Telomeres are repeating sequences of nucleic acids that cap the ends of chromosomes in the cell nucleus and stop actual gene-coding DNA from being chopped off when a cell divides. The mechanisms of DNA replication require extra leg room at the ends of the strand, a trailing sequence that is not copied over to the new strand under assembly - and the primary role of telomeres is to be the part that is dropped on the floor. A little of their length is thus lost with every cell division. This shortening acts as a clock to count cell divisions, and cells with very short telomeres stop replicating - they either enter cellular senescence (which ideally then causes the immune system to destroy them) or destroy themselves directly via programmed cell death mechanisms.
Telomere length is more dynamic than this simple picture, however. In some cell populations, such as the various types of stem cell that maintain tissues and produce new cells to replace those lost or damaged, an enzyme called telomerase continually lengthens telomeres so as to allow a cell lineage to continue dividing indefinitely.
Ordinary, non-stem cell populations exhibit a range of telomere lengths, some short, some long. You might imagine that a population of cells replenished more frequently or recently by stem cells will have longer telomeres on average. A population that is receiving less support might have shorter telomeres. Researchers have shown that a higher proportion of short telomeres in white blood cells correlates well with ill health or stress, and somewhat correlates with age. Some more complex measures of telomere length, a step above just taking the average, have been shown to correlate well with age, however, and other techniques do a fair job of predicting future life expectancy in laboratory animals.
A few years back a brace of startup biotech companies were aiming to address aspects of aging by lengthening telomeres through the use of telomerase. None of that went anywhere, unfortunately, but it's possible that they were just too early - it is frequently the case that all of the first batch of companies in a new area of biotechnology fail. It's a tough business to be in. I was a skeptic at the time regarding their potential for success based on my expectation that telomere length will prove not to be a root cause of aging. It looks a lot more like a marker for (a consequence of) some of the responses to the root causes of aging, in particular the reduction in stem cell activity that is characteristic of old age.
Nonetheless, researchers are demonstrating extension of life in mice through telomerase these days, but it is as yet unknown as to exactly why this works. Perhaps it makes stem cells work harder to maintain tissues, perhaps there is just one critically limiting type of stem cell or tissue that benefits from more telomerase, or perhaps it involves other effects causes by increased levels of telomerase that have nothing to do with telomere length. It is worth bearing in mind that there are considerable differences in natural levels of telomerase and the resulting telomere dynamics between mice and people, however. Telomerase therapy is probably not something you'd want to just up and try without the research community first obtaining a much greater understanding of why it works to extend life in mice.
Why? Well, the risk of telomere lengthening in humans is cancer. Any mechanism that globally, or possibly even narrowly, extends telomere length in people will raise the risk of suffering cancer. The whole system of telomere dynamics and cellular senescence is intimately tied to the processes of cancer suppression, while all cancers evolve ways of lengthening their telomeres to allow unlimited cell division. Boosting your telomerase levels looks a lot more risky to me than, say, undergoing first generation stem cell transplants.
There continues to be a lot of activity in telomere research and development. The present brace of telomere-related biotech startups are commercializing ways to measure telomere leng...
Unfortunately, this "problem" was already solved a long time ago... by cancer cells ! [1]
It turns out that having immortal cells (by either avoiding death signals or by having "enhanced" replicative machinery is a great way to develop cancerous cells. So you have to carefully regulate the lifetime of the cell... which is what telomere are doing in the first place.
Right. Furthermore, our cells have many of other mechanism besides telomeres whose function is to prohibit immortality in a way that's difficult to bypass. (If it were easy to bypass, then it would be less effective at suppressing cancer.)
Of which the one with Cynthia Kenyon is also interesting, particularly as a contrast on fundamental philosophy and strategy in the approach to treating aging as a medical condition:
Aubrey de Grey is the cofounder of the SENS Research Foundation and coordinator of rejuvenation research programs. Cynthia Kenyon worked on single gene manipulations that extend nematode longevity back in the 1990s, efforts that arguably kicked off the modern wave of interest in slowing aging.
