You'll also find a good introduction to the modern "aging is damage" viewpoint in the SENS distillation of consensus positions from various per-disease research fields:
I find the life expectancy vs. heart rate graph very interesting. The human point is the only one that lies well off the line of correlation, and it's tempting to see the distance as a result of our technological achievements. In other words, we're the only animal to have pushed ourselves to the right of that line by being able to fix at least some of what goes wrong.
There is some question over correlation of resting metabolic rate and mitochondrial constituents as a correlation of species life span, but that is totally separate from considerations of variations in life span within a species.
There is another theory about this: older humans are not 100% useless, they provide wisdom and skills to the younger people. As such communities with (not a burden) elder people have an advantage. And this removes some of the selection shadow.
The more I read about aging, the more interested I become about the subject, especially after Google created Calico and after watching some talks by Aubrey de Grey.
Reversing aging seems like such a science fiction thing, but then you take a look at how things were 50 years ago and how things are right now and you realize that a lot of the things that seem impossible right now might very well be possible in 20, 30 or 50 years.
We are living in the midst of the early phases of a biotechnology revolution every bit as profound and transformative as the computing revolution from the 1970s on. It is less apparent than it might be to the average person in the street because (a) next to no-one really spends much time thinking about medical research unless they have to, which is a whole massive issue with our society in and of itself, (b) regulatory burdens on medical technology ensures that the clinic is 10-20 years behind the bounds of the possible in the labs. Medical tourism does its part to help keep that delay lower than it might, but it's still a huge burden, and a huge cost in life - especially now that the upward curve of progress is potentially so steep.
The potential to be able to treat aging and begin to bring it under medical control within the next 20 years - IF the right research fields begin to dominate the mainstream, IF the funding arises, IF the public wakes up and regards aging research in the same was as they regard cancer research - is very real. That is why people like me spend time and effort to bang the drum, conduct grassroots fundraisers, and support progress in SENS-like rejuvenation research focused on repair of the cellular and tissue damage thought to cause aging. For example, clearance of senescent cells, an approach which has just now reached the point of credible demonstrations in normal mice, but needs much more support to make it into the mainstream. Is Calico funding this? No, not yet, and they won't until it gets more support:
Advocates and the research community are making progress, great progress when you look at 2015 in comparison to the state of things in 2005, but we need more people to take the step, become philanthropists, and materially support this and other early-stage research with the aim of bringing medicine under medical control. That support really does make a difference.
Thank you for your answer and for supporting this research! I know it's very hard to do, especially with things in such a young state, but do you think you could provide any more information of where we might be in 10, 20 or 50 years?
How long until life-extending medical therapies are developed?
How long is a piece of string? Questions of time depend on questions of money. Over the past decade the rough estimates for a fully funded crash research program to realize SENS in mice as rapidly as possible have floated around $1-2 billion over ten to twenty years. It might cost less than that now, given the rapid advance of biotechnology, but not enormously less. Unfortunately SENS is nowhere near as well funded as this: the current budget for the SENS Research Foundation has only recently reached $5 million / year. So it will certainly take time to increase funding to the optimal levels of $100 million / year or more; this is a major undertaking involving the creation of many new major programs of medical research throughout the world. That in and of itself might require decades, and it is hard to estimate the pace of growth in the early stages of a new industry. Any number of small, happenstance choices made by today's investors and researchers might gain or lose years of future progress.
Meanwhile on the other side of the fence drug discovery programs are undertaken in search of ways to modestly slow aging. We know that it can take a decade and $1 billion to push a good drug candidate through validation and regulatory hurdles, all the way from early tests to clinical use. There are no good candidates at this time, but every sign that some may emerge in the next few years based on analogs to rapamycin. So it's not unreasonable to think that a first generation drug that might slightly slow aging in humans could emerge in the mid to late 2020s. Even at that point the research community may not be able to say whether it in fact actually slows aging in humans, however, versus definitively knowing that it produces positive changes in short-term measures of health.
