Root molecular cause of declining health in the old found by scientists | Hacker News Reader

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

physorg.com

45 pointsbootload45 comments

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

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.

While you probably wouldn't want full-on telomerase in your 20s might be worth the risk if you're pushing 80 :).

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.sens.org/

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.

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.

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.

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.

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.

careful here- I'm fairly certain there's more to cancer than just tumors.

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.

The news is actually further down in the article: they've figured out the processes by which telomeres cause these effects.

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/natu...

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.

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!

The popular press pieces are, as usual, breathlessly overhyped. Some commentary on this:

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.

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?

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

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.

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.

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.

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.

I've noticed that often people who say they wouldn't want to live forever are those who have no long-term grandiose goals that they feel are personally achievable given enough time (e.g. become a billionaire, live on Mars, create the next Google, etc.).

I've heard that there is a big longevity community in the valley.

Talk's cheap if you're not faced with such a choice.

Cognitive dissonance. You can either live knowing and regretting that you're going to die one day, of you can find reasons to believe it's not a bad thing. In time, you can come to actually prefer things this way.

Read and learn: http://www.sens.org/

Also: http://methuselahfoundation.com/

And donate if you can. I believe they have the best expected benefit per dollar of any cause.

Depends on your values and your expectations. If you do time discounting, you can save more lives sooner by donating to VillageReach or the Stop TB Partnership. If you think human civilization might have some trouble negotiation the next few thousand years, an existential risk reduction charity like FHI or SIAI might be better.

If neither of those applies, and you think SENS has a good chance of achieving their goal with sufficient funding, go for it!

Absolutely. My 8 year-old has been asking a lot of questions and expressing concerns about death lately. In an effort to reassure him, at one point I explained to him that the pace of scientific discovery is accelerating rapidly and that there's a good chance that by the time he's older people will be able to live as long as they want.

A few nights ago he says, out of the blue, "Dad, if they do invent some medicine that let's people live forever, I hope they do it before you die."

"Me too", I said.

That's actually a very cute story. It would make a nice blog post, or Calvin & Hobbes type comic strip or something.

Pretty soon having children would require a license, and eugenics would make a violent comeback.

The initial phase would probably be that you only need a license if you are on the pills most likely.

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?

Of course, and the vast majority of those who say no actually would if given the opportunity.

What would be the effect on society if death were all but eliminated?

Greatly reduced medical costs and increased productivity and quality of life, for starters. The one negative is that we'd probably have to limit childbirth for a few decades while space colonization gets going, but that's a comparatively small price to pay.

A cure for aging terrifies me, my gut tells me that it would be the end of homo sapiens.

Think about it, do you really think all higher order life has this "defect" for no reason? Without aging, the youth would be at an eternal disadvantage in society. The rush to have children would all but disappear without a biological clock. Evolutionarily speaking, a cure for aging is a dead end.

That said, i could easily see it happening, so like I said, I'm terrified.

I think by the point that we can banish aging technological self-improvement will have overtaken evolution by a long way. We already severely handicap evolution by using medicine to compensate for disadvantageous features such as short-sigtedness.

We just alter the criteria for selection. Evolution is still there.

In general, anything that happens after childbirth is tertiary from an evolutionary standpoint. All higher-order life has this defect not necessarily because it's good, but because merely delaying expression of the defect is enough. But what satisfies natural selection in the general case is not necessarily the best choice for people.

Also, humans have become so dominant by leapfrogging biological evolution with our technological evolution. This would just be one more example. It would not really be a dead-end unless we're looking at some eugenics angle.

Higher order life has this "defect" because, from an evolutionary perspective, there is little reason for us to stick around for very long after reproducing. After passing our genes on to our children we have some years where it is helpful for their survival that we are still alive, but pretty soon Darwin has no more use for you.

The various problems that you imagine might result from curing ageing can be solved _after_ we solve the problem of hundreds of thousands of people dying every single day.

The entire point of a civilized society is to overcome evolution. For consistency, do you at least hate all our technology that lets e.g. babies that would have died 50 years ago lead long productive lives? They obviously had bad genes, right?

Being terrified of change is an evolutionary dead end. At a talk Leonard Nimoy gave at USC on his poetry he remarked that his garden had taught him that one could learn to value the change in in a thing over the current state of that thing. I found that to be a fairly profound statement and worth remembering.

The claim that youth would be at an eternal disadvantage in an ageless world not supported by observations in the current world. If having more time conferred universal advantage then youth today could not compete with those older than them. This is clearly not the case and demonstrated by young entreprenuers every day.

To the extent that the cellular processes active in creative, contemplative, and evaluative thinking are exposed, if it becomes common to unify those processes in the functioning of everyone's consciousness then it is possible it would give rise to a modest time advantage for those who had been thinking longer about the same things.

The more I read the news, the more I appreciate watching The Twighlight Zone :-)

The solution would be to limit reproduction, something we should be considering even with the current population size. China is on the right track I think, if they'd only pursue it with an incentivised system rather than law.

I'd do anything to live forever in any capacity. Even just to watch, how could it ever get boring?

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

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.

Oh no! singularity is playin itself out

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