In these two short interviews you can see illustrated the most important division in the modern work aimed at intervention into the aging process: on the one hand the mainstream approach of altering the operation of metabolism so as to slow down aging, based on traditional drug discovery methodologies, and on the other hand the radical, disruptive approach of repairing the damage caused by the normal operation of metabolism, requiring the development of new biotechnologies. The strategy here is to avoid changing the operation of metabolism, because that is very hard and far too little is known of the important details, but rather periodically clean up the consequences of normal metabolic activity in order to prevent that damage from overwhelming and altering biological systems so as to cause degenerative aging.
I'm greatly in favor of the latter approach because all the signs suggest it should be far more efficient and effective at extending healthy life spans, not to mention producing actual rejuvenation in the old. You can't greatly help the old by slowing down aging: better technologies are needed. Rejuvenation is needed. You can't bring aging under medical control by working on metabolic alteration to slow aging. Repair is needed, not merely dialing down the pace of new damage.
This is me reading between the lines -- so maybe not the parent commenter meant at all! -- but I think the point is that all sorts of grudges, prejudices, and regrets naturally expire through generational turnover, and in a world without aging that natural expiration won't be there to help society put the past behind us.
The loss of grudges/prejudices is also a loss of skills and unique perspectives. That sounds as much an opportunity as a danger.
I could come up with ridiculous 'nightmares', and interpret them, as well:
I wake from nightmare worlds where 'world hunger' is cured but 'satiety' becomes broken.
Interpreted as:
Without scarcity peoples' greed will continue to grow unabated. The lust for consumption will result with the depletion of natural resources, and the destruction of society.
The dream is a non sequitur; and even taken as a metaphor, it has gapping holes in the logic!
1. Prejudices are passed down through generations.
2. People change their position on subjects, when new information becomes available.
3. There's nothing 'natural' about living short lives. Some species live longer than us; and some are even negligibly senescent[0]!
4. I've established there's at least one other mechanism by which people can alter their ideas (point 2). Others could be found.
5. Dying of cancer (and other diseases) seems like the worst possible solution to the problem. Torturing people who don't age, and then not have them die in the end seems more humane! (That may be the second worst solution). Killing healthy 150 y/o, so that there's generational turnover would also work (I would prefer that to the status quo, personally). Under such circumstance, I think it probable a reasonable remedy could be found (sans death, pain, and indignity)!
Thanks for the interpretation, but you may have been overly charitable!
Its a cause of death. We like to avoid those. And we know multicellular organisms exist that can maintain their telomeres and avoid senescence.
We are almost certainly going to be able to genetically engineer that into future people at some point, among a lot of other useful things. Dunno if we are going to manage to get gene therapy that can alter living humans so drastically before they die, though. And who knows when it will happen, just that it almost certainly will, unless we blow ourselves up.
This is not strictly true; aging is much like having AIDS -- it lets actual causes of death come in and kill you. Nobody ever died (directly) of AIDS, and nobody's ever died of old age either.
Sometimes I feel we should cure living. I would prefer to live only 70 years but fully, having built good human relationships, knowing how to learn, rather than 100 unfulfilled ones.
Most young people, including myself, do tend to think they would like to live until X years of age. Getting to know some older people, though, it's interesting how we tend to see things differently when we live that many years. I know quite a few people in their late 60s and I think they have Many good years left to enjoy their hard-earned retirement, watch their kids and grandkids grow up, or is some cases continue to do great work.
Ha, I hope I didn't sound like I rejected being 'old' or ageist. I too grew up[1] to be very fond of people of any age and love their perspective and experiences (or lack thereof)[2]. Nor to take away people opportunity to enjoy their closed ones. But I've seen many times broken lives out of misunderstandings that weren't related to biology or aging. When you're almost unable to relate to your family or couldn't build one, you have other things to improve rather than aging.
[1] although very late, maybe on average it's a coming of age thing.
[2] being into computer and technology, I think we have a special relationship to fads, newness, communication and history that makes us (at least I) interested in others in weird ways. How people managed to solve problems or live in a different context, what was the same, what really changed for them as a human.
Which can be decomposed into not taking the cure by choice (suicide) and being deprived of it forcibly, which can be further decomposed into negligence (accident) or malice (murder).
I doubt it will be awkward. It will be viewed that aging is a disease, that we have the cure now, so there's one less way to die. Getting rid of polio didn't make the other ways of dieing more awkward.
There is also a slow dissolution into a different state of being.