A toolkit for producing true rejuvenation in humans will require a range of different therapies, each of which can repair or reverse one of the varied root causes of degenerative aging. Research is underway for all of these classes of therapy, but very slowly and with very little funding in some cases. The funding situation spans the gamut from that of the stem cell research community, where researchers are afloat in money and interest, to the search for ways to break down advanced glycation endproducts (AGEs), which is a funding desert by comparison, little known or appreciated outside the small scientific community that works in that field.
While bearing in mind that progress in projects with little funding is unpredictable in comparison to that of well-funded projects, I think that we can still take a stab at a likely order of arrival for various important therapies needed to reverse aging. Thus an incomplete list follows, running from the earliest to the latest arrival, with the caveat that it is based on the present funding and publicity situation. If any one of the weakly funded and unappreciated lines of research suddenly became popular and awash with resources, it would probably move up in the ordering:
1) Destruction of Senescent Cells
Destroying specific cells without harming surrounding cells is a well-funded line of research thanks to the cancer community, and the technology platforms under development can be adapted to target any type of cell once it is understood how to target its distinctive features.
The research community has already demonstrated benefits from senescent cell destruction, and there are research groups working on this problem from a number of angles. A method of targeting senescent cells for destruction was recently published, and we can expect to see more diverse attempts at this in the next few years. As soon as one of these can be shown to produce benefits in mice that are similar to the early demonstrations, then senescent cell clearance becomes a going concern: something to be lifted from the deadlocked US regulatory process and hopefully developed quickly into a therapy in Asia, accessed via medical tourism.
2) Selective Pruning and Support of the Immune System
One of the reasons for immune system decline is crowding out of useful immune cells by memory immune cells that serve little useful purpose. Here, targeted cell destruction can also produce benefits, and early technology demonstrations support this view. Again, the vital component is the array of mechanisms needed to target the various forms of immune cell that must be pruned. I expect the same rising tide of technology and knowledge that enables senescent cell targeting will lead to the arrival of immune cell targeting on much the same schedule.
Culling the immune system will likely have to be supported with some form of repopulation of cells. It is already possible to repopulate a patient's immune system with immune cells cultivated from their own tissues, as demonstrated by the limited number of full immune system reboots carried out to cure autoimmune disorders. Alternatives to this process include some form of tissue engineering to recreate the dynamic, youthful thymus as a source of immune cells - or more adventurous processes such as cultivating thymic cells in a patient's lymph nodes.
3) Mitochondrial Repair
Our mitochondria sabotage us. There's a flaw in their structure and operation that causes a small but steadily increasing fraction of our cells to descend into a malfunctioning state that is destructive to bodily tissues and systems.
There are any number of proposed methods for dealing with this component of the aging process - either repairing or making it irrelevant - and a couple are in that precarious state of being just a little more solidity and work away from the point at which they could begin clinical development. The diversity of potential approaches in increasing too. Practical methods are now showing up for ways to put new mitochondria into cells, or target arbitrar...
The immune system operates more or less as a limited capacity system. It has low levels of replacement of immune cells in old age. For reasons that may have to do with exposure to persistent herpesviruses there is an expansion of memory cells and related types at the expense of the naive T cells needed to deal with new threats.
So the quick and dirty solution to this, which has some support from animal studies in the past few years, is to selectively kill off the undesirable excess memory cells. Perhaps via one of the targeted cell killing technologies developed in the cancer research community. This should free up capacity and spur the generation of more naive T cells to replace the lost numbers. It isn't a reality yet, but all the pieces are more or less in place. Someone just needs to do it.
A similar thing was demonstrated for B cell destruction in mice (innate immunity, not adaptive immunity): the bad cells were stripped out, and fresh new cells were generated as a result, and the innate immune response improved.
Regeneration and regrowth should be in situ where possible. Stem cell treatments are clearly beneficial, but will most likely give way to other methods of directly altering the behavior of native cells. Delivering signal molecules into the environment, or small molecules capable of otherwise adjusting cell epigenetic state.
