A recent NYT book review: In his new book, “Long for This World,” Weiner makes similar use of another brilliant theoretical scientist, the English gerontologist Aubrey de Grey, a tireless proselytizer for radical life extension. … The inspiration for de Grey’s scientific quest for immortality came in a flash one sleepless night: “What these [aging] troubles all have in common is that they fill the aging body with junk. Maybe we can just clean up all the scree and rubble that gathers in our aging bodies.” The beauty of this view is that “curing” aging requires no special knowledge of design, or any understanding of just how the cellular junk got there in the first place. It only requires that we get rid of it. As de Grey sees it, there are seven types of cellular junk. … De Grey’s dream of conquering death may seem far-fetched and unreal, but Big Pharma is already at work on some of these ideas. …
Jonathan Weiners book was a great read on the beach at Long Beach in California. It is a first class introduction to the subject and a stress free read. As far as aging itself there are various routes being pursued that will eventually achieve the goal of radical life extension. Personally I am very confident that the SENS project will come to fruition and that Aubrey de Grey is very much on the right track. The compelling piece of proof to support Aubrey’s theory is that our risk of dying doubles every 8 years although there is some argument as to whether this is every 7, 8 or 9 years, regardless lets call it 8 and take as an example the fact that your risk of death within a year at age 14 is 1 in 2000 but it increases exponentially so that at 22 it is double what it was at 14 and at 30 double what it was at 22. This doubling every eight years does not become a major problem until you reach early middle age because it starts off at such a low level but the rate of increase is exponential as opposed to linear so it accelerates rapidly with increasing age. What is abundantly clear is that the only likely cause for this increasing risk of mortality is the accumulation of junk in the body and the genetic damage to our DNA which builds up over time. Aubrey's theory that if we intervened and removed some of the damage we would make a person biologically younger certainly makes sense. The vital thing is that If it were to turn out that the Aubrey de Grey theory was wrong (or partially wrong) or that we had overlooked something vital then great promise is still beckoning as he acknowledges himself via other breakthroughs in biotechnology and nanotechnology. I am confident that the biotec revolution will yield significant increases in lifespan regardless, the key factor is that Aubrey's role is vital because he is the catalyst that is driving things forward and encouraging people in unrelated fields to work together. I cover quite a lot of areas regarding Aubrey de Grey and other people and organisations involved in combating aging on one of my websites at http://drjohnty.com/ In ending I have to say that the thing that never fails to amaze me is Aubrey's focus and determination to succeed. Personally I feel that if anyone can pull scientists together from all these different areas of research and end up saving 100,000 lives per day it is Dr Aubrey de Grey. You can check out the latest information at http://www.sens.org/
For indefinite lifespan, you have to cure cancer, heart disease, Alzheimer’s, and damage to non-repairing tissues like ligaments, among many other problems.
I believe Aubrey de Grey has provided a likely cure for cancer as part of snes.
Heart disease should not be a problem (Scientists discover new method for regenerating heart muscle by direct reprogramming A strategy to fix a broken heart Also search for "total artificial heart")
Damage to non-reparing tissue is a mute point if they are able to repair a heart (it's super non-reparing itself). About here I'll also throw in stemcell research wich can be used to repair "non-repairing tissues".
Different animals have different lifespans. I think a rat lives 2 years. I have a dog 17 years old. He is old and will soon die. A human also has a certain lifespan. It looks like this is about 85 or 90. Illness can shorten lifespan aging is not prevented by eliminating disease . I don't think anyone's theories explain the different lifespans. Aging may be programed. Perhaps telomere length is part of it. Semi starvation can extend life some but is it worth it? From an evolutionary point of view , there just doesn't seem to be any reason for 20 year old rats, 90 year old dogs or 500 year old humans. We are probably supposed to die and have mechanisms to assure this.
