#1

Juan José Alba-Linares and his research team have published a preprint study that examined why different animals age at different rates. They found that epigenetic changes over time could explain why some animals live longer and estimated an upper limit for mammalian lifespan [1].

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#2

A nice study in summary: the problem is the faulty methylations that accumulate in DNA, these accumulate over time and prevent the DNA from being read correctly, which accumulates and causes tissue and organ dysfunction. So the important point is: How can we remove the methylations in DNA?

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#3

As far as I know, Yamanaka Factors are the only treatment that has been shown to (partially) reverse epigenetic age. There are also small molecule alternatives to some of the factors, but these would still need to be administered in very targeted and controlled ways due mainly to cancer risk. This thread gives an overview of some of those alternatives: Chemically induced reprogramming to reverse cellular aging

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#4

The researchers think this could mean that there is a natural limit to how long mammals can live, and they estimate that the maximum lifespan for any mammal, including humans, might be around 220 years.

It’s hard to imagine any mammal living to 220 years naturally (i.e. without any medical interventions). I wonder if they mean that it’s an absolute maximum lifespan of 220 years if medical interventions don’t include therapies to tackle DNA methylation.

#5

My epigenetic age at TruD has been going down.

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#6

It’s hard to imagine any mammal living to 220 years naturally

First I imagine a Bowhead Whale. It’s not that hard.

Then I imagine myself. :wink:

You have to set goals after all. :wink:

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#7

Human eggs do it too and do it perfectly!
(And equivalent in almost all species)

So any technology can grow organs and tissues or even non sentient bodies for replacement would also reverse your epigentic age (and with less risks of cancer than current Yamanaka Factor approaches).

(And such replacement ould replace the other forms of aging too that cell age reversal won’t be enough to fix)

Or what do you say @ng0rge

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#8

Methylations are like scars on DNA.

#9

There are de-methylation agents, but I think we’re still a long way from understanding how to target specific methylation we might want to eliminate, and understanding all the implications of different methylation patterns…

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#10

Love your optimism. It really helps in the morning in addition to a cup of coffee. Thank you. Believe and you will achieve!

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#11

Just wanted to clarify that this study actually shows that noisy CpGs correlate with aging REGARDLESS of hyper or hypo methylation, so in other words they correlate with aging whether there is more or less methylations. What they are saying is that it is the rate of entropy that is the predictor.

‘This result is noteworthy for several reasons. First, it provides evidence that the rate of epigenetic entropy gain is a genuinely informative measure of maximum lifespan, operating independently of the deterministic direction of methylation changes. Second, it shows that the accumulation of noise can be a more direct predictor of species lifespan than other proposed epigenetic indicators such as the rate of DNA methylation [8], a finding which is more biologically consistent with the information theory of aging [16].’

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#12

By the way - I stand corrected. It seems that research has progressed significantly in this area, as discussed in this thread: Editing the epigenome, Moonwalk Biosciences

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#13

Thanks for asking and I’m certainly following the epigenetics space. There is just so much going on, it’s hard to keep up. I’ve been doing hours of reading every day.

Moonwalk certainly looks interesting with both Attia and Kaeberlein listed as scientific advisors.
It’s hard to tell how much of the news coming out is hype since as I’ve mentioned there are 28 million CpG sites, some static but many constantly changing, being methylated/deacetylated or demethylated/acetylated sometimes on a daily bases. The static ones, that usually stay the same over the lifespan are the ones they are using to measure epigenetic noise or “epigenetic drift”. This is the basis of Irina Conboy’s Generation Lab Epigenetic clock. But this is just a small subset of the 28 million CpG. At least with these we know what to reset them to, because they are usually unchanging. An example would be the housekeeping genes that need to stay active.
—With partial cell reprogramming it’s less clear where you want to reset them to. You don’t want to regress them past cell differentiation to stem cells - or at least not all of them. Also epigenetics is like a cell memory, I’m not sure you want to erase it all. Seems very complicated and tricky, including the translation from mice to humans.

But in many cases it’s been difficult to determine which switches control what genes, or how to get to them without causing other problems. Using new computing tools and advances in genomic research, a number of biotech companies pushed ahead with research, and are now joined by others seeking to use CRISPR-based tools. Their idea is to use CRISPR components to turn genes on or off, or to alter the expression of several at a time without cutting into or changing DNA.

https://www.biopharmadive.com/news/epigenetic-gene-editing-crispr-epic-tune-chroma/627703/

“I think of the epigenome as a software of the genome,” Aravanis said, likening its ability to control gene expression to the technology used to encode websites and computer programs.

Moonwalk plans to harness that software with computing tools that, Aravanis claims, will help the company examine changes that occur during a biological process called methylation. Moonwalk will use that information to uncover which areas of the epigenome to target, and then go after them with editing technology licensed from Zhang at the Broad.

“People have tried to modify the epigenome, and there have been successes in the past,” he said. “But the broad technology to characterize it completely, modify it at multiple sites and to do it very precisely, that’s new.”

So, you might be able to reboot with a clean copy of Windows, but you’d still need to add back all your data and apps.

Current research has shown that transient expression of Yamanaka factors can rejuvenate cells in mice without fully reprogramming them to an embryonic state or risking de-differentiation into other cell types, suggesting potential for safe application in humans.

Just to show how fluid the epigenetic state is, take a look at this:

Epigenetic age can fluctuate by five years in a single day

https://www.pnas.org/post/journal-club/epigenetic-age-can-fluctuate-five-years-single-day

We often think of aging as a process of progressive methylation of DNA, silencing genes so they don’t function like they did when younger. But here’s a case where demethylating the DNA and activating the genes is what is causing the aging problem.

Cox said: “The human genome is full of bits of viral DNA that crept in there over our evolution, and they’re normally repressed. But as we get older, they jump out again and trigger inflammation, the body’s response to an infection. The problem is the immune system is also old, and so it can’t deal with it.”

https://www.theguardian.com/business/2023/nov/05/british-biotech-races-uss-buff-billionaires-for-secret-of-eternal-youth

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#14

I think the methylation is downstream of the aging process and will adjust with sufficient substrate for the TET enzymes (which is AKG).