In the final analysis if you can repair other forms of damage, many of the issues with regeneration should go away, as lost healing capacity is a result of age-related stem cell decline that it is in turn largely a reaction to a damaged environment. This of course needs to be proved. The best way to prove it is to implement the damage repair biotechnologies, see what happens.
Currently the major research focus in the mainstream is not to repair damage at all. It is rather to identify changes in signals and reverse them, and thus wake up stem cells and put them back to work on tissue maintenance, even damaged as they are and damaged as the tissue environment is. This is actually producing far better results with far less cancer as a result than you might think it would, which is always a bonus, but it isn't what I would consider the best path ahead.
Replacement of stem cell populations in the old are probably a necessary treatment. Clear out all damaged cells and generate a set of replacement cells from the patient's own tissues. Do that and then the organs should sort themselves out, except for gross damage that might need more treatment to rescue, such as deformation of the cardiovascular system as a result of hypertension that probably won't reverse itself.
The stem cell research field is on a collision course with the issue of stem cell aging. Most of the medical conditions that are best suited to regenerative medicine, tissue engineering, and similar cell based therapies are age-related, and thus most of the patients are old. In order for therapies to work well, there must be ways to work around the issues caused by the aged biochemistry of the patient. To achieve this end, the research community will essentially have to enumerate the mechanisms by which stem cell populations decline and fail with age, and then reverse their effects.
Where stem cells themselves are damaged by age, stem cell populations will have to be replaced. This is already possible for many different types of stem cell, but there are potentially hundreds of different types of adult stem cell - and it is too much to expect for the processes and biochemistry to be very similar in all cases. A great deal of work will remain to be accomplished here even after the first triumphs involving hearts, livers, and kidneys.
Much of the problem, however, is not the stem cells but rather the environment they operate within. This is the bigger challenge: picking out all the threads of signalling, epigenetic change, and cause and effect that leads to quieted and diminished stem cell populations - and the resulting frailty as tissues are increasingly poorly supported. This is a fair sized task, and little more than inroads have been made to date - a few demonstrations in which one stem cell type has been coerced into acting with youthful vigor, and a range of research on possible processes and mechanisms to explain how an aging metabolism causes stem cells to slow down and stop their work.
The stem cell research community is, however, one of the largest in the world, and very well funded. This is a problem that they have to solve on the way to their declared goals. What I would expect to see here is for a range of intermediary stopgap solutions to emerge in the laboratory and early trials over the next decade. These will be limited ways to invigorate a few aged stem cell populations, intended to be used to boost the effectiveness of stem cell therapies for diseases of aging.
Any more complete or comprehensive solution for stem cell aging seems like a longer-term prospect, given that it involves many different stem cell populations with very different characteristics.
5) Clearing Advanced Glycation Endproducts (AGEs)
AGEs cause inflammation and other sorts of mischief through their presence, and this builds up with age. Unfortunately, research on breaking down AGEs to remove their contribution to degenerative aging has been a very thin thread indeed over the past few decades: next to no-one works on it, despite its importance, and very little funding is devoted to this research.
Now on the one hand it seems to be the case that one particular type of AGE - glucosepane - makes up 90% or more the AGEs in human tissues. On the other hand, efforts to find a safe way to break it down haven't made any progress in the past decade, though a new initiative was launched comparatively recently. This is an excellent example of how minimally funded research can be frustrating: a field can hover just that one, single advance away from largely solving a major problem for years on end. All it takes is the one breakthrough, but the chances of that occurring depend heavily on the resources put into the problem: how many parallel lines of investigation can be followed, how many researchers are working away at it.
This is an excellent candidate for a line of research that could move upward in the order of arrival if either a large source of funding emerged or a plausible compound was demonstrated to safely and aggressively break down glucospane in cell cultures. There is far less work to be done here than to reverse stem cell aging, for example.