Theres an understandable misunderstanding going around. Those that support the movement for indefinite life extension that use the word immortality are generally either mispeaking, or they think that everybody else gets that they really mean biological immortality. In general though, it is true, it is best to avoid confusion by avoiding the word Immortality. I work at the Immortality Institute. The name was created back in the day when the cause was still brand spanking new and naive in many regards as it built itself. We are now in the process of creating a second name for the organization. "Immortality Institute" may remain for iconic reasons, it may catch on in the same way that we know that Amazon.com is not about a river, or it may phase out. All in all, in the end, nobody thinks we are going to become like the highlanders and the greek gods, we all work for indefinite life extension. Interesting article youve written here. I hope this clears some things up.
Luke, one of the reasons that teenagers take risks is because the have the capacity to tolerate more damage because they are still young. If you want to live forever, you can't tolerate any damage because all damage is (to some extent) cumulative.
I think that transitions in NO levels are what modulate various life stages and program things like the utility function. When you are young and have a high NO level, you can afford to be reckless because you have a high capacity for repair. After that capacity is degraded, the level of ROS goes up, the NO level goes down, and the human utility function is skewed to a more risk-averse mind set.
Fixing the damage is a lot higher degree of difficulty (by many orders of magnitude) than preventing the damage from happening in the first place. I think you can slow the rate of damage down a lot simply by increasing NO levels. This is what people are trying to do by taking antioxidants (even if they don't realize it) because a high ROS state is necessarily a low NO state and it is low NO that triggers most of the degenerative pathways (not ROS). A high NO state is what you want and is not the same as a low ROS state (but a high NO state is always a low ROS state). Low ROS doesn't give you the high NO signaling pathways you need to turn on repair and keep it at a high level. Once you start to get damage, that shows up as increased ROS which lowers NO levels.
"Extending life indefinitely will require changing the control paradigm of ATP allocation and the human utility function so that a near death metabolic state is not euphoric. When that is done, a risk of death won’t produce a thrill of euphoria."
You seem to have skipped a few logical steps there... Repairing the body such that it is exactly like an 18 year old would mean restoring whatever it is that makes an 18 year old take risks (and makes them better able to escape risky situations).
If I hear you right you're saying the simplest life extension method is to reconfigure the ATP control mechanism somehow. I don't know enough cellular biology to usefully critique that, but it sounds to me like one of many possible approaches you could take to curing aging. Even if you are right, it doesn't seem like it would need to apply indefinitely -- only until we figure out how to fix it so we are like 18 year olds again.
Things that feel enjoyable are not necessarily good for us in the long term (or even short term). Auto-erotic asphyxiation is practiced because it is enjoyable, even though it carries a high risk of death. Similarly self-injected drug users will use needles they know are likely infected with fatal diseases.
My hypothesis is that the utility function of humans depends on their metabolic state, and that a state of near death metabolic stress induces a state of euphoria. I think this evolved so that organisms would be able to run themselves to death while escaping from a predator.
Organisms can run themselves to death. To be caught by a predator is near certain death, any damage short of death is acceptable if it allows escape from a predator. To allow an organism to run itself to death, a state of euphoria must be induced by physiology. My hypothesis is that the euphoria of near death metabolic stress is the final common pathway of the euphoria of autoerotic asphyxiation, of stimulant drugs of abuse, the runner's high, the euphoria of drowning, solvent huffing, and the near death experience of “going toward the light”.
People running marathons do exhibit cardiac damage following the race. Overuse injury is not uncommon because people in a high aerobic metabolic output state are not always cognizant of the damage they are doing to their bodies. This state is necessary to escape from a predator. You can't stop because you are tired, or because your muscles hurt when you are being chased by a bear. You can only stop after you have escaped, or when you are forced to stop because your muscles have necrosed, after you have depleted their ATP supply trying to escape.
Extending life indefinitely will require changing the control paradigm of ATP allocation and the human utility function so that a near death metabolic state is not euphoric. When that is done, a risk of death won't produce a thrill of euphoria.
Immortality is long. Really long. You just won't believe how vastly hugely mindbogglingly long it is. I mean you may think it's a long time until the next millennium, but that's just peanuts to immortality!
