Most people misunderstand what aging is. It’s not just the public who have been deceived — Most scientists and medical researchers who study aging are on the wrong track.
The culprit is the “natural medicine” movement that has dominated thinking about our bodies for the last 50 years. “Respect the body’s wisdom. Work with the body to fix what has gone wrong.” This approach has worked so well with injuries and many diseases that it is understandable that people want to extend it to aging as well.
Diseases of aging have been treated as if they were something that goes wrong, something we have to help the body to fix. But in fact, the evidence accumulating in recent decades is that aging is not something that goes wrong, and the body is not trying to fix it. Aging is natural. It is the body shutting itself down, putting itself out of the way after it has done its job, finished reproduction.
How do we know that aging is an active process of self-destruction, and not just the body “wearing out”? There are a number of indications, becoming clearer all the time.
- For one thing, if the body were trying its best to keep in good shape, but can’t help wearing out over time, we would expect that damage to the body makes aging happen faster. On the contrary, most kinds of external damage actually make us live longer. The best example is exercise, which generates free radicals like crazy, tears muscles and puts little cracks in our bones. And yet, people who exercise tend to be healther and live longer than others who don’t. Starvation is also a way to live longer. Animals in the lab that are kept on very low calorie diets live much longer than those that have enough to eat. This is a clear indication that the bodies that get plenty to eat aren’t really trying to live a long time.
- If the body were doing its best to forestall aging, but succumbing eventually to wear-and-tear, we would expect that as we get older the repair functions would be going full-tilt. But in fact, all our repair and protection systems gradually shut down as we age. Stem cells, which produce new body tissues, gradually stop working. And the anti-oxidants that protect us from chemical damage are dialed down in old age, so we don’t have enough of such enzymes as CoQ10, SOD and glutathione.
- Clearest of all: there are actually self-destruction mechanisms that we can see in action. One of them is inflammation. When we are young, inflammation protects us from invading microbes, and kills diseased cells; but when we get old, inflammation is dialed up much too high; it kills healthy cells, inflames our arties, leading to heart disease, and inflammation causes cancer as well. Another mechanism we can see in action is called apoptosis, or cell suicide. When we are young, only cells that are diseased or defective remove themselves via apoptosis; but when we are old, healthy muscle and nerve cells simply fall on their swords and die, leading to weakness of muscle, weakness of mind and Parkinson’s disease.
This explains why “natural medicine” has been so helpful for infectious diseases, immune function and response to trauma, but in stark contrast natural medicine has failed to make headway against cancer and Alzheimer’s disease, and has made only marginal progress against heart disease and stroke.
For these diseases of old age, we need to abandon the natural approach, and instead simply trick the body into thinking that it is younger. Then it won’t try to shut itself down.
In fact there are some intriguing indications that this might work. There are researchers working with this approach and they have produced some dramatic successes just in the last few years:
- Every chromosome in every cell contains a time-keeper, tacked onto the tail end of the DNA. This is the “telomere”. Simply by resetting the telomere clock, scientists have produced dramatic results in lab animals, reversing aging and making animals younger.
- When the telomere clock signals a critical age, the cell becomes “senescent”. It goes and strike and refuses to do its job. Worse yet, it sends signals to nearby cells that cause the other cells to become inflamed and cancerous. Recently, scientists have had remarkable success making mice live longer simply by removing the small number of senescent cells.
- As we get older, the hormones circulating in our blood gradually change. This is the principal way that the body knows how old it is. There are youth hormones that promote rebuilding and high-efficiency energy output; and there are old-age hormones that turn up inflammation and cell suicide and signal the body to gradually destroy itself. Scientists have begun to have success by increasing the former and decreasing the latter, resetting the hormone profile of an old animal to match that of a young animal.
These approaches have not yet made front page news, but scientists in the field already recognize their dramatic promise. If all goes well, we should expect breakthrough treatments that extend life and prevent the debilitating diseases of old age, coming on-line in the next few years.
