Cell-Aging Hack Opens Longevity Research Frontier | Hacker News Reader

Cell-Aging Hack Opens Longevity Research Frontier

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103 pointsph0rque26 comments

The mice used in this study are a breed engineered to suffer accelerated aging, which means it doesn't have too much to say about what will happen in normal mice: this study adds weight to arguments for the importance of senescent cells in aging by virtue of the degree of change that was produced. To my eyes, the important outcome here is the development of a reliable way to flush out senescent cells in mice - which can now be applied to otherwise normal mice to see what happens there. Will they live longer, what will their risk of age-related disease be, etc?

For further reading on senescent cells, see:

http://www.fightaging.org/archives/2008/06/why-do-we-accumul...

For commentary on this research:

http://www.fightaging.org/archives/2011/11/a-demonstration-o...

The paper:

http://dx.doi.org/10.1038/nature10600

"Senescent cells accumulate in various tissues and organs with ageing and have been hypothesized to disrupt tissue structure and function because of the components they secrete. However, whether senescent cells are causally implicated in age-related dysfunction and whether their removal is beneficial has remained unknown. To address these fundamental questions, we made use of a biomarker for senescence, p16Ink4a, to design a novel transgene, INK-ATTAC, for inducible elimination of p16Ink4a-positive senescent cells upon administration of a drug."

Running this method in otherwise normal mice rather than the BubR1 accelerated aging mice used here will be an important test of the merits of research programs like the SENS Foundation's apoptoSENS:

http://sens.org/sens-research/research-themes/apoptosens

But it will be at least another five years, I'd imagine, to get the results of a life span study in ordinary mice, even if they turn right around and start pulling down the grants right now.

The BubR1 mutant progeria-suffering mice used in this work are discussed in a good article at the lab website:

http://discoverysedge.mayo.edu/de07-2-aging-vandeursen/index...

One thing people lose sight of is what I call the "whack a mole" problem. If we spend a ton of money fighting the big killers, but doing little to focus on rejuvenation therapies then we will just keep succumbing to a different set of diseases even if therapies help us beat back the diseases we would have succumbed to without them.

For example, let's say I have diabetes. Then let's say some genius finds a complete cure for it. Ok, so it's not going to kill me now. But now I'll probably just succumb to heart disease. Let's say we cure that. OK, then cancer will get me. It's like the "Whack a mole" game at an arcade - you beat one disease down, but another one always pops up to get you.

This happens because so many of the killers in the developed world are really tied to the aging process. So really "curing cancer" or "ending heart disease" will just buy us minimal time. My bet is the economic benefits of a cure for cancer in older adults* would not be as great as people realize. At best it will buy us a few more years of low quality of life.

Targeting aging on the other hand allows us to "strike at the root" of the problem. Many of the cures and therapies attracting money now are just temporary hacks applied to a system that is slowly accumulating so many bugs that it's just never going to make it.

The "cure aging" meme sounds ridiculous and in truth, it is pretty ridiculous. However, curing any of the big killers is going to require a level of effort commensurate to curing aging, so why not invest scarce resources in targeting the root problem?

*Curing cancers in the young will have an economic benefit that more than covers the costs since the young have more years of economically productive life ahead of them. This is also why targeting diseases like AIDS tend to be economically worthwhile.

But the inverse problem also exists. Cure aging, great... but if you haven't also cured cancer and heart disease, your life still isn't likely to be that much longer.

We need to attack the problem on all fronts.

Also, it's worth pointing out that whether we "cure aging" is not a boolean proposition. All we can talk about is increasing the average lifespan. Curing cancer and heart disease will definitely do that.

He's saying that aging is a major contributor to cancer and heart disease (or at least, that we think it is). This is true. "Curing aging" means a dramatic reduction in the overall rates of cancer, heart disease, etc.