A typical post from someone who doesn't understand what indefinite life extension means. Does your grandmother have the body of a 27 year old? I'm making the assumption here that she doesn't want to live because she has the body of an 87 year old, hence your comment. If she did have the body of a 27 year old things might be different.
Luke, cells are doing that all the time. If you want to do something counter to the normal control system, you have to over-ride the normal control system, or it will seek to counter what you are trying to do.
For example this is the problem with trying to use supplemental antioxidants to reduce oxidative stress. It doesn't work long term. A state of oxidative stress is a powerful control parameter. Cells use that to change their physiology into a different metabolic state so to accomplish different things. Stress is a state of oxidative stress because a state of oxidative stress triggers compensatory pathways to deal with the stress. When there is insufficient ATP, cells trigger oxidative stress to increase ATP production rates and to turn off non-essential ATP consuming pathways. This is what happens during ischemic preconditioning. Oxidative stress triggers ischemic preconditioning largely by lowering the basal NO level (what I am doing research is on). An important pathway is disinhibitiion of cytochrome c oxidase to maximize reduction of O2, to maximize aerobic ATP production (something you will probably need if you are under stress). NO inhibits the binding of O2 to cytochrome c oxidase, to increase O2 reduction, that NO must be removed. That is what the superoxide that mitochondria produce does, that superoxide is a necessary control parameter to regulate mitochondria O2 reduction.
Every large, long term, placebo controlled double blind study of supplemental antioxidants has shown no benefit. Most show slight detriment effects of supplemental antioxidants. I think that is because the supplemental antioxidants are in excess of what physiology needs to regulate the state of oxidative stress it is trying to achieve. Physiology has unlimited capacity to generate superoxide and so destroy excess antioxidants. Free radicals are extremely important signaling molecules which physiology uses for many life-critical signaling pathways. Using free radicals as signaling molecules requires the proper background of antioxidants. Increasing the background may not be compatible with what physiology is trying to do. I think the observed slight decrement in health associated with supplemental antioxidants is from physiology generating more free radicals to destroy the excess antioxidants.
I think a major control parameter of the balance between turning on repair and turning off repair to save ATP is the state of oxidative stress. High oxidative stress is necessarily a low NO state, and many of the effects of oxidative stress are mediated by low NO. High NO raises ATP levels and (I think) upregulates repair pathways. I think that is why NO levels are higher during sleep, to periodically upregulate repair during times of low ATP demand by other pathways. Essentially all the disorders that are made worse by stress are also characterized by insomnia, and are also disorders of degeneration. I think they all have a final common pathway of low basal NO.
No one can imagine living forever. 87 is not much older than 18 in terms of forever. As Robin has said, living literally forever is simply not the topic of conversation. Replace the term "forever" with a specific number like "1000 years" and it just doesn't make sense. Who specifically doesn't want to live 1000 years? Or a hundred for that matter?
If you are going to argue that living longer while your body breaks down from aging is undesirable, please bear in mind that that is not what anyone has actually suggested. It's not even plausible; the longer you spend in an elderly condition, the more likely you are to die. The only way to live longer is to restore a person's youth.
My condolences on your mother's condition. It is not reversible with current technology, but if she is given cryonic stabilization I see no reason to doubt that she might one day be cured of her aging and other illnesses. The cellular damage of aging is not greater then the cellular damage of cryonic preservation. Immense progress needs to be made to reverse both kinds of damage, but that's no reason to think it won't happen ever.
Why not? He said "It seems to me most likely", implying the "absolutely unavoidable" is a statement of qualified belief in a hard physical limit, not a statement of absolute confidence.
This is flawed in two ways, however. OKCupid, as a dating site, is heavily driven by appearances, and to a lesser extent, writing ability. The two factors that make men the most attractive to women, in my experience- confidence and income- are not a factor on OKCupid, as openly advertising your income is frowned upon in American society, and confidence can't really be determined from a written profile. Yet both of these factors are generally higher in men over 30. Many men I know didn't find that women were very attracted to them until they were around 35+, established in their careers and making significant amounts of money.
likewise, in some cultures, older men are considered more attractive than younger ones, not only for financial reasons, but due to cultural perceptions and beliefs. This is especially true in Asia, where younger women frequently date and marry significantly older men who are not necessarily "rich".
