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In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’

nature.com

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Re: In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’

#81

Post by nikkwong »

kharak wrote: post #69
arcticbull wrote: post #57

Earlier quoted context omitted.

Fasting is easy and fun, you just have to work up to it. You can just go from zero to not eating for a week. Building up your tolerance to it takes a bit, like anything else, but when you do it improves mental acuity, gets you a general sense of well-being and energy too.

Uh, do you mean two weeks of only water? Do you do this for weight loss? Do you work out? I would be very afraid to mess-up my metabosm. How do you prevent that?

Long term or repeated fasting should actually decrease your body's metabolism rate; which is a good thing if you want to age slower. (I.e. think about species who have slow metabolisms, turtles, for one, who live very long lives). I do alternate day fasting (48 hour fasts, every other day) and realized I now need far fewer calories to get by than I used to. Obviously anecdotal but I feel great!

Re: In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’

#82

Post by nikolay »

jostmey wrote: post #26
magna7 wrote: post #9

I'd wager that it's the metformin. Metformin inhibits pathways associated with mTOR (the growth signaling protein). When you inhibit this pathway, it tells the body to start the process of autophagy. It's the same process that occurs during fasting, and it's the same reason that the mTOR inhibitor Rapamycin has been shown to extend lifespan in mice and dogs. This is also why fasting has been shown to increase lifespa…

Biology is not that simple. There's not going to be a single magic compound. Slowing the aging process is massively complex and will probably require a cocktail of treatments

I lot of people look at just one part of biology and totally ignore all the basics only focusing on aging reversal and living forever. First, autophagy is nice to have it done from time to time, not constantly. If you constantly activate it, then your cells will reach the Hayflick limit. So, you need to boost your telomerase... but then you can more easily get cancer.

The best strategy for me is lower metabolism, undereat, and reduce cellular damage and senescence. In some cases, senescence can be reversed (a friend of mine is doing a beta cell research at UCLA, and they've done that to some extent.) Of course, there are other strategies, involving stem cells, but I'm not familiar with that part - maybe they can compensate the negative effects of autophagy.

Re: In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’

#83

Post by nikkwong »

Can someone enlighten me as to why a study such as this one may be undertaken without a control group? I mean, what's the point? If the study ends up landing on some exciting conclusions, not having a control group creates more questions than answers. Is there a budgetary constraint at play here or are researchers sticking their feelers out in all kinds of directions simultaneously trying to figure out which direction may be the most promising?

Re: In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’

#84

Post by mdorazio »

scottlocklin wrote: post #66
toomuchtodo wrote: post #65

Earlier quoted context omitted.

Metformin is fairly safe as far as pharma goes; it requires a high dosage to be toxic, and the primary side effect is gastrointestinal distress. It's also a cheap generic (~5 cents/pill, costs me $2/month). It would be unfair to lump it in with the opioid epidemic, considering the differences. Would you not at least try to live a bit longer for only $25/year and a once a day pill?

Berberine is OTC. Not sure what relative risk profiles are. But yes, it's absolutely not comparable to opioids.

It seems Berberine and Metformin have different activation paths (Berberine might not lead to AMPK activation) and don't necessarily have exactly the same effects. Is there any research on the two being comparable for longevity purposes (other than lowering tumor risk)?

Re: In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’

#85

Post by busyant »

Amygaz wrote: post #29

I have no ef-inf clue why it was a total surprise. Metformim, is already known to affect in multiple ways the epigenetics, and the immune system. Also the so-called epigenetic clock is based on the observation that as we age we are more methylated. Reversing this has not been shown to be true, but it was shown to improve certain functions, like our production of T cells. This such a click-bait piss-poor paper I can’t…

> This such a click-bait piss-poor paper I can’t believe it’s in Cell.

There's a lot of politics in what gets published in prestigious journals like Cell (also, this paper was published in Aging Cell, so not quite as prestigious).