Disclaimer: This is my own perspective, shared by a handful of world-class aging scientists, but it is not yet mainstream. In addition to the two views described here–programmed aging and wear-and-tear theories–there is another class of theories favored by mainstream evolutionary scientists, based on compromises that evolution has been forced to make. These compromises have been made up ad hoc to avoid the inference that aging evolved to benefit the community, not the individual.
There are a great deal of genetic phenomena, as well as hormesis, that can only be explained by programmed theories
Seems very unlike Aubrey de Grey’s description of aging as the side effects of accumulated damage–exactly the wear-and-tear.
Love your input but I still think his argument is more convincing.
I believe that aging is more complex than could be explained by one single “school of thought”
(programmed vs wear-and-tear damage).
But I do have a simple question regarding wear-and-tear: if that is the only cause, we could
simply experiment with organisms
and isolate them, reducing drastically wear-and-tear damage. Wouldn’t that lead to exceptional
I think science in reverse aging will progress faster, if the two line of thoughts will
integrate instead of fighitng each other – at least for a while until things get understood
in more depth. This is similar to a certain degree with wave-particle duality in physics.
Try to explain all using one side and you fail. So I think, up to a point programmed take
more prevalence, then wear-and-tear is more visible (or vice-versa, or combined).
We are all on the same boat with aging, regardless who/what causes it – the faster we solve it, the better.
Grudgingly, I have to agree with you. Aging is natures cruel joke. It’s a way of telling us that we are growing useless and it’s time to make way for others. Never mind the fact that many of us oldsters still contribute to society. In natures mind, it’s all about sex. The plumbing doesn’t work anymore, so who needs you. However, there is a contradiction here. If the sole purpose of nature is to preserve and procreate the human species (or any species) than why not continue the lives (and reproductive years), of those members of society who have contributed the most to the gene pool. Why do great people die young while some scum-sucking SOB lives until he’s 90. It all seems very arbitrary.
Nature has to apply the same rules to all living beings. It won’t make an exception just because humans feel they are more important. It is up to us to make that exception a reality.
Exactly, evolution is an arbitrary process.
First off, you are assuming evolution has a plan, or directionality, which it does not. Natural selection does select the most “fit” individuals in an environment, but environments vary greatly (as ours is primarily intraspecial now). And to be honest, your claim seems like an anecdote, and I do not believe it to be objectively true. Within our species, sexual selecton is an important part of evolution, and the most common attractive attribute (for both sexes) is kindness (http://blogs.scientificamerican.com/beautiful-minds/is-kindness-physically-attractive/)
To counter your other assumption, “if the sole purpose of nature is to procreate and preserve the human species…” Like I said before, evolution has no “purpose,” but it does have processes. Genetic variation is the most important process that leads to evolution. Because of this, it is evolutionary beneficial to die, since immortality (or negligible senescence) eventually obstructs variation within a population.
Aging isn’t just one thing. It’s not just the telomeres, or the hormonal changes. There’s also the accumulated DNA damage which leads to cancer. And there are the evolutionary compromises, which you mentioned briefly at the end. One notable example of this is how children learn some things faster than adults. The brain shuts down expression of certain genes after childhood, and it’s know that drugs like valproate can reverse this effect. Why did evolution make this tradeoff? Because all that extra brain activity requires more sleep, and that would leave us with fewer working hours. That was a useful tradeoff a century ago, but maybe not for some people today.
Yes – Aubrey’s argument makes a lot of sense, and he appeals to what we instinctively feel must be true. But the genetic evidence is piled up against this view. I’ve just completed a book listing that evidence which should be out in a few months. In the meantime, you can read a version of the same thinking here.
You say, talking about Dr de Grey (quote) …and he appeals to what we instinctively feel must be true… (unquote)
If science is true then yes he does. I have rarely seen someone that listen to criticism so much as Dr de Grey and actually answers it too. You are trying to make him look like he is fooling us into ‘believing’ in what he thinks but he is not. He is delivering Science and if you want to disprove him, you must disprove his science.
