5 ms·

Cell-Aging Hack Opens Longevity Research Frontier

103 points by ph0rque 15y ago

reasonattlm 15y ago
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-accumulate-senescent-cells-anyway.php 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-of-the-merits-of-apoptosens.php http://www.fightaging.org/archives/2011/11/a-demonstration-o... The paper: http://dx.doi.org/10.1038/nature10600 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 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.cfm http://discoverysedge.mayo.edu/de07-2-aging-vandeursen/index...
jakeonthemove 15y ago
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...
- reasonattlm 15y ago
  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.
  - usaar333 15y ago
    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?
    - reasonattlm 15y ago
      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-Breakthroughs-Lifetime/dp/0312367066 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-that-is-the-fda.php 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.php 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-cancer-does-not-worry-me.php 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/SIAAR-PP.pdf http://www.sens.org/files/pdf/A4M04-PP.pdf http://www.sens.org/files/pdf/A4M04-PP.pdf
suivix 15y ago
Genetically engineering something for this specific goal is not a 'hack'. It's very hard and thorough work.
- artursapek 15y ago
  It's alteration of an established system with self-beneficial results in mind. It's a hack.
  - suivix 15y ago
    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.
    - phuff 15y ago
      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.
    - artursapek 15y ago
      I think it's glorification that's the problem. I would consider medicine a hack, hacks aren't divine achievements.
  - rhino42 15y ago
    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.
tryitnow 15y ago
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.
- lukev 15y ago
  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.
  - srl 15y ago
    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.

103 points by ph0rque 15y ago

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-accumulate-senescent-cells-anyway.php 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-of-the-merits-of-apoptosens.php http://www.fightaging.org/archives/2011/11/a-demonstration-o... The paper: http://dx.doi.org/10.1038/nature10600 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 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.cfm http://discoverysedge.mayo.edu/de07-2-aging-vandeursen/index...

jakeonthemove 15y ago

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...

reasonattlm 15y ago
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.
- usaar333 15y ago
  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?
  - reasonattlm 15y ago
    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-Breakthroughs-Lifetime/dp/0312367066 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-that-is-the-fda.php 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.php 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-cancer-does-not-worry-me.php 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/SIAAR-PP.pdf http://www.sens.org/files/pdf/A4M04-PP.pdf http://www.sens.org/files/pdf/A4M04-PP.pdf

suivix 15y ago

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

artursapek 15y ago
It's alteration of an established system with self-beneficial results in mind. It's a hack.
- suivix 15y ago
  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.
  - phuff 15y ago
    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.
  - artursapek 15y ago
    I think it's glorification that's the problem. I would consider medicine a hack, hacks aren't divine achievements.
- rhino42 15y ago
  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.

tryitnow 15y ago

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.

lukev 15y ago
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.
- srl 15y ago
  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.