6) Clearing Aggregates and Lysomal Garbage
All sorts of aggregates build up within and around cells as a result of normal metabolic proces...
SENS and SENS-like work outside the area of cancer and stem cell research is generally at the pre-animal-testing stage, so not something you can run via the ITP.
Senescent cell clearance is there, so could be making in that direction in the years ahead. Nothing moves fast of course.
I'm not sure where the ITP stands on things like stem cell treatments. They are very focused on diet, drugs, supplements, and resulting complex changes in the operation of normal metabolism. i.e. things that don't matter if you want meaningful results in extended healthy life. Good for scientific rigor though, going back through all the studies in the past that failed to control for inadvertent calorie restriction and showing that they were wrong.
Well, they don't allow interventions that require daily injections, etc, but the implication seems to be that something that requires a once-a-month injection, such as senescent cell clearance, would likely be allowed. Some of the "senolytics" are small molecules as well (Jim Kirkland's work, for example).
Actually the ITP is not just interested in metabolism. They do hormones and anti-inflammatories as well. But I don't get the impression that they're solely focused on those things: anyone who can make a good case for a non-labor-intensive intervention can get in. That's why I asked if SENS has applied to the ITP: because I know they have some different ideas than academia, but I'd like to know more about specific interventions they've proposed or tested.
Are you by chance going to the AAA meeting in Marina del Rey in a few weeks? I'd buy you a beer there and we could continue the conversation then ;)
Actually, they do age like you age, obviously so for the car and the device where it is a matter of breakage of components, and for the wine and the cheese more a matter of drawing analogies with specific biochemical processes involved in aging.
Reliability theory applies very well to aging, just as it does to the aging of machinery, and its high level models reproduce reality quite well:
At the bottom, it's all an increase in entropy. That's my standard answer, probably informed by my college studies (Physics, not CS).
The layers on top might be different, but at the very bottom of things, it's always entropy "trying" to increase. That's why computers eventually break, that's why living things age and die.
To counteract this tendency, you'd have to somehow prevent the entropic increase within each system. Technically doable, but the devil is in the details. Life itself fights entropy, the problem is that whatever anti-entropic mechanisms it employs, they're not stable long-term, at least not for pluricellular organisms as separate systems. The biosphere as a whole has actually been remarkably resilient so far.
I've posted about some of the interesting stuff going on regarding stem cells, particularly around hockey legend Gordie Howe's rather miraculous recover from a stroke earlier this year. I'm really not sure why this isn't getting more news nationally, or even why on HN it isn't getting any traction/discussion:
That's my original post yesterday for this story. No discussion or interest/upvote.
So is it simply that the average HN'er is around 28 years old and just doesn't care about aging or stem cell research that is mostly aimed at fixing 'old people'? Is everyone just assuming this stuff will get sorted out in the next 20 years by time the average HN'er actually needs to worry about it?
Or is it because the stem cell medical centers that provided Mr. Howe with the treatments are outside the US? Aka, not invented here so must be BS?
It's puzzling, I mean we all have parents that are aging and having gone through watching a parent lose a lot of their capabilities from a stroke last year (and eventually dying from the strokes fallout a few months later), all I can say is this stuff can become front and center to your personal interest very rapidly when it hits home.
"That's my original post yesterday for this story. No discussion or interest/upvote."
The surface area of HN is so broad, the number of readers interested in pretty low. This is a observable problem. I often see lots of votes and zero responses for interesting posts.
Interesting enough to click, glance over, but not enough to think about and comment.
I love this article! The author points out that as lifespan goes up the effect of aging on fitness goes down. So provided that an organism lives long enough, aging is not penalized by Natural Selection.
I'm happy to report that scientists have been seriously testing if stuff actually works for over a century (Slonaker, 1912).
They typically try an intervention, like diet or exercise, on lab animals, and then see how long they live.
For what it's worth, I maintain the world's biggest spread sheet of these life span experiments.
It summarizes over 14,000.
