that it wouldn't have taken any more willpower to go one more day. I think this is probably because my intermittent fasting diet already suppresses my hunger over the 18 hour periods I don't eat -- it has reset how my body responds to lack of food.

A few additional things I noticed:

* Colors seemed brighter after about 24 hours of fasting; the world seemed more alive.

* After about 30 hours of fasting and walking, I noticed that my breath felt a little different -- it was very subtle, but probably one aspect of the standard response when switching to keto mode.

* I felt lighter. Probably I was by a couple pounds (if you don't eat, your body has zero food weight).

....

One other thing: I'm also starting on 2 weeks of fisetin at 1000 mg per day. I bought some olive oil to mix it in (a quarter to half a tablespoon for 1 g dose), since I read that it enhances absorption.

The fisetin I bought was from Senolyfe. Each capsule has 250 mg, and a bottle contains 60 capsules; so, that will last me for 15 days.

Hopefully, it will cause my body to clean out senescent cells.
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