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Age Reduction Breakthrough?

joshmitteldorf.scienceblog.com

291–300 of 426 posts

Re: Age Reduction Breakthrough?

#291
post #290

Earlier quoted context omitted.

While I generally support these efforts, I have feeling it would be easier to engineer a way to escape these meat bag prisons we live in, and construct an android body that isn't built from the worst form of spaghetti DNA code imaginable.

The eternal struggle between "rewrite it from scratch" and "build upon legacy code"

In this case, we're trying to build upon compiled assembly code that's been re-obfuscated every generation.

I'm not even kidding. Almost every protein in the human body has multiple unrelated functions, just because evolution says "hey, this is here, let's use it for something new".

Every new human is an experiment in code chaos.

Re: Age Reduction Breakthrough?

#292
post #67

Earlier quoted context omitted.

People who had this mutation could have died of causes other than aging.

On a long enough timeline, can't we assume that pretty much everyone is going to die of cancer?

Elephants are massive, and have a very large number of cells compared to humans, yet their rates of cancer aren't higher than ours. Research indicates that it may be due to TP53, a cancer suppression gene that is repeated a ton in the elephant. I could see anti-aging therapy eventually being used in conjunction with gene therapy to strengthen our own tumor suppression capacity.

Re: Age Reduction Breakthrough?

#293

Since it seems like the upshot of all of this is that Katcher is claiming to have discovered a set of signalling molecules which, when injected, rejuvenate tissue and presumably lengthen life, it runs into one of the most fundamental objections that can be leveled at theory of aging (or cure thereof): of the billions of humans that have existed, how is it that none of them have possessed a mutation which (in this cas…

tl;dr: this is not an "age reduction breakthrough", it is both A) a confirmation of what we already knew, which is that parabiosis makes old mice healthier, and B) a finding that virtually proves the mAge clock has nothing useful to say about lifespan

Parabiosis does not substantially extend lifespan (possibly not at all), based on the experiments done so far. Even if it did, it definitely does not double it, which is what would be predicted by naively looking at the halved DNA mAge on the clock.

This paper is very likely intended as another validation of Horvath's mAge clock. The clock shows that there is a strong association between epigenetic state and both chronological age and morbidity risk. Exactly why that is, and what it means, is highly controversial.

Mainstream aging field does not really care about lifespan much anymore. Increasing amount of focus is on so-called "healthspan" - approximately the duration of healthy life, or incidence of morbidity. You would think that you could not affect one without the other, but in fact you can, to a frustrating and surprising degree.

Therefore when you read about "rejuvenation", we are increasingly finding that you can find treatments which improve a broad spectrum of unrelated health markers, that these treatments will affect epigenetic loci predictive of age, and all of this without any substantial effect on lifespan. (From a public policy perspective, this is considered highly desirable, as for public expenditures it would be ideal if people lived perfectly healthy until the moment they keel over, even if we cannot extend the time until they do)

One possibility to keep in mind is that rodents die almost entirely of cancer. So it is possible that some treatment which improves "everything except cancer" would not show any lifespan effect in rodents. This would be one way of reconciling this paper with Horvath's earlier finding that the clock predicts all-cause mortality in humans.

Re: Age Reduction Breakthrough?

#294

It's impossible for an old cell to become young again, at least with our current level of technology, because that would require you to reverse all the mutations that have built up over time in that cell. If your argument is that our bodies have many different repair mechanisms, and that as long as we can figure out how to activate them properly, we can then reverse aging, I would caution you that while you're correc…

> It's impossible for an old cell to become young again, at least with our current level of technology.... Depending what you mean by "become young again," that's not true. See https://med.stanford.edu/news/all-news/2020/03/old-human-cel... The problem here is scaling this up beyond tissue cultures.

Again, I emphasize this point:

> I would caution you that while you're correct in that repair mechanisms do exist, it's important to remember that these mechanisms are themselves composed from the same components as the rest of your body, i.e. they too will age and begin to fail over time.

The process of nuclear reprogramming to induced pluripotent stem cells, which is the subject of your referenced paper, is something that I believe to be a great scientific breakthrough, but nevertheless fails to address the accumulated mutations that build up over time in your cells. All those mutations don't just magically disappear.

Re: Age Reduction Breakthrough?

#295

Earlier quoted context omitted.

