7 ms·

Root molecular cause of declining health in the old found by scientists

45 points by bootload 16y ago

bootload 16y ago
From the article: ".. The scientists found that the basic cause of age-related health decline is malfunctioning telomeres — the end caps on cells’ chromosomes that protect them against DNA damage ... DePinho published a study in Nature in January 2011 that demonstrated it was possible to reverse the symptoms of extreme aging in mice by increasing their levels of telomerase, the enzyme that maintains the health of the telomeres ..." A bit late. Elizabeth Blackburn won the nobel prize for physiology in medicine 2009 for ... "... The trio has been credited with creating a new field of science, with their investigation of chromosomes and the discovery of an enzyme which they named Telomerase. Telomerase is almost like an anti-ageing solution - it is critical to the regeneration of cells, which are the building blocks of life. If cells cannot replenish, humans are more prone to disease. ..." ~ http://www.abc.net.au/news/stories/2009/10/05/2705473.htm http://www.abc.net.au/news/stories/2009/10/05/2705473.htm
- stcredzero 16y ago
  Also, mice do not suppress their telomerase. Without telomerase, tumors have a hard time getting larger than a golf ball. This is why large mammals like humans actually suppress telomerase expression in most cells. We might survive a golf ball sized tumor. A mouse? No way! There's no value in a mouse suppressing telomerase, so they're designed to have it switched on all the time. Would we want our telomerase to be switched on all the time? This would probably make us abnormally prone to developing cancer. This is also why whalers find tumor scars in whales all the time, but never run across whales that are going die of cancer. It's hard for a tumor to get larger than the size of your head. For us, this would likely be fatal. For a whale, it's no big deal.
  - ShardPhoenix 16y ago
    While you probably wouldn't want full-on telomerase in your 20s might be worth the risk if you're pushing 80 :).
    - stcredzero 16y ago
      While you probably wouldn't want full-on telomerase in your 20s might be worth the risk if you're pushing 80 :). Actually, you are much more at risk for cancer in your 80's. That might be the worst possible plan. There are 7 distinct classes of damage that comprise the wear and tear resulting from aging. Addressing telomeres only addresses one of these. Read and learn: http://www.scribd.com/doc/522716/Aubrey-de-Grey-SENS http://www.scribd.com/doc/522716/Aubrey-de-Grey-SENS http://www.sens.org/ http://www.sens.org/
      - ShardPhoenix 16y ago
        My point is that you're probably going to die soon anyway, so even with the cancer risk the treatment may well be +EV. Similar to how people are more willing to undergo risky medical treatments when they're already dying.
  - TheEzEzz 16y ago
    That is an interesting trade off. Still good new though, in my opinion. Cancer seems much more tractable than aging. If we can reduce the problem of aging to something that only requires us to additionally solve cancer, I would be ecstatic.
    - siganakis 16y ago
      One of the things that cancer is good at is switching "on" telomerase (enabling the cancer to spread), so naturally working out how to switch "off" telomerase in cancer tumors has actually been one of the key vectors in cancer research.
    - stcredzero 16y ago
      Cancer and aging are really the same problem. If we solve the other 6 forms of molecular damage and dysfunction, but don't solve the problem of cancer, then we all just get to be healthy for about a century, as if we're in our prime, but then die horribly of cancer.
  - kiba 16y ago
    If we shorten all the telomerase in our body to the point where cancers can't do much more than grow to beign side tumor, cancer is prevented from killing us ever. On the other hand, we must replace all our cells periodically with the same shorten telomerase.
    - stavrianos 16y ago
      careful here- I'm fairly certain there's more to cancer than just tumors.
      - SapphireSun 16y ago
        Well the major danger from what I understand is tumors metastasizing all over your body. On the other hand, certain special kind of gland cancers start over or under producing vital hormones (for instance tumors of the adrenal glands can induce massive doses of cortisol and/or adrenaline). That ain't so good for you.
- sorbus 16y ago
  The news is actually further down in the article: they've figured out the processes by which telomeres cause these effects.
- martey 16y ago
  I am (unfortunately) not a biologist, but the abstract of their paper in Nature [1] seems to suggest that their research is notable not because they discovered telomerase is related to ageing, but because they figured out why lack of telomerase causes cells to stop regenerating and organs to fail: We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1α and PGC-1β promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere–p53–PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction. [1]: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature09787.html http://www.nature.com/nature/journal/vaop/ncurrent/full/natu...
- jforman 16y ago