Jonathan Weiners book was a great read on the beach at Long Beach in California. It is a first class introduction to the subject and a stress free read. As far as aging itself there are various routes being pursued that will eventually achieve the goal of radical life extension. Personally I am very confident that the SENS project will come to fruition and that Aubrey de Grey is very much on the right track. The compelling piece of proof to support Aubrey’s theory is that our risk of dying doubles every 8 years although there is some argument as to whether this is every 7, 8 or 9 years, regardless lets call it 8 and take as an example the fact that your risk of death within a year at age 14 is 1 in 2000 but it increases exponentially so that at 22 it is double what it was at 14 and at 30 double what it was at 22. This doubling every eight years does not become a major problem until you reach early middle age because it starts off at such a low level but the rate of increase is exponential as opposed to linear so it accelerates rapidly with increasing age. What is abundantly clear is that the only likely cause for this increasing risk of mortality is the accumulation of junk in the body and the genetic damage to our DNA which builds up over time. Aubrey's theory that if we intervened and removed some of the damage we would make a person biologically younger certainly makes sense. The vital thing is that If it were to turn out that the Aubrey de Grey theory was wrong (or partially wrong) or that we had overlooked something vital then great promise is still beckoning as he acknowledges himself via other breakthroughs in biotechnology and nanotechnology. I am confident that the biotec revolution will yield significant increases in lifespan regardless, the key factor is that Aubrey's role is vital because he is the catalyst that is driving things forward and encouraging people in unrelated fields to work together. I cover quite a lot of areas regarding Aubrey de Grey and other people and organisations involved in combating aging on one of my websites at http://drjohnty.com/ In ending I have to say that the thing that never fails to amaze me is Aubrey's focus and determination to succeed. Personally I feel that if anyone can pull scientists together from all these different areas of research and end up saving 100,000 lives per day it is Dr Aubrey de Grey. You can check out the latest information at http://www.sens.org/
For indefinite lifespan, you have to cure cancer, heart disease, Alzheimer’s, and damage to non-repairing tissues like ligaments, among many other problems.
I believe Aubrey de Grey has provided a likely cure for cancer as part of snes.
Heart disease should not be a problem (Scientists discover new method for regenerating heart muscle by direct reprogramming A strategy to fix a broken heart Also search for "total artificial heart")
Damage to non-reparing tissue is a mute point if they are able to repair a heart (it's super non-reparing itself). About here I'll also throw in stemcell research wich can be used to repair "non-repairing tissues".
Different animals have different lifespans. I think a rat lives 2 years. I have a dog 17 years old. He is old and will soon die. A human also has a certain lifespan. It looks like this is about 85 or 90. Illness can shorten lifespan aging is not prevented by eliminating disease . I don't think anyone's theories explain the different lifespans. Aging may be programed. Perhaps telomere length is part of it. Semi starvation can extend life some but is it worth it? From an evolutionary point of view , there just doesn't seem to be any reason for 20 year old rats, 90 year old dogs or 500 year old humans. We are probably supposed to die and have mechanisms to assure this.
Theres an understandable misunderstanding going around. Those that support the movement for indefinite life extension that use the word immortality are generally either mispeaking, or they think that everybody else gets that they really mean biological immortality. In general though, it is true, it is best to avoid confusion by avoiding the word Immortality. I work at the Immortality Institute. The name was created back in the day when the cause was still brand spanking new and naive in many regards as it built itself. We are now in the process of creating a second name for the organization. "Immortality Institute" may remain for iconic reasons, it may catch on in the same way that we know that Amazon.com is not about a river, or it may phase out. All in all, in the end, nobody thinks we are going to become like the highlanders and the greek gods, we all work for indefinite life extension. Interesting article youve written here. I hope this clears some things up.