One column is the intervention (diet, exercise, etc..) another is the change in lifespan (+10%, -2%, etc...) another is the species (human, mice, etc...) and so on.
The most interesting part is that a relatively simple medical procedure called plasmapheresis or plasma exchange, might be used for rejuvenation. The process would be to exchange the blood plasma of an old person with that of a young person many times over a period of time.
The blood plasma contains signaling molecules and there is strong evidence that some of them are used to synchronize the current age throughout the body, perhaps to a master clock somewhere. This causes telomeres to be shortened, DNA repair mechanisms to be turned off, stem cells to stop dividing etc. If the clock could be reset with young plasma, the stem cells would be reset to a young state and can start dividing again to regenerate tissue. Experiments on rats suggests this is indeed happening and a number of academic labs and even a startup called alkahest is now working on getting this tested in humans.
37 comments
[ 2.9 ms ] story [ 76.3 ms ] threadhttp://senescence.info/aging_theories.html
You'll also find a good introduction to the modern "aging is damage" viewpoint in the SENS distillation of consensus positions from various per-disease research fields:
http://sens.org/research/introduction-to-sens-research
That is one synthesis of which damage is primary and important. Another is the Hallmarks of Aging:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/
Is it enough for us to consider lower heart rate as an ideal value to optimize? Obviously being in better shape and see often correlated.
http://en.wikipedia.org/wiki/Rate_of_living_theory
There is some question over correlation of resting metabolic rate and mitochondrial constituents as a correlation of species life span, but that is totally separate from considerations of variations in life span within a species.
http://dx.doi.org/10.1089/rej.2008.0676
Nonetheless, resting metabolic rate does seem to predict human longevity:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100751/
Interestingly the Palo Alto Longevity Prize is using heart rate variability as a metric to optimize in mammals:
http://paloaltoprize.com/
Reversing aging seems like such a science fiction thing, but then you take a look at how things were 50 years ago and how things are right now and you realize that a lot of the things that seem impossible right now might very well be possible in 20, 30 or 50 years.
The potential to be able to treat aging and begin to bring it under medical control within the next 20 years - IF the right research fields begin to dominate the mainstream, IF the funding arises, IF the public wakes up and regards aging research in the same was as they regard cancer research - is very real. That is why people like me spend time and effort to bang the drum, conduct grassroots fundraisers, and support progress in SENS-like rejuvenation research focused on repair of the cellular and tissue damage thought to cause aging. For example, clearance of senescent cells, an approach which has just now reached the point of credible demonstrations in normal mice, but needs much more support to make it into the mainstream. Is Calico funding this? No, not yet, and they won't until it gets more support:
http://www.scripps.edu/news/press/2015/20150309agingcell.htm...
Advocates and the research community are making progress, great progress when you look at 2015 in comparison to the state of things in 2005, but we need more people to take the step, become philanthropists, and materially support this and other early-stage research with the aim of bringing medicine under medical control. That support really does make a difference.
----------
How long until life-extending medical therapies are developed?
How long is a piece of string? Questions of time depend on questions of money. Over the past decade the rough estimates for a fully funded crash research program to realize SENS in mice as rapidly as possible have floated around $1-2 billion over ten to twenty years. It might cost less than that now, given the rapid advance of biotechnology, but not enormously less. Unfortunately SENS is nowhere near as well funded as this: the current budget for the SENS Research Foundation has only recently reached $5 million / year. So it will certainly take time to increase funding to the optimal levels of $100 million / year or more; this is a major undertaking involving the creation of many new major programs of medical research throughout the world. That in and of itself might require decades, and it is hard to estimate the pace of growth in the early stages of a new industry. Any number of small, happenstance choices made by today's investors and researchers might gain or lose years of future progress.
