Telomerase: TERT activation targets DNA methylation and multiple aging hallmarks

Restoring youthful levels of specific subunit of telomerase enzyme reverses multiple hallmarks of aging in mice. Study in Cell Press shows maintaining TERT levels in aged animals reduced cellular senescence, improving memory & neuromuscular function.

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TERT activation targets DNA methylation and multiple aging hallmarks

Highlights

  • TERT has been linked directly or indirectly to all hallmarks of aging

  • TERT gene is epigenetically repressed with onset of aging markers in all tissues

  • TAC restores TERT levels to promote telomere maintenance and reprogram gene expression

  • TAC in aged mice reduces senescence/inflammation and increases neurogenesis/cognition

Paywalled Paper:

https://www.cell.com/cell/abstract/S0092-8674(24)00592-0

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Elsevier blocks access of the full paper via TOR browser…

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So, how do we get ahold of some TAC?

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It’s a simple enough compound I could probably get some made, if there’s enough of a market of educated folks.

But there’s no human safety data (or even proper animal safety tests in the paper). Generally I don’t like people trying things without at least phase I style testing. In this case the hit and run dosing makes the risks a bit smaller, but we should maybe consider repurposing existing drugs to hit the same pathway.

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I was kinda joking about getting some, but there are people on this board who would try pretty much anything.

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Screenshot 2024-06-25 at 11.10.07 AM

See also: Possible side-effects of sulfonamide drugs

Telomere length is not a limiting factor for longevity (yet) and risk of cancer from this treatment is high. Unless you are 120 already I’d wait.

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Telomere length is not a limiting factor for longevity (yet)

Exogenous TERT increases female mice lifespan by about 27-28% (relative to a 900 day control), when given at the equivalent age of a 56 yr old human. Larger sample size studies would be nice, but I think it’s already clear that telomerase is quite possibly a limiting factor in human longevity as well. Keep in mind, mice die more easily from cancer than humans.

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TAC was shown to reach numerous tissues and organs, including, importantly, the central nervous system, and to be cleared from the organism in about three hours.

This, according to the researchers, was enough to improve multiple hallmarks of aging.

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From the GRG mailing list:

a member identified TAC as N-(3-chloro-4-fluorophenyl)-4-fluoro-3,5-dimethylbenzenesulfonamide or C14H12ClF2NO2S, and it looks like this:

N-(3-chloro-4-fluorophenyl)-4-fluoro-3,5-dimethylbenzenesulfonamide.png.

MolPort in Latvia will sell you 100 mg of 90% pure N-(3-chloro-4-fluorophenyl)-4-fluoro-3,5-dimethylbenzene-1-sulfonamide made by Maybridge, Ltd. for a total price of $241.43 and can ship in about 2 weeks . The scary part is that it is 90% pure and one doesn’t know anything about the other 10%.

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I like the idea of a topic for things not to try until you are 120. The real forbidden magic for necromancers only.

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90% you win immortality / 10% you lose and die a horrible painful death. Mmmm. Choices… :joy::joy::joy:

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New article about the same paper: https://scitechdaily.com/longevity-breakthrough-new-treatment-reverses-multiple-hallmarks-of-aging/
Simply allowing cells to divide more times wouldn’t help with certain cells that divide rarely, like neurons. So this line was interesting:

“The researchers also observed that certain cells, such as neurons and cardiac cells, were rejuvenated without undergoing the normal cell division required to synthesize telomeres.”

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