That the body is “programmed” to die (an old idea) is just wishful thinking as you then could be able to ‘stop the death gene’ or something. Also you have no hard proofs about it (the programmed aging), all your examples can be tracked to the wear and tear in one of the most long lived animals on planet earth.
Aubrey is a friend, and I would never imply that he has misled anyone intentionally. I think there is no one in the world who has done more to change cultural attitudes toward anti-aging science. He and I have discussed this issue at length, especially in the last year. There is a great deal that we agree on, of course. But we disagree about the evolutionary significance of aging, and that has consequences for the way we go about looking for anti-aging fixes. There will be a special issue of Current Aging Science this Spring devoted to this question, with contributions by Aubrey and by me, and several others.
I agree that Aubrey is a delight to talk to, and a sponge for information. I have learned a great deal from him, and from the biannual meetings he has organized. He and I disagree on this one question, and I think the science is developing so fast that in the next year or two the issue will be resolved.
Regards the science of sens. We now have the bowhead whale genome, a multicentury lifespan mammal, that some consider exhibits negligible senescence. Yet it is clear from the start that sens antiaging solutions such as WILT were not necessary to implement by nature to attain agelessness. The suggested sens solution of transferring all remaining mitogenes to the nucleus also seems to not have occurred, but it can be checked now that the genome is sequenced.
So in some sense sens might be overengineering, as nature manages to exponentially increase lifespan between species with small genetic changes.
Considering that taking growth hormone or testosterone makes us look younger and ages us quiker makes me wonder about ur third bullet point. We need things to make our mito work better whatever that will be. (Diet is the best we have at this point) low polys with a youthful ability to process glucose which would require higher carbs and lower fat than a lot of typical low carb diets.
I was thinking not of HGH but of oxytocin and GDF11, rejuvenating propoerties of which have just recently been discovered.
I don’t recommend HGH, but there have been commenters on this blog who swear by it.
Yes, HGH. Just what old people need, more medication.
I don’t see how we’d fix aging without giving medication to old people.
…or giving hormones to middle-aged people so that they don’t grow old.
If there was a way to “repair” one’s own DNA and reintroduce it into the body, i would have no problem with that.
I believe that DNA damage during the lifetime plays a quite minor role in human aging. Some say it plays a major role in cancer, but my view is that cancer is something that happens to us all the time, but our immune system very efficiently catches it before it gets to be more than a few cells at a time. It is when the immune system declines in old age that cancer becomes a threat.
Could that last point about hormones changing as we age be partly responsible for the rejuvenation and anti-ageing effects of replacing some of an old person’s blood with that of a young person?
Swapping out young for old plasma for rejuvenation has been tried before, in the late 1960’s. Remember Dr. Orrenreich and his youthified beagles? There was even a clinic in NY, on Fifth Ave. I think, that specialized in the procedure. IIRC it wasn’t that effective and I think it just fizzled out by the early 1970’s. The process got a good bit of press at the time and was written up in the book “The Youth Doctors,” by Patrick McGrady (1967).
I didn’t know about this and it looks to be important information. How do you happen to know about it? I can’t find references in Google or Wikipedia. The McGrady book appears to be available from Amazon resellers for $0.01 + shipping.
Having a copy of the book, from when it was published, I took a look at what it said about Orentreich and his procedures. Apparently he was trying to follow the work of a French biologist Alexis Carrel who “found that only young serum was able to keep his famous chicken heart alive and beating in a dish for thirty-two years. When old serum was added to the chicken heart tissue cultures, the organs promptly expired”. It reports that there were “seventeenth-century experiments , in which at least two old mongrels were apparently rejuvenated by transfusions from young pups.” It is also reported that Rockefeller University has Carrel’s original papers to which Orentreich was given limited access. However what Orentreich did is quite different. He ‘thought’ that the blood accumulated ‘toxins’ and that cleaning the blood of these toxins would rejuvenate a person. This was accomplished by withdrawing blood, removing the plasma and reinserting the RBCs. He did this on dogs in a controlled test although the results are not reported. The author was present at the first human test, in which two pints were withdrawn and spun down, but the patient refused to have the RBCs reintroduced. The author comments that he has been told that other patients volunteered and are being regularly plasmapheresed. pp 307-310, copyright (1968). While Carrel might have been doing something similar to what is under current speculation, it seems that Orentreich may not have paid enough attention to Carrel. He was/is? an MD who was apparently a very successful plastic surgeon, inventing techniques for addressing hair loss.