Meanwhile on the other side of the fence drug discovery programs are undertaken in search of ways to modestly slow aging. We know that it can take a decade and $1 billion to push a good drug candidate through validation and regulatory hurdles, all the way from early tests to clinical use. There are no good candidates at this time, but every sign that some may emerge in the next few years based on analogs to rapamycin. So it's not unreasonable to think that a first generation drug that might slightly slow aging in humans could emerge in the mid to late 2020s. Even at that point the research community may not be able to say whether it in fact actually slows aging in humans, however, versus definitively knowing that it produces positive changes in short-term measures of health.
----------
While bearing in mind that progress in projects with little funding is unpredictable in comparison to that of well-funded projects, I think that we can still take a stab at a likely order of arrival for various important therapies needed to reverse aging. Thus an incomplete list follows, running from the earliest to the latest arrival, with the caveat that it is based on the present funding and publicity situation. If any one of the weakly funded and unappreciated lines of research suddenly became popular and awash with resources, it would probably move up in the ordering:
1) Destruction of Senescent Cells
Destroying specific cells without harming surrounding cells is a well-funded line of research thanks to the cancer community, and the technology platforms under development can be adapted to target any type of cell once it is understood how to target its distinctive features.
The research community has already demonstrated benefits from senescent cell destruction, and there are research groups working on this problem from a number of angles. A method of targeting senescent cells for destruction was recently published, and we can expect to see more diverse attempts at this in the next few years. As soon as one of these can be shown to produce benefits in mice that are similar to the early demonstrations, then senescent cell clearance becomes a going concern: something to be lifted from the deadlocked US regulatory process and hopefully developed quickly into a therapy in Asia, accessed via medical tourism.
2) Selective Pruning and Support of the Immune System
One of the reasons for immune system decline is crowding out of useful immune cells by memory immune cells that serve little useful purpose. Here, targeted cell destruction can also produce benefits, and early technology demonstrations support this view. Again, the vital component is the array of mechanisms needed to target the various forms of immune cell that must be pruned. I expect the same rising tide of technology and knowledge that enables senescent cell targeting will lead to the arrival of immune cell targeting on much the same schedule.
Culling the immune system will likely have to be supported with some form of repopulation of cells. It is already possible to repopulate a patient's immune system with immune cells cultivated from their own tissues, as demonstrated by the limited number of full immune system reboots carried out to cure autoimmune disorders. Alternatives to this process include some form of tissue engineering to recreate the dynamic, youthful thymus as a source of immune cells - or more adventurous processes such as cultivating thymic cells in a patient's lymph nodes.
3) Mitochondrial Repair
Our mitochondria sabotage us. There's a flaw in their structure and operation that causes a small but steadily increasing fraction of our cells to descend into a malfunctioning state that is destructive to bodily tissues and systems.
There are any number of proposed methods for dealing with this component of the aging process - either repairing or making it irrelevant - and a couple are in that precarious state of being just a little more solidity and work away from the point at which they could begin clinical development. The diversity of potential approaches in increasing too. Practical methods are now showing up for ways to put new mitochondria into cells, or target arbitrar...
I don't understand what you're saying about pruning the immune system. What is that trying to fix? What goes wrong with the immune system as it ages?
So the quick and dirty solution to this, which has some support from animal studies in the past few years, is to selectively kill off the undesirable excess memory cells. Perhaps via one of the targeted cell killing technologies developed in the cancer research community. This should free up capacity and spur the generation of more naive T cells to replace the lost numbers. It isn't a reality yet, but all the pieces are more or less in place. Someone just needs to do it.
A similar thing was demonstrated for B cell destruction in mice (innate immunity, not adaptive immunity): the bad cells were stripped out, and fresh new cells were generated as a result, and the innate immune response improved.
In the final analysis if you can repair other forms of damage, many of the issues with regeneration should go away, as lost healing capacity is a result of age-related stem cell decline that it is in turn largely a reaction to a damaged environment. This of course needs to be proved. The best way to prove it is to implement the damage repair biotechnologies, see what happens.