  This paper is significant because it finds a precise molecular mechanism whereby reduced telomere function affects organ health. From the article, "We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1α and PGC-1β promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere–p53–PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction." Physorg isn't the most reputable science journalism around (heh), but Nature is arguably the most prestigious journal for life science in the world, and everybody involved in the process of publishing this paper, and writing the News & Views article about it, is aware of Elizabeth Blackburn and telomere research. The more we know about the pathways involved, the more avenues we have for drug development.
- mkramlich 16y ago
  good point. but from the sound of it, this finding too will likely earn a Nobel. we're talking about something which is very likely a subset of what's going to either achieve immortality, or cure/prevent cancer, or do both!
mindcrime 16y ago
Interesting stuff. I know it's just a small step, but it makes you wonder if maybe good ole Ray Kurzweil is onto something with his talk about achieving immortality. Which leads to some interesting questions... if there was a drug available that would let you live to be hundreds or thousands of years old, barring accident, would you take it? What would be the effect on society if death were all but eliminated? Would our population quickly overrun the limits of Earth's resources? Thinking about this almost feels like an episode of The Twilight Zone.
- thewordis 16y ago
  Personally, I've been hearing all my life about the Serious Philosophical Issues posed by life extension, and my attitude has always been that I'm willing to grapple with those issues for as many centuries as it takes. -- Patrick Nielsen Hayden
- Zak 16y ago
  I'd take it without a second thought. I've talked to a number of people who wouldn't though, and I find that curious. Why would you choose death by aging if it was optional? Suicide by other means would still be available if you grew tired of life.
  - mindcrime 16y ago
    I'm with you; but I can imagine a few reasons why people might not take it. Some really religious types might feel that it's "playing God" or somehow interfering with "God's plan for the world." Some really eco-focused types might feel that it's immoral to live that long and therefore consume even more natural resources. Some conspiracy nuts would assume it was part of a government plan to do $SOMETHING. And some people might just assume there would be some sort of unforeseen consequences. Still, I bet most people would take it, and pretty quick.
    - jerf 16y ago
      Stepping up one meta point, a lot of people aren't actually teling you what they want, they're just flashing various social signals. As you say, put the pill in their hands, and, well, don't leave any of your body parts between their hands and their mouths if you don't want a nice new red welt. Yes, there are some who would not for real, but one wonders how even they would feel five years in.
bluekeybox 16y ago
Don't see anything new in the press release. Everything it states has been known for several years at least. Wish there was a link to the original study, but all links are either advertisements or internal links. The harvard.edu on the bottom does no good. What is the point of such press releases?
- hartror 16y ago
  They even gave a Nobel prize for the basis of this work like a year or two back.
SoftwareMaven 16y ago
So is the "news" here that the telomeres are the root cause rather than a contributing cause? I'm not seeing anything else I didn't know.
reasonattlm 16y ago
The popular press pieces are, as usual, breathlessly overhyped. Some commentary on this: http://www.fightaging.org/archives/2011/02/another-proposed-link-between-short-telomeres-and-dysfunctional-mitochondria.php http://www.fightaging.org/archives/2011/02/another-proposed-... "it is certainly the case that damaged mitochondria and shortening telomeres are only two of the possible reasons we suffer age-related degeneration. Many of the other causes of aging involve a build up of varying forms of damaging waste product that the body cannot remove - mechanisms which are quite capable of causing disability and death on their own, telomere shortening or no telomere shortening. "That said, telomeres, mitochondria, and p53 are all large and healthy areas of research when it comes to the biology of aging. I imagine that anyone would be pleased to produce good evidence that might mechanically tie them all together, such that one or more are secondary effects rather than primary causes. From an economic perspective, we should all be hoping that some of our present candidates for the primary causes of aging turn out to be secondary effects - because then we don't have to devote any time towards developing repair biotechnologies to fix them. "On a closer reading of the new research, I have to say that it looks to me very much like an independent confirmation of discoveries from 2007 and 2008 relating to mitochondrial damage, telomere length, and the enzyme telomerase. In a nutshell, it may be that telomere shortening is entirely driven by mitochondrial dysfunction" Etc. Links to more in the post.
lincolnpark 16y ago
Oh no! singularity is playin itself out