I imagine humans living long enough to begin augmenting their bodies and brains into a thing that no longer resembles the original being. Or even a form of life as we understand it today.
Would have profound impact on how we value our own lives (and others). If you are 60 you might get a motorcycle because what the hell. Worse case you crash and lose 20-30 years of which only 10-15 are good. With aging out out the window you could have centuries to lose.
In a way, we've already "cured" aging. On average, we live a lot longer than many of our ancestors. We can check many diseases and conditions that would normally kill elderly people. The problem is like cancer, in that it's not one thing, but a multitude of things. (And cancer itself is among that multitude!)
Not many people, outside of healthcare workers and AIDS patients know of cytomegalovirus, but most of the population has it. What most people don't know, is that if we could otherwise have a life expectancy of 200 years, many of us would be dying from cytomegalovirus. (Simplified version: it takes up memory slots in our immune system, but at a slow enough rate, we die of other causes before that can happen.)
I suspect that "curing" aging will consist of extending the average lifespan a decade at a time, as we cure dozens of different conditions. Something as complex as a human body is always going to have some unforeseeable epiphenomenal mode of failure, given enough time. We know from thermodynamics and the Halting Problem that everything is bound to break down, and that we won't be able to predict all of the ways it can happen.
(For a given degree of complexity in any turing complete mechanism, maybe an overwhelmingly correct heuristic for the halting problem is a piece of paper with the word "Yes" printed on it.)
Thermodynamics doesn't say that "everything is bound to break down, and that we won't be able to predict all of the ways it can happen".
I guess you're referring to the second law of thermodynamics. It says that the entropy of the universe tends to increase. This is predictable and the lack of "negentropy" won't be an issue for a long time. The heat death of the universe is supposed to be on the order 10^100 years from now, so is not very relevant when talking about curing aging.
I suspect they were referring to the ways our body is part of numerous pseudo-closed local systems, and in each of those systems entropy will tend to increase. It's true that we are also open systems in meaningful ways and can be farmers of enthalpy inside our bodies. To some extent that's exactly what life is--enthalpy farming equipment. But farming is tricky and requires constant energy inputs. And it does seem like fighting the entropy of those pseudo-closed (ie can be opened with effort) systems is a difficult if not losing battle.
Thermodynamics doesn't say that "everything is bound to break down,
It's pretty close to that.
and that we won't be able to predict all of the ways it can happen".
So either you don't understand how to generalize the Halting Problem, or you didn't get the reference.
I guess you're referring to the second law of thermodynamics. It says that the entropy of the universe tends to increase.
Exactly. There are far more states of a given machine that are broken than there are states of a given machine that "work."
EDIT: Also, to expand on what erikpukinskis says in the cousin comment, you can enthalpy farm to fix what's wrong in any given body. The problem is knowing what to fix. The body is so vastly complex, it's going to be very hard to guarantee we always know what to fix ahead of time for everybody. (Halting Problem) Hence, some small fraction of any population is always going to be dying from unforeseen failure modes, unless some philosophically interesting tinkering takes place. (In any case, it's inevitable that all Homo sapiens will be gone, eventually.)
We're now learning how to "reset" the immune system.
1. Collect immune system "seed' cells.
2. Wipe out the existing immune system with chemo therapy drugs and other violence.
3. Inject the collected cells and let them build a new fresh immune system.
You now have lost all your immunities and will need to be revaccinated for everything. But any autoimmune disease like MS you had is probably also gone.
> I suspect that "curing" aging will consist of extending the average lifespan a decade at a time, as we cure dozens of different conditions. Something as complex as a human body is always going to have some unforeseeable epiphenomenal mode of failure, given enough time.
There's a very foreseeable failure mode that this approach doesn't address at all.
Who'd win in a fight: a 150-pound 25-year-old guy or a 170-pound 75-year-old guy?
If you think the answer is "the 25-year-old", you've noticed a problem with aging that slowly extending lifespans doesn't solve. It's not just about whether you're alive or dead.
If you think the answer is "the 25-year-old", you've noticed a problem with aging that slowly extending lifespans doesn't solve. It's not just about whether you're alive or dead.
Apparently you are not familiar with the SENS arguments for how an immortal human would have the apparent age of ~35.