Luke, one of the reasons that teenagers take risks is because the have the capacity to tolerate more damage because they are still young. If you want to live forever, you can't tolerate any damage because all damage is (to some extent) cumulative.
I think that transitions in NO levels are what modulate various life stages and program things like the utility function. When you are young and have a high NO level, you can afford to be reckless because you have a high capacity for repair. After that capacity is degraded, the level of ROS goes up, the NO level goes down, and the human utility function is skewed to a more risk-averse mind set.
Fixing the damage is a lot higher degree of difficulty (by many orders of magnitude) than preventing the damage from happening in the first place. I think you can slow the rate of damage down a lot simply by increasing NO levels. This is what people are trying to do by taking antioxidants (even if they don't realize it) because a high ROS state is necessarily a low NO state and it is low NO that triggers most of the degenerative pathways (not ROS). A high NO state is what you want and is not the same as a low ROS state (but a high NO state is always a low ROS state). Low ROS doesn't give you the high NO signaling pathways you need to turn on repair and keep it at a high level. Once you start to get damage, that shows up as increased ROS which lowers NO levels.
"Extending life indefinitely will require changing the control paradigm of ATP allocation and the human utility function so that a near death metabolic state is not euphoric. When that is done, a risk of death won’t produce a thrill of euphoria."
You seem to have skipped a few logical steps there... Repairing the body such that it is exactly like an 18 year old would mean restoring whatever it is that makes an 18 year old take risks (and makes them better able to escape risky situations).
If I hear you right you're saying the simplest life extension method is to reconfigure the ATP control mechanism somehow. I don't know enough cellular biology to usefully critique that, but it sounds to me like one of many possible approaches you could take to curing aging. Even if you are right, it doesn't seem like it would need to apply indefinitely -- only until we figure out how to fix it so we are like 18 year olds again.
Things that feel enjoyable are not necessarily good for us in the long term (or even short term). Auto-erotic asphyxiation is practiced because it is enjoyable, even though it carries a high risk of death. Similarly self-injected drug users will use needles they know are likely infected with fatal diseases.
My hypothesis is that the utility function of humans depends on their metabolic state, and that a state of near death metabolic stress induces a state of euphoria. I think this evolved so that organisms would be able to run themselves to death while escaping from a predator.
Organisms can run themselves to death. To be caught by a predator is near certain death, any damage short of death is acceptable if it allows escape from a predator. To allow an organism to run itself to death, a state of euphoria must be induced by physiology. My hypothesis is that the euphoria of near death metabolic stress is the final common pathway of the euphoria of autoerotic asphyxiation, of stimulant drugs of abuse, the runner's high, the euphoria of drowning, solvent huffing, and the near death experience of “going toward the light”.
People running marathons do exhibit cardiac damage following the race. Overuse injury is not uncommon because people in a high aerobic metabolic output state are not always cognizant of the damage they are doing to their bodies. This state is necessary to escape from a predator. You can't stop because you are tired, or because your muscles hurt when you are being chased by a bear. You can only stop after you have escaped, or when you are forced to stop because your muscles have necrosed, after you have depleted their ATP supply trying to escape.
Extending life indefinitely will require changing the control paradigm of ATP allocation and the human utility function so that a near death metabolic state is not euphoric. When that is done, a risk of death won't produce a thrill of euphoria.
Immortality is long. Really long. You just won't believe how vastly hugely mindbogglingly long it is. I mean you may think it's a long time until the next millennium, but that's just peanuts to immortality!
A typical post from someone who doesn't understand what indefinite life extension means. Does your grandmother have the body of a 27 year old? I'm making the assumption here that she doesn't want to live because she has the body of an 87 year old, hence your comment. If she did have the body of a 27 year old things might be different.
Luke, cells are doing that all the time. If you want to do something counter to the normal control system, you have to over-ride the normal control system, or it will seek to counter what you are trying to do.