Currently the major research focus in the mainstream is not to repair damage at all. It is rather to identify changes in signals and reverse them, and thus wake up stem cells and put them back to work on tissue maintenance, even damaged as they are and damaged as the tissue environment is. This is actually producing far better results with far less cancer as a result than you might think it would, which is always a bonus, but it isn't what I would consider the best path ahead.
Replacement of stem cell populations in the old are probably a necessary treatment. Clear out all damaged cells and generate a set of replacement cells from the patient's own tissues. Do that and then the organs should sort themselves out, except for gross damage that might need more treatment to rescue, such as deformation of the cardiovascular system as a result of hypertension that probably won't reverse itself.
The stem cell research field is on a collision course with the issue of stem cell aging. Most of the medical conditions that are best suited to regenerative medicine, tissue engineering, and similar cell based therapies are age-related, and thus most of the patients are old. In order for therapies to work well, there must be ways to work around the issues caused by the aged biochemistry of the patient. To achieve this end, the research community will essentially have to enumerate the mechanisms by which stem cell populations decline and fail with age, and then reverse their effects.
Where stem cells themselves are damaged by age, stem cell populations will have to be replaced. This is already possible for many different types of stem cell, but there are potentially hundreds of different types of adult stem cell - and it is too much to expect for the processes and biochemistry to be very similar in all cases. A great deal of work will remain to be accomplished here even after the first triumphs involving hearts, livers, and kidneys.
Much of the problem, however, is not the stem cells but rather the environment they operate within. This is the bigger challenge: picking out all the threads of signalling, epigenetic change, and cause and effect that leads to quieted and diminished stem cell populations - and the resulting frailty as tissues are increasingly poorly supported. This is a fair sized task, and little more than inroads have been made to date - a few demonstrations in which one stem cell type has been coerced into acting with youthful vigor, and a range of research on possible processes and mechanisms to explain how an aging metabolism causes stem cells to slow down and stop their work.
The stem cell research community is, however, one of the largest in the world, and very well funded. This is a problem that they have to solve on the way to their declared goals. What I would expect to see here is for a range of intermediary stopgap solutions to emerge in the laboratory and early trials over the next decade. These will be limited ways to invigorate a few aged stem cell populations, intended to be used to boost the effectiveness of stem cell therapies for diseases of aging.
Any more complete or comprehensive solution for stem cell aging seems like a longer-term prospect, given that it involves many different stem cell populations with very different characteristics.
5) Clearing Advanced Glycation Endproducts (AGEs)
AGEs cause inflammation and other sorts of mischief through their presence, and this builds up with age. Unfortunately, research on breaking down AGEs to remove their contribution to degenerative aging has been a very thin thread indeed over the past few decades: next to no-one works on it, despite its importance, and very little funding is devoted to this research.
Now on the one hand it seems to be the case that one particular type of AGE - glucosepane - makes up 90% or more the AGEs in human tissues. On the other hand, efforts to find a safe way to break it down haven't made any progress in the past decade, though a new initiative was launched comparatively recently. This is an excellent example of how minimally funded research can be frustrating: a field can hover just that one, single advance away from largely solving a major problem for years on end. All it takes is the one breakthrough, but the chances of that occurring depend heavily on the resources put into the problem: how many parallel lines of investigation can be followed, how many researchers are working away at it.
This is an excellent candidate for a line of research that could move upward in the order of arrival if either a large source of funding emerged or a plausible compound was demonstrated to safely and aggressively break down glucospane in cell cultures. There is far less work to be done here than to reverse stem cell aging, for example.
6) Clearing Aggregates and Lysomal Garbage
All sorts of aggregates build up within and around cells as a result of normal metabolic proces...
Senescent cell clearance is there, so could be making in that direction in the years ahead. Nothing moves fast of course.
I'm not sure where the ITP stands on things like stem cell treatments. They are very focused on diet, drugs, supplements, and resulting complex changes in the operation of normal metabolism. i.e. things that don't matter if you want meaningful results in extended healthy life. Good for scientific rigor though, going back through all the studies in the past that failed to control for inadvertent calorie restriction and showing that they were wrong.