Considering how little progress we've made, I hardly think that our lifespans are the primary limiters in that venture. I mean you can travel to Mars in 8 months-3 years, yet we haven't.
Energy is our primary limitation right now. We have nuclear but are too afraid of launching large quantities of the raw materials into atmosphere in case of a catastrophic failure (and showering land OR sea with some heavy radioactive metal).
We also have fossil fuels which are very energy dense, but still heavy/expensive. And finally we have solar which has been a long-term popular form of spacecraft energy, but it doesn't provide enough to travel between planets YET.
Ultimately if we invented "infinite safe energy" tomorrow I don't see Mars or greater space exploration as being too big of a challenge. In particular as getting stuff into atmosphere is now energy-free, and your only limit is the cost of the raw materials.
I doubt that life-span would make much of a difference, and I would even suspect that overall, development would slow down with a longer life span even without aging of body and brain, as the 'caste of the old and powerful' will defend their old ways and suppress new radical ideas coming from the young, which will be in an even bigger minority then today. Just imagine what the world would look like if Stalin would still be alive, or if the government of East Germany wouldn't have entirely consisted of senile old fogeys, the iron curtain would very likely still be up.
One reason why we age and die - might be because we(any living being) want to evolve, and that pressurizes us to cross breed and give birth to new generation before we die and finally die and not hog up all the resources ourselves. And let the better generation live on.
That natural strategy might have become suboptimal since the progress in science.
No no, cause would be something like length of telomere being short or something. The reason (evolutionary reason) would be that nature needs to clear the previous generation in order to make room for a newer and better generation.
Evolution doesn't work like that. You don't consider newer generations 'better', you consider the survivors better. So you're assuming your conclusion and burying it in human moral terms, which evolution has no obligation to apply.
Didn't know about this guy (Aubrey de Grey) but googling for him I just learnt that's he's 52.. From that vid I thought he was a sleep-deprived 30-something!
54 comments
[ 4.4 ms ] story [ 110 ms ] threadI was impressed by this study[2]: "Lifestyle Changes May Lengthen Telomeres, A Measure of Cell Aging".
[1] http://en.wikipedia.org/wiki/Telomere
[2] http://www.ucsf.edu/news/2013/09/108886/lifestyle-changes-ma...
Telomere length is more dynamic than this simple picture, however. In some cell populations, such as the various types of stem cell that maintain tissues and produce new cells to replace those lost or damaged, an enzyme called telomerase continually lengthens telomeres so as to allow a cell lineage to continue dividing indefinitely.
Ordinary, non-stem cell populations exhibit a range of telomere lengths, some short, some long. You might imagine that a population of cells replenished more frequently or recently by stem cells will have longer telomeres on average. A population that is receiving less support might have shorter telomeres. Researchers have shown that a higher proportion of short telomeres in white blood cells correlates well with ill health or stress, and somewhat correlates with age. Some more complex measures of telomere length, a step above just taking the average, have been shown to correlate well with age, however, and other techniques do a fair job of predicting future life expectancy in laboratory animals.
A few years back a brace of startup biotech companies were aiming to address aspects of aging by lengthening telomeres through the use of telomerase. None of that went anywhere, unfortunately, but it's possible that they were just too early - it is frequently the case that all of the first batch of companies in a new area of biotechnology fail. It's a tough business to be in. I was a skeptic at the time regarding their potential for success based on my expectation that telomere length will prove not to be a root cause of aging. It looks a lot more like a marker for (a consequence of) some of the responses to the root causes of aging, in particular the reduction in stem cell activity that is characteristic of old age.
Nonetheless, researchers are demonstrating extension of life in mice through telomerase these days, but it is as yet unknown as to exactly why this works. Perhaps it makes stem cells work harder to maintain tissues, perhaps there is just one critically limiting type of stem cell or tissue that benefits from more telomerase, or perhaps it involves other effects causes by increased levels of telomerase that have nothing to do with telomere length. It is worth bearing in mind that there are considerable differences in natural levels of telomerase and the resulting telomere dynamics between mice and people, however. Telomerase therapy is probably not something you'd want to just up and try without the research community first obtaining a much greater understanding of why it works to extend life in mice.