For example this is the problem with trying to use supplemental antioxidants to reduce oxidative stress. It doesn't work long term. A state of oxidative stress is a powerful control parameter. Cells use that to change their physiology into a different metabolic state so to accomplish different things. Stress is a state of oxidative stress because a state of oxidative stress triggers compensatory pathways to deal with the stress. When there is insufficient ATP, cells trigger oxidative stress to increase ATP production rates and to turn off non-essential ATP consuming pathways. This is what happens during ischemic preconditioning. Oxidative stress triggers ischemic preconditioning largely by lowering the basal NO level (what I am doing research is on). An important pathway is disinhibitiion of cytochrome c oxidase to maximize reduction of O2, to maximize aerobic ATP production (something you will probably need if you are under stress). NO inhibits the binding of O2 to cytochrome c oxidase, to increase O2 reduction, that NO must be removed. That is what the superoxide that mitochondria produce does, that superoxide is a necessary control parameter to regulate mitochondria O2 reduction.
Every large, long term, placebo controlled double blind study of supplemental antioxidants has shown no benefit. Most show slight detriment effects of supplemental antioxidants. I think that is because the supplemental antioxidants are in excess of what physiology needs to regulate the state of oxidative stress it is trying to achieve. Physiology has unlimited capacity to generate superoxide and so destroy excess antioxidants. Free radicals are extremely important signaling molecules which physiology uses for many life-critical signaling pathways. Using free radicals as signaling molecules requires the proper background of antioxidants. Increasing the background may not be compatible with what physiology is trying to do. I think the observed slight decrement in health associated with supplemental antioxidants is from physiology generating more free radicals to destroy the excess antioxidants.
I think a major control parameter of the balance between turning on repair and turning off repair to save ATP is the state of oxidative stress. High oxidative stress is necessarily a low NO state, and many of the effects of oxidative stress are mediated by low NO. High NO raises ATP levels and (I think) upregulates repair pathways. I think that is why NO levels are higher during sleep, to periodically upregulate repair during times of low ATP demand by other pathways. Essentially all the disorders that are made worse by stress are also characterized by insomnia, and are also disorders of degeneration. I think they all have a final common pathway of low basal NO.
"No one wants to live forever."
No one can imagine living forever. 87 is not much older than 18 in terms of forever. As Robin has said, living literally forever is simply not the topic of conversation. Replace the term "forever" with a specific number like "1000 years" and it just doesn't make sense. Who specifically doesn't want to live 1000 years? Or a hundred for that matter?
If you are going to argue that living longer while your body breaks down from aging is undesirable, please bear in mind that that is not what anyone has actually suggested. It's not even plausible; the longer you spend in an elderly condition, the more likely you are to die. The only way to live longer is to restore a person's youth.
My condolences on your mother's condition. It is not reversible with current technology, but if she is given cryonic stabilization I see no reason to doubt that she might one day be cured of her aging and other illnesses. The cellular damage of aging is not greater then the cellular damage of cryonic preservation. Immense progress needs to be made to reverse both kinds of damage, but that's no reason to think it won't happen ever.
Why not? He said "It seems to me most likely", implying the "absolutely unavoidable" is a statement of qualified belief in a hard physical limit, not a statement of absolute confidence.
I've been spending time by my 87 year old mother's bedside. No one wants to live forever.
Ok, I think you meant to type Tithonius? See http://www.paleothea.com/My... .
This is flawed in two ways, however. OKCupid, as a dating site, is heavily driven by appearances, and to a lesser extent, writing ability. The two factors that make men the most attractive to women, in my experience- confidence and income- are not a factor on OKCupid, as openly advertising your income is frowned upon in American society, and confidence can't really be determined from a written profile. Yet both of these factors are generally higher in men over 30. Many men I know didn't find that women were very attracted to them until they were around 35+, established in their careers and making significant amounts of money.
likewise, in some cultures, older men are considered more attractive than younger ones, not only for financial reasons, but due to cultural perceptions and beliefs. This is especially true in Asia, where younger women frequently date and marry significantly older men who are not necessarily "rich".
Thitonius