Amusing anecdote: In grad school, one of the profs in my department submitted a manuscript to Cell (this was back in the 1990s). His lab had done an amazing genetic study. There was a more famous lab at another University (run by a future Nobel prize winner) that had performed a complementary research study using an in vitro system. Both labs submitted their papers to Cell "back to back." Ben Lewin rejected the genetics manuscript (one reviewer said the genetics research belonged in a more 'archival' journal).

Lewin accepted the manuscript describing the in vitro work of the more famous lab.

A few months later, the anonymous reviewer was visiting our department (to give a talk) and he revealed himself as the reviewer to the professor who had submitted the manuscript. Professor asks, "I was honestly shocked by the review. was just dotting the Is and crossing the Ts of our research."

Reviewer responded with, "I thought [rejecting your manuscript was] what Ben wanted me to do." Probably did not help that the reviewer had been a post-doc in the famous prof's lab.

That's just one story that I am pretty familiar with. I have heard many others (e.g., famous prof telling editors stuff like " paper gets accepted or we will submit our next groundbreaking paper elsewhere."

Re: In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’

#86

Post by nikolay »

ALittleLight wrote: post #50
rwj wrote: post #10

The sample size is so small, that the results are nearly meaningless.

If 9 people took a substance and died that would be a compelling enough sample size for me not to take thing. Likewise, 9 people reporting a positive result seems meaningful enough to encourage further study (provided effect size is large enough)..

With the placebo being so strong, sample size of 9 is too small for any conclusion.

Re: In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’

#87

Post by efoto »

01100011 wrote: post #59
scottlocklin wrote: post #6

1) DHEA is not a diabetes med. In fact it's a steroid (not really an anabolic one, though it is a precursor to anabolics) and illegal in the EU. It is a substance which is lowered in older people, so older people supplement with it. 2) Metformin is a diabetes med, and it's used by antiaging enthusiasts independently and along with growth hormone 3) Fasting creates larger growth hormone spikes, and improves sugar clea…

44 yo male. DHEA is amazing. In times of stress, it restores my libido and ends my depressive cycle. I don't take it every day, but I definitely keep it close by.

"Studies have shown quality control of this supplement to often be low." [1] -- which one are you using?

[1] https://www.mayoclinic.org/drugs-supplements-dhea/art-203641...

Re: In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’

#88

Post by powersnail »

darkerside wrote: post #79
jostmey wrote: post #26

Earlier quoted context omitted.

Biology is not that simple. There's not going to be a single magic compound. Slowing the aging process is massively complex and will probably require a cocktail of treatments

Why do you say that? Biology is usually very simple. Eat food, live. Don't eat food, die. Drink water, live. Don't drink water, die. Just because you don't happen to know the answer doesn't mean the answer is complicated.

Just because you can say something in four words, doesn’t mean it is simple.

You eat, you live. Sure. But why? What happens to the things you eat? What can you eat? What/how/why is the pain in your stomachs?

Re: In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’

#89

Post by arcticbull »

nikkwong wrote: post #80
RandomTisk wrote: post #76

Earlier quoted context omitted.

Have you experienced additional mental acuity/focus first hand? Fasting for 24-36 hours for me isn't bad. But days 2 to 3 when I do a 3 day fast I find it extremely difficult to concentrate/focus on anything difficult. By day 3 my energy is usually shot as well and I just don't want to do anything but watch tv. If anyone has advice beyond sugar I'd love to hear it.

Are you supplementing with electrolytes? You need magnesium citrate + salt + potassium. Without that I can't achieve fasts longer than 48 hours.

That's definitely true, electrolytes make it much easier.

Re: In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’

#90

Post by driverdan »

nikkwong wrote: post #83

Can someone enlighten me as to why a study such as this one may be undertaken without a control group? I mean, what's the point? If the study ends up landing on some exciting conclusions, not having a control group creates more questions than answers. Is there a budgetary constraint at play here or are researchers sticking their feelers out in all kinds of directions simultaneously trying to figure out which directio…

Because the larger the group the more expensive it is to run. This is a very early experiment to see if there's anything worth doing a larger study on.
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