45 points by bootload 16y ago

From the article: ".. The scientists found that the basic cause of age-related health decline is malfunctioning telomeres — the end caps on cells’ chromosomes that protect them against DNA damage ... DePinho published a study in Nature in January 2011 that demonstrated it was possible to reverse the symptoms of extreme aging in mice by increasing their levels of telomerase, the enzyme that maintains the health of the telomeres ..." A bit late. Elizabeth Blackburn won the nobel prize for physiology in medicine 2009 for ... "... The trio has been credited with creating a new field of science, with their investigation of chromosomes and the discovery of an enzyme which they named Telomerase. Telomerase is almost like an anti-ageing solution - it is critical to the regeneration of cells, which are the building blocks of life. If cells cannot replenish, humans are more prone to disease. ..." ~ http://www.abc.net.au/news/stories/2009/10/05/2705473.htm http://www.abc.net.au/news/stories/2009/10/05/2705473.htm

stcredzero 16y ago
Also, mice do not suppress their telomerase. Without telomerase, tumors have a hard time getting larger than a golf ball. This is why large mammals like humans actually suppress telomerase expression in most cells. We might survive a golf ball sized tumor. A mouse? No way! There's no value in a mouse suppressing telomerase, so they're designed to have it switched on all the time. Would we want our telomerase to be switched on all the time? This would probably make us abnormally prone to developing cancer. This is also why whalers find tumor scars in whales all the time, but never run across whales that are going die of cancer. It's hard for a tumor to get larger than the size of your head. For us, this would likely be fatal. For a whale, it's no big deal.
- ShardPhoenix 16y ago
  While you probably wouldn't want full-on telomerase in your 20s might be worth the risk if you're pushing 80 :).
  - stcredzero 16y ago
    While you probably wouldn't want full-on telomerase in your 20s might be worth the risk if you're pushing 80 :). Actually, you are much more at risk for cancer in your 80's. That might be the worst possible plan. There are 7 distinct classes of damage that comprise the wear and tear resulting from aging. Addressing telomeres only addresses one of these. Read and learn: http://www.scribd.com/doc/522716/Aubrey-de-Grey-SENS http://www.scribd.com/doc/522716/Aubrey-de-Grey-SENS http://www.sens.org/ http://www.sens.org/
    - ShardPhoenix 16y ago
      My point is that you're probably going to die soon anyway, so even with the cancer risk the treatment may well be +EV. Similar to how people are more willing to undergo risky medical treatments when they're already dying.
- TheEzEzz 16y ago
  That is an interesting trade off. Still good new though, in my opinion. Cancer seems much more tractable than aging. If we can reduce the problem of aging to something that only requires us to additionally solve cancer, I would be ecstatic.
  - siganakis 16y ago
    One of the things that cancer is good at is switching "on" telomerase (enabling the cancer to spread), so naturally working out how to switch "off" telomerase in cancer tumors has actually been one of the key vectors in cancer research.
  - stcredzero 16y ago
    Cancer and aging are really the same problem. If we solve the other 6 forms of molecular damage and dysfunction, but don't solve the problem of cancer, then we all just get to be healthy for about a century, as if we're in our prime, but then die horribly of cancer.
- kiba 16y ago
  If we shorten all the telomerase in our body to the point where cancers can't do much more than grow to beign side tumor, cancer is prevented from killing us ever. On the other hand, we must replace all our cells periodically with the same shorten telomerase.
  - stavrianos 16y ago
    careful here- I'm fairly certain there's more to cancer than just tumors.
    - SapphireSun 16y ago
      Well the major danger from what I understand is tumors metastasizing all over your body. On the other hand, certain special kind of gland cancers start over or under producing vital hormones (for instance tumors of the adrenal glands can induce massive doses of cortisol and/or adrenaline). That ain't so good for you.
sorbus 16y ago
The news is actually further down in the article: they've figured out the processes by which telomeres cause these effects.
martey 16y ago
I am (unfortunately) not a biologist, but the abstract of their paper in Nature [1] seems to suggest that their research is notable not because they discovered telomerase is related to ageing, but because they figured out why lack of telomerase causes cells to stop regenerating and organs to fail: We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1α and PGC-1β promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere–p53–PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction. [1]: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature09787.html http://www.nature.com/nature/journal/vaop/ncurrent/full/natu...
jforman 16y ago
This paper is significant because it finds a precise molecular mechanism whereby reduced telomere function affects organ health. From the article, "We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1α and PGC-1β promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere–p53–PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction." Physorg isn't the most reputable science journalism around (heh), but Nature is arguably the most prestigious journal for life science in the world, and everybody involved in the process of publishing this paper, and writing the News & Views article about it, is aware of Elizabeth Blackburn and telomere research. The more we know about the pathways involved, the more avenues we have for drug development.
mkramlich 16y ago
good point. but from the sound of it, this finding too will likely earn a Nobel. we're talking about something which is very likely a subset of what's going to either achieve immortality, or cure/prevent cancer, or do both!