Actually the ITP is not just interested in metabolism. They do hormones and anti-inflammatories as well. But I don't get the impression that they're solely focused on those things: anyone who can make a good case for a non-labor-intensive intervention can get in. That's why I asked if SENS has applied to the ITP: because I know they have some different ideas than academia, but I'd like to know more about specific interventions they've proposed or tested.
Are you by chance going to the AAA meeting in Marina del Rey in a few weeks? I'd buy you a beer there and we could continue the conversation then ;)
Actually, no. Those things don't 'age' like you age.
BTW, trying to answer existentialist questions with biological theories is futile.
You could not answer the question "why does plague decimates us", until you could answer "it does not" and the question left the horizon.
Reliability theory applies very well to aging, just as it does to the aging of machinery, and its high level models reproduce reality quite well:
http://en.wikipedia.org/wiki/Reliability_theory
http://en.wikipedia.org/wiki/Reliability_theory_of_aging_and...
The layers on top might be different, but at the very bottom of things, it's always entropy "trying" to increase. That's why computers eventually break, that's why living things age and die.
To counteract this tendency, you'd have to somehow prevent the entropic increase within each system. Technically doable, but the devil is in the details. Life itself fights entropy, the problem is that whatever anti-entropic mechanisms it employs, they're not stable long-term, at least not for pluricellular organisms as separate systems. The biosphere as a whole has actually been remarkably resilient so far.
I've posted about some of the interesting stuff going on regarding stem cells, particularly around hockey legend Gordie Howe's rather miraculous recover from a stroke earlier this year. I'm really not sure why this isn't getting more news nationally, or even why on HN it isn't getting any traction/discussion:
http://www.freep.com/story/sports/nhl/red-wings/2015/05/18/g...
So is it simply that the average HN'er is around 28 years old and just doesn't care about aging or stem cell research that is mostly aimed at fixing 'old people'? Is everyone just assuming this stuff will get sorted out in the next 20 years by time the average HN'er actually needs to worry about it?
Or is it because the stem cell medical centers that provided Mr. Howe with the treatments are outside the US? Aka, not invented here so must be BS?
It's puzzling, I mean we all have parents that are aging and having gone through watching a parent lose a lot of their capabilities from a stroke last year (and eventually dying from the strokes fallout a few months later), all I can say is this stuff can become front and center to your personal interest very rapidly when it hits home.
The surface area of HN is so broad, the number of readers interested in pretty low. This is a observable problem. I often see lots of votes and zero responses for interesting posts.
Interesting enough to click, glance over, but not enough to think about and comment.
I'm happy to report that scientists have been seriously testing if stuff actually works for over a century (Slonaker, 1912).
They typically try an intervention, like diet or exercise, on lab animals, and then see how long they live.
For what it's worth, I maintain the world's biggest spread sheet of these life span experiments.
It summarizes over 14,000.
One column is the intervention (diet, exercise, etc..) another is the change in lifespan (+10%, -2%, etc...) another is the species (human, mice, etc...) and so on.
It's interesting to see what works.
More info is at
http://morse.kiwi.nz/kingsley/doku.php?id=science:start
http://protein.bio.msu.ru/biokhimiya/contents/v78/pdf/bcm_10...
The most interesting part is that a relatively simple medical procedure called plasmapheresis or plasma exchange, might be used for rejuvenation. The process would be to exchange the blood plasma of an old person with that of a young person many times over a period of time.
The blood plasma contains signaling molecules and there is strong evidence that some of them are used to synchronize the current age throughout the body, perhaps to a master clock somewhere. This causes telomeres to be shortened, DNA repair mechanisms to be turned off, stem cells to stop dividing etc. If the clock could be reset with young plasma, the stem cells would be reset to a young state and can start dividing again to regenerate tissue. Experiments on rats suggests this is indeed happening and a number of academic labs and even a startup called alkahest is now working on getting this tested in humans.