Why? Well, the risk of telomere lengthening in humans is cancer. Any mechanism that globally, or possibly even narrowly, extends telomere length in people will raise the risk of suffering cancer. The whole system of telomere dynamics and cellular senescence is intimately tied to the processes of cancer suppression, while all cancers evolve ways of lengthening their telomeres to allow unlimited cell division. Boosting your telomerase levels looks a lot more risky to me than, say, undergoing first generation stem cell transplants.
There continues to be a lot of activity in telomere research and development. The present brace of telomere-related biotech startups are commercializing ways to measure telomere leng...
It turns out that having immortal cells (by either avoiding death signals or by having "enhanced" replicative machinery is a great way to develop cancerous cells. So you have to carefully regulate the lifetime of the cell... which is what telomere are doing in the first place.
[1] Many many sources, but for instance the "Enabling Replicative Immortality" of Hanahan&Weinberg 2011, "The Hallmarks of Cancer: the next generation" http://www.sciencedirect.com/science/article/pii/S0092867411...
http://www.npr.org/templates/transcript/transcript.php?story...
"Things that have only a 50 percent chance of happening in 20 years from now are supposed to sound like science fiction."
This interview with de Grey is one part of a longer piece with other interviews:
http://www.npr.org/programs/ted-radio-hour/408023272/the-fou...
Of which the one with Cynthia Kenyon is also interesting, particularly as a contrast on fundamental philosophy and strategy in the approach to treating aging as a medical condition:
http://www.npr.org/templates/transcript/transcript.php?story...
---
Aubrey de Grey is the cofounder of the SENS Research Foundation and coordinator of rejuvenation research programs. Cynthia Kenyon worked on single gene manipulations that extend nematode longevity back in the 1990s, efforts that arguably kicked off the modern wave of interest in slowing aging.
In these two short interviews you can see illustrated the most important division in the modern work aimed at intervention into the aging process: on the one hand the mainstream approach of altering the operation of metabolism so as to slow down aging, based on traditional drug discovery methodologies, and on the other hand the radical, disruptive approach of repairing the damage caused by the normal operation of metabolism, requiring the development of new biotechnologies. The strategy here is to avoid changing the operation of metabolism, because that is very hard and far too little is known of the important details, but rather periodically clean up the consequences of normal metabolic activity in order to prevent that damage from overwhelming and altering biological systems so as to cause degenerative aging.
I'm greatly in favor of the latter approach because all the signs suggest it should be far more efficient and effective at extending healthy life spans, not to mention producing actual rejuvenation in the old. You can't greatly help the old by slowing down aging: better technologies are needed. Rejuvenation is needed. You can't bring aging under medical control by working on metabolic alteration to slow aging. Repair is needed, not merely dialing down the pace of new damage.
I could come up with ridiculous 'nightmares', and interpret them, as well:
I wake from nightmare worlds where 'world hunger' is cured but 'satiety' becomes broken.
Interpreted as:
Without scarcity peoples' greed will continue to grow unabated. The lust for consumption will result with the depletion of natural resources, and the destruction of society.
The dream is a non sequitur; and even taken as a metaphor, it has gapping holes in the logic!
1. Prejudices are passed down through generations.
2. People change their position on subjects, when new information becomes available.
3. There's nothing 'natural' about living short lives. Some species live longer than us; and some are even negligibly senescent[0]!
4. I've established there's at least one other mechanism by which people can alter their ideas (point 2). Others could be found.
5. Dying of cancer (and other diseases) seems like the worst possible solution to the problem. Torturing people who don't age, and then not have them die in the end seems more humane! (That may be the second worst solution). Killing healthy 150 y/o, so that there's generational turnover would also work (I would prefer that to the status quo, personally). Under such circumstance, I think it probable a reasonable remedy could be found (sans death, pain, and indignity)!
Thanks for the interpretation, but you may have been overly charitable!
---
[0] http://en.wikipedia.org/wiki/Negligible_senescence
We are almost certainly going to be able to genetically engineer that into future people at some point, among a lot of other useful things. Dunno if we are going to manage to get gene therapy that can alter living humans so drastically before they die, though. And who knows when it will happen, just that it almost certainly will, unless we blow ourselves up.
> [It's] a cause of death.