mindcrime 16y ago

Interesting stuff. I know it's just a small step, but it makes you wonder if maybe good ole Ray Kurzweil is onto something with his talk about achieving immortality. Which leads to some interesting questions... if there was a drug available that would let you live to be hundreds or thousands of years old, barring accident, would you take it? What would be the effect on society if death were all but eliminated? Would our population quickly overrun the limits of Earth's resources? Thinking about this almost feels like an episode of The Twilight Zone.

thewordis 16y ago
Personally, I've been hearing all my life about the Serious Philosophical Issues posed by life extension, and my attitude has always been that I'm willing to grapple with those issues for as many centuries as it takes. -- Patrick Nielsen Hayden
Zak 16y ago
I'd take it without a second thought. I've talked to a number of people who wouldn't though, and I find that curious. Why would you choose death by aging if it was optional? Suicide by other means would still be available if you grew tired of life.
- mindcrime 16y ago
  I'm with you; but I can imagine a few reasons why people might not take it. Some really religious types might feel that it's "playing God" or somehow interfering with "God's plan for the world." Some really eco-focused types might feel that it's immoral to live that long and therefore consume even more natural resources. Some conspiracy nuts would assume it was part of a government plan to do $SOMETHING. And some people might just assume there would be some sort of unforeseen consequences. Still, I bet most people would take it, and pretty quick.
  - jerf 16y ago
    Stepping up one meta point, a lot of people aren't actually teling you what they want, they're just flashing various social signals. As you say, put the pill in their hands, and, well, don't leave any of your body parts between their hands and their mouths if you don't want a nice new red welt. Yes, there are some who would not for real, but one wonders how even they would feel five years in.

bluekeybox 16y ago

Don't see anything new in the press release. Everything it states has been known for several years at least. Wish there was a link to the original study, but all links are either advertisements or internal links. The harvard.edu on the bottom does no good. What is the point of such press releases?

hartror 16y ago
They even gave a Nobel prize for the basis of this work like a year or two back.

SoftwareMaven 16y ago

So is the "news" here that the telomeres are the root cause rather than a contributing cause? I'm not seeing anything else I didn't know.

reasonattlm 16y ago

The popular press pieces are, as usual, breathlessly overhyped. Some commentary on this: http://www.fightaging.org/archives/2011/02/another-proposed-link-between-short-telomeres-and-dysfunctional-mitochondria.php http://www.fightaging.org/archives/2011/02/another-proposed-... "it is certainly the case that damaged mitochondria and shortening telomeres are only two of the possible reasons we suffer age-related degeneration. Many of the other causes of aging involve a build up of varying forms of damaging waste product that the body cannot remove - mechanisms which are quite capable of causing disability and death on their own, telomere shortening or no telomere shortening. "That said, telomeres, mitochondria, and p53 are all large and healthy areas of research when it comes to the biology of aging. I imagine that anyone would be pleased to produce good evidence that might mechanically tie them all together, such that one or more are secondary effects rather than primary causes. From an economic perspective, we should all be hoping that some of our present candidates for the primary causes of aging turn out to be secondary effects - because then we don't have to devote any time towards developing repair biotechnologies to fix them. "On a closer reading of the new research, I have to say that it looks to me very much like an independent confirmation of discoveries from 2007 and 2008 relating to mitochondrial damage, telomere length, and the enzyme telomerase. In a nutshell, it may be that telomere shortening is entirely driven by mitochondrial dysfunction" Etc. Links to more in the post.

lincolnpark 16y ago

Oh no! singularity is playin itself out