Curing aging would imply that humans would have a theoretically infinite life expectancy, modulo the various other things that kill us, which have a certain chance of occurring per unit time, based on various factors. In practice, that does mean a finite lifespan, but it vastly amplifies the effectiveness of any other cures or treatments we devise. That would entirely change the dynamic of many forms of disease prevention and cure. Suddenly, fighting diseases would no longer have a shadow of "staving off the inevitable", particularly in the elderly or those faced with chronic illness.

So, sure, we need to continue playing whack-a-mole, but we need the cure for the fundamental bug too.

Also, it's worth pointing out that whether we "cure aging" is not a boolean proposition. All we can talk about is increasing the average lifespan.

No matter how well you take care of yourself, you're going to be significantly less healthy at age X+20 than at age X if X>25. Curing aging would mean that would no longer be true. There would no doubt be diseases remaining, but your susceptibility to them would be that of a 25 year old regardless of your biological age.

> For example, let's say I have diabetes. Then let's say some genius finds a complete cure for it. Ok, so it's not going to kill me now. But now I'll probably just succumb to heart disease. Let's say we cure that. OK, then cancer will get me.

Just wanted to point out that the diseases you mention, type 2 diabetes, heart disease, many cancers, etc. are diseases of the western world and in many cases preventable.

Heart disease and Cancer are not a disease of the western world in that you can find plenty them thought the world. The reason we see more of them in the "western world" is because you are far more likely to see them as your age increases and the western world has a lot more 'old' people than anywhere else.

PS: By old I mean 40+. And yes Japan has 1/3 the heart disease deaths, but when compared to the 1/10th obesity rate and better healthcare system it's not all about fat.

While our social welfare system isn't set up for it, it seems to me that if you make it 65 and feel not merely okay, but 20 years younger, there's no reason not to keep working (and thus paying for your care).

> One thing people lose sight of is what I call the "whack a mole" problem.

Not that you said so, but I want to stress that the oversight you talk about isn't entirely involuntary. There a good deal of refusing to look at the problem, while trying to solve it anyway.

Looking at the Wikipedia page about the causes of death, I only see problems that few would not want solved. Plus, it seems to be exhaustive, so whacking every mole on this list would effectively Cure Death. But when I talk about it directly (as in "let's cure death"), reactions ranges from "it's impossible" to "why would you want to be immortal?"[1], to "that would be horrible!"[2]. Religion can also get in the way (though not systematically).

[1]: http://tvtropes.org/pmwiki/pmwiki.php/Main/WhoWantsToLiveFor...

[2]: http://tvtropes.org/pmwiki/pmwiki.php/Main/ImmortalityImmora...

THIS is what people with money should focus on. Instead of buying cars, houses and islands, drop a few million into longevity research - the more resources, the faster it will go, and a way to stop aging will inevitably be found.

I guess it sounds crazy and impossible to defy death itself, that's why bio-research is so stalled compared to any tech field...

The projected cost estimate for a crash program with a 50/50 shot of realizing SENS in mice in ten years is $1 billion - meaning achieving robust rejuvenation of old mice.

It is an ongoing and interesting debate as to why funding of aging research by wealthy people is not more extant. See Larry Ellison's not very vocal interest in the field - he puts a fair amount of money into what amounts to a private arm of the NIA, which is to say he's not getting much in the way of progress for his funding. Or look at Paul Glenn's somewhat better aimed funding of ways to slow aging via the establishment of the Glenn Laboratories in a variety of research centers. Or Peter Thiel's $3 million for SENS research a few years back. These things are on a line from worst to best in terms of ways to achieve extended youth and repair aging.

But beyond that, there isn't much going on. When you compare and contrast with the behavior of wealthy people who suffer from a named medical condition, the disparity in action becomes clear. The biggest challenge is not so much the technical side of things - the path to repairing aging is as clear as things ever get in science - but the fact that very few people seem in any way interested in achieving this goal.

Given how little we know about stopping aging, and that blocking senescence also requires having a cure for cancer which society has thus far failed to find after spending something like $10B a year on it, I'm extremely skeptical of your claim about cost and time frame. Do you have a source for that?