This is not strictly true; aging is much like having AIDS -- it lets actual causes of death come in and kill you. Nobody ever died (directly) of AIDS, and nobody's ever died of old age either.
Thousand years later, first colonists in a different galaxy:
- Remember that dude from our childhood?
- Yeah, choosing to live a mere 70 years - so weird...
- Never mind, let's keep Terra-forming..."
[1] although very late, maybe on average it's a coming of age thing.
[2] being into computer and technology, I think we have a special relationship to fads, newness, communication and history that makes us (at least I) interested in others in weird ways. How people managed to solve problems or live in a different context, what was the same, what really changed for them as a human.
I doubt it will be awkward. It will be viewed that aging is a disease, that we have the cure now, so there's one less way to die. Getting rid of polio didn't make the other ways of dieing more awkward.
I imagine humans living long enough to begin augmenting their bodies and brains into a thing that no longer resembles the original being. Or even a form of life as we understand it today.
Investing in things other than not-freaking-dying - now that's awkward.
Not many people, outside of healthcare workers and AIDS patients know of cytomegalovirus, but most of the population has it. What most people don't know, is that if we could otherwise have a life expectancy of 200 years, many of us would be dying from cytomegalovirus. (Simplified version: it takes up memory slots in our immune system, but at a slow enough rate, we die of other causes before that can happen.)
I suspect that "curing" aging will consist of extending the average lifespan a decade at a time, as we cure dozens of different conditions. Something as complex as a human body is always going to have some unforeseeable epiphenomenal mode of failure, given enough time. We know from thermodynamics and the Halting Problem that everything is bound to break down, and that we won't be able to predict all of the ways it can happen.
(For a given degree of complexity in any turing complete mechanism, maybe an overwhelmingly correct heuristic for the halting problem is a piece of paper with the word "Yes" printed on it.)
I guess you're referring to the second law of thermodynamics. It says that the entropy of the universe tends to increase. This is predictable and the lack of "negentropy" won't be an issue for a long time. The heat death of the universe is supposed to be on the order 10^100 years from now, so is not very relevant when talking about curing aging.
It's pretty close to that.
and that we won't be able to predict all of the ways it can happen".
So either you don't understand how to generalize the Halting Problem, or you didn't get the reference.
I guess you're referring to the second law of thermodynamics. It says that the entropy of the universe tends to increase.
Exactly. There are far more states of a given machine that are broken than there are states of a given machine that "work."
EDIT: Also, to expand on what erikpukinskis says in the cousin comment, you can enthalpy farm to fix what's wrong in any given body. The problem is knowing what to fix. The body is so vastly complex, it's going to be very hard to guarantee we always know what to fix ahead of time for everybody. (Halting Problem) Hence, some small fraction of any population is always going to be dying from unforeseen failure modes, unless some philosophically interesting tinkering takes place. (In any case, it's inevitable that all Homo sapiens will be gone, eventually.)
1. Collect immune system "seed' cells.
2. Wipe out the existing immune system with chemo therapy drugs and other violence.
3. Inject the collected cells and let them build a new fresh immune system.
You now have lost all your immunities and will need to be revaccinated for everything. But any autoimmune disease like MS you had is probably also gone.
http://www.nih.gov/researchmatters/january2015/01122015reset...
There's a very foreseeable failure mode that this approach doesn't address at all.
Who'd win in a fight: a 150-pound 25-year-old guy or a 170-pound 75-year-old guy?
If you think the answer is "the 25-year-old", you've noticed a problem with aging that slowly extending lifespans doesn't solve. It's not just about whether you're alive or dead.
Apparently you are not familiar with the SENS arguments for how an immortal human would have the apparent age of ~35.
Energy is our primary limitation right now. We have nuclear but are too afraid of launching large quantities of the raw materials into atmosphere in case of a catastrophic failure (and showering land OR sea with some heavy radioactive metal).
We also have fossil fuels which are very energy dense, but still heavy/expensive. And finally we have solar which has been a long-term popular form of spacecraft energy, but it doesn't provide enough to travel between planets YET.
Ultimately if we invented "infinite safe energy" tomorrow I don't see Mars or greater space exploration as being too big of a challenge. In particular as getting stuff into atmosphere is now energy-free, and your only limit is the cost of the raw materials.
That natural strategy might have become suboptimal since the progress in science.