> It's impossible for an old cell to become young again, at least with our current level of technology.... Depending what you mean by "become young again," that's not true. See https://med.stanford.edu/news/all-news/2020/03/old-human-cel... The problem here is scaling this up beyond tissue cultures.

Again, I emphasize this point: > I would caution you that while you're correct in that repair mechanisms do exist, it's important to remember that these mechanisms are themselves composed from the same components as the rest of your body, i.e. they too will age and begin to fail over time. The process of nuclear reprogramming to induced pluripotent stem cells, which is the subject of your referenced paper, is somethi…

Sure, but, presumably, in most cases, you can repeat the therapy. And, if such treatments are shown to provide additional healthy years, who cares, even if they're not repeatable? I'd pay for a treatment that could be shown to add years to my life expectancy.

Re: Age Reduction Breakthrough?

#296

Earlier quoted context omitted.

There are some animals that don't "age" like we do. These animals can live indefinitely, until they are eaten or die in some accidental way. Aging is a set of complex bio-physical-chemical processes. We have actually made a lot of progress in recent decades understanding how this happens. There is no fundamental reason we won't be able to better understand these processes and then mitigate them heavily, if not entire…

I'm terrified. Imagine the current crop of elderly rich mostly white men in positions of political power. Now imagine they're never going to die or retire. Sounds pretty dystopian to me.

No post body was provided.

Re: Age Reduction Breakthrough?

#297

Earlier quoted context omitted.

Again, I emphasize this point: > I would caution you that while you're correct in that repair mechanisms do exist, it's important to remember that these mechanisms are themselves composed from the same components as the rest of your body, i.e. they too will age and begin to fail over time. The process of nuclear reprogramming to induced pluripotent stem cells, which is the subject of your referenced paper, is somethi…

Sure, but, presumably, in most cases, you can repeat the therapy. And, if such treatments are shown to provide additional healthy years, who cares, even if they're not repeatable? I'd pay for a treatment that could be shown to add years to my life expectancy.

There are drawbacks that you should consider. Many of the repair mechanisms that exist, which later on become deactivated, are turned off for a reason.

It's important to understand that renewed growth is synonymous with cancer. The older you are, the greater the risk you face as your fail safes and redundancies begin to fail from corruption due to accumulated mutation. It's often better to completely turn the thing off, which is exactly what your body does, after a certain point.

The older you get and the more you age, the more you should focus on preventing the development of cancer over anything else as that will likely have the greatest impact in determining your life expectancy, assuming you continue to stay active, eat properly, and get enough sleep.

Re: Age Reduction Breakthrough?

#298

Earlier quoted context omitted.

It's weird to me to say so but this intervention is one of the few things that, even if it were to demonstrably increase my lifespan from ~80 to ~120 years, I probably wouldn't do. I don't know if that's because I enjoy food and bodily activity too much to value a longer life without them or because I'm addicted to food. I've wondered. What wouldn't you be willing to give up for a much longer life?

there is a huge difference between enjoying food and being a slave to food. the best example I have in this bucket is sugar. If you depend on sugar you're basically a drug addict (i know, i know, but just because it's socially acceptable does not make it okay. there is research out there that show sugar is as bad as cocaine when it comes to how addictive it is and on the health effect). if you could pick just one int…

Well we were talking specifically about reducing calories by something like 50%, which automatically cuts out sugar, grains, probably meat. But what really kills it for me is not being able to move, dance, play sports.

I understand how people can have fulfilling lives after losing the ability to do those things. Would I voluntarily give them up for a longer life? Probably not.

Re: Age Reduction Breakthrough?

#299

Earlier quoted context omitted.

It's weird to me to say so but this intervention is one of the few things that, even if it were to demonstrably increase my lifespan from ~80 to ~120 years, I probably wouldn't do. I don't know if that's because I enjoy food and bodily activity too much to value a longer life without them or because I'm addicted to food. I've wondered. What wouldn't you be willing to give up for a much longer life?

Depends which parts gets prolonged - if you are at 80 deteriorated +-same as somebody who dies at 80, and they just keep fixing the next thing that is going to kill ya, then yes, that's a pure physical misery and spiral down progressive dementia (almost all old folks suffer from some form of it). Now if we would be 40-like in our 60s and so on, that's another story. But first thing that would probably change is retir…

Is being 40 and not being able to play tennis or go on long walks because you're too calorie-deprived that different from being 80?
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