Aging is associated with a systemic length-associated transcriptome imbalance | Hacker News Reader

Aging is associated with a systemic length-associated transcriptome imbalance

nature.com

50 pointsAnon8420 comments

Over 20 years ago, I watched a video by Aubrey De Grey that really impressed me. In the video, he presented a short list of "problems" associated with aging and described aging as a disease. I haven't received any updates on this topic in a long time. Is it still science fiction to think about living to be over 120 years old?

Not science fiction. 150 might be possible for some people alive now.

Andrew Huberman's interview with researcher David Sinclair mid-2022 well worth a listen for high level but technical coverage of state of play.

Yes, these people are avid promoters of their work, but they are doing the work.

There's no scientific reason to expect that anyone alive today will live to 150. It's purely based on conjecture and hope. If that was likely to happen then we would be seeing some incremental progress towards the goal already. But still we haven't seen anyone verified to live past 122. And she died in 1997.

Maximum lifespan is unimportant anyway. What actually matters is healthspan. If anything we're going backwards on that metric.

Change can happen gradually then suddenly. For example, massive human death due to disease, and then in the space of one human lifetime in the rich world the death rate from disease dropped incredibly fast.

In the space of one human lifetime maybe someone will invent a warp drive. I can't prove it won't happen. But since we're not making any concrete progress towards that goal it seems highly unlikely.

Same thing with extending human lifespan to 150. Let's see some actual scientific evidence. Otherwise it's just an expression of faith.

There is progress toward the goal. For example determining molecular and tissue markers of aging, research in mice, all the work funded by SENS Foundation and soon LEV Foundation, findings that for example giving blood from young mice to old mice restores some aspects of youthfulness, and so on.

That's interesting basic research but so far no one has established a clear causal connection to lifespan. It remains just conjecture.

Healthspan is super important, will be really cool to have a youngish person living to 130/140/150, but yes a healthy centenarian is really cool, too.

What do you think about his promotion of NMN? I was very excited at first, but looking at his past, it all seems very shady.

In 2004, Sinclair, along with serial entrepreneur Andrew Perlman, Christoph Westphal, Richard Aldrich, Richard Pops, and Paul Schimmel, founded Sirtris Pharmaceuticals. Sirtris was focused on developing Sinclair's research into activators of sirtuins, work that began in the Guarente lab. The company was specifically focused on resveratrol formulations and derivatives as activators of the SIRT1 enzyme; Sinclair became known for making statements about resveratrol like: "(It's) as close to a miraculous molecule as you can find. ... One hundred years from now, people may be taking these molecules on a daily basis to prevent heart disease, stroke, and cancer." Most of the anti-aging field was more cautious, especially with regard to what else resveratrol might do in the body and its lack of bioavailability. The company's initial product was called SRT501, and was a formulation of resveratrol. Five years later, GSK shuttered the Sirtris program without successful drug development.

Sinclair broadly discusses his longevity practices on social media and includes them in his book. They include daily doses of NMN and resveratrol, which Sinclair says are activators of SIRT1.

Studies published in 2009 and early 2010 by scientists from Amgen and Pfizer cast doubt on whether SIRT1 was directly activated by resveratrol and showed that the apparent activity was actually due to a fluorescent reagent used in the experiments.

https://en.wikipedia.org/wiki/David_A._Sinclair https://en.wikipedia.org/wiki/Sirtris_Pharmaceuticals

We just don't know about NMN. It appears to be generally safe, but no study has ever shown it to extend lifespan in primates. More research is needed.

https://peterattiamd.com/ama35/

I thought it drastically increased the rate of growth lf certain cancers?

Thanks! I don't mind the marketing, in fact, if there is good science behind it I totally support it.

> for some people alive now

what distinguishes those people?

It's a shame his company is gate keeping NMN now that he's created demand for it

Not science fiction, but the first people to start topping out at those ages consistently will likely have the right combination of wealth, lifestyle and good genetics.

Imagine job listings with 50 years minimum experience.

Lending and investing also become interesting at these timespans.

And insurance

Amazing! Another step forward in defeating aging!

So we just intersperse random bases?

that seems precarious, considering they're blueprints for proteins with particular mutually compatible geometries.

that seems like splicing in random stuff in a bunch of Legos, and noticing that the set of resulting pieces no longer can build a Lego rocket, for example.

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