We in fact know a very great deal about stopping aging. This book is a crash course in the science and what it means:

http://www.amazon.com/Ending-Aging-Rejuvenation-Breakthrough...

If it wasn't illegal to commercially develop ways to treat aging, there would be a lot more progress than has happened to date.

http://www.fightaging.org/archives/2010/03/the-roadblock-tha...

Making humans immune to cancer in the SENS proposals is accomplished via this methodology:

http://www.fightaging.org/archives/2008/06/complicating-wilt...

But from where I stand, watching research fairly closely for some years, I'm not particularly worried about cancer - the next generation of targeted and immune therapies under development now will be highly effective, and are looking very good in the laboratory:

http://www.fightaging.org/archives/2010/01/the-prospect-of-c...

The $1 billion figure for realizing SENS is referenced in these items; I'm not aware of a full line item breakout:

http://www.sens.org/files/pdf/SIAAR-PP.pdf http://www.sens.org/files/pdf/A4M04-PP.pdf

I think clearly the goal needs to be better branded/marketed to the public - that there's sort of a "you can't get there from here" problem with the "cheat death!" line being pushed by de Grey/Kurzweil vs. the current mindset, and as an even bigger problem is simply that death is an uncomfortable topic to really talk about head on for most people, and it leads to a lot of avoidance/rejection

If it could be promoted as something like, live healthier, longer (and really you're very likely to still be killed off by cancer eventually, so I very much doubt v1.0 life extension would see many/any 120+ lifetimes), it would be a much, much easier sell. Feel like you're 40 when you're 75 - that sounds great. Live forever sounds like nerd heresy

And, if you can pull that off and build up a big population of healthy 100 year olds, then you've got a base who says hey, this is pretty good, maybe we should shoot for 200 after all? And so on...

We won't have that tech at any point soon anyway, and so at this point the vaporware is killing the product

There are a lot of smart people who pour money into the research, but it's definitely not enough of them. Not to mention that the wealthiest of the wealthy don't seem interested, as you said.

I guess it's because it seems so incredible - I mean, even I can hardly imagine what living completely healthy up to 100+ years or living 200+ years must be like, so those who never thought about it must be like "what the heck are you talking about, crazy person?"

A few million? Is that you, Dr Evil?

Wealthy people are old and smart so they realize that it most likely is to late for them.

Genetically engineering something for this specific goal is not a 'hack'. It's very hard and thorough work.

It's alteration of an established system with self-beneficial results in mind. It's a hack.

Is a very complex alteration involving modified DNA and extensive research and testing. Everything is established until you change it. Most medicine is just a chemical compound you ingest, which would mean they are all 'hacks' with your perspective. The word trivializes the whole process.

The process isn't a hack, but the end result is :) Not a "quick and cheap dirty hack" but a "I've manipulated a system to do something different or better in a novel way" sense of a hack.

My wife had epidurals during the delivery of our children. That, even though it was a medical procedure, was totally a hack :) Inserting novacaine into the spinal column to deaden nerve receptors == hacking the body :)

That doesn't mean it wasn't serious business or a big deal. It just means that we figured out a neat way to manipulate an existing system for beneficial results.

I think it's glorification that's the problem. I would consider medicine a hack, hacks aren't divine achievements.

Really, all technological improvements in the last few centuries are "hacks" then, in a sense.

Each time we write a piece of software, we are taking an existing system (a computer), and altering it to perform a somewhat different task. Hack.

Each time I optimize a DSP system to take 10% less resources, its a hack.

Just stick 100 or 200 of these together, and we have moore's law.

That definition is so broad, it could be applied to almost any action that has benefit. Foe example, would mean that warming bread to make it crusty and crunchy is a hack?

I understand your position, as you see a 'hack' as a quick and dirty trick to make things work; but in this instance, hacking is taking on its more pure form of manipulating something according to the rules of the system it exists in, in a way that was not originally understood or intended :)

It's very much a hack.

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