Simple empirical math doesn’t support the wear and tear argument.
uh…could you be more specific?
As the author of the blog post that Lucas linked to, I actually think it aligns very well with what is written here. The short version: the statistics of human mortality suggest that aging does not comes from a gradual accumulation of damage to the body, but instead from a slow shutting down of the body’s defense and maintenance systems.
Prof. Mitteldorf, if you have any comments on that blog post (which comes from a very naive perspective), I would be glad for them.
How would an intentional self-destruct mechanism ever evolve? It doesn’t make sense. The most one can say is the conventional view that there is little evolutionary pressure to create self-repair mechanisms that persist longer than the generation time after which genes have already passed on to numerous descendants.
Yes – it doesn’t make sense. This is what I realized 18 years ago, and this is the paradox I have devoted myself to explaining in the years since.
The one-line Executive Summary is this: Every species depends on a stable ecosystem, and no stable ecosystem can be constructed from species that are evolved to grow exponentially at the fastest possible rate. Population overshoot and collapse is a rapid and deadly dynamic, and therefore avoiding it is a powerful evolutionary imperative. Almost all species have evolved to bring control of death under control of the individual’s genes. If individuals were not programmed to die individually, then they would all die at once, and that would be extinction. Read more at http://joshmitteldorf.scienceblog.com/2013/07/01/the-demographic-theory-of-aging/
How could DNA evolve to avoid a one time extinction event that never actually happens?
I’m very much a science lay-person, but your view of how evolution intelligently designed dying up front, using multiple processes and across most lifeforms, seems opposed to how natural selection works, which is a reactionary process.
Of course natural selection can’t anticipate events. Many extinctions happened in the deep past before aging and other adaptations for ecological stability were established in the genome.
That makes sense and is interesting. Can you point me to some more info on these pre-aging mass extinctions?
I wonder if there is something more basic to explain it – something inherent in the nature of life itself.
I don’t really know exactly what but when we think from a thermodynamic perspective life seems to temporarily outwit the Second Law. I think someone (can’t remember who) said that if life doesn’t violate the Second Law it violates the spirit of it. It might be that this temporary violation (of the spirit of it) may carry with it the cost of eventual death.
From the point of view of thermodynamics, life is a scheme for taking in free energy, using it to build order within, and dumping entropy back into the environment. This is what makes life, life. Yes, it can go on indefinitely – there is no thermodynamic necessity for aging. Read more…
Very interesting post. I agree with you that one of the most promising approaches is to identify the differences in hormones and other circulating factors in young and old animals and then try to keep these at ‘young’ levels.
Telomere rejuvenation has been shown to be successful in Mice by M.Blasco at the CNIO in lifespan increase as well as tissue restoration. They are hoping to move to testing in pigs next but progress is painfully slow. The restoration of Telomeres to a younger optimum length would likely help restore the system somewhat towards a more youthful balance too, it would likely boost the imune system and help avoid Cancer too. We need to get this therapy closer to human testing but so far I only know of two groups working on it and both are limited by funding.
Senescent cell removal is a good move and stem cell technology could replace lost cells. However progress in making something that targets these cells is slow, I believe SENS is working on something but how long that will take is anyones guess.
Resetting Hormone patterns to encourage a younger Phenotype has merit if all the factors could be identified and regulated properly. Simply using GDF11 is not going to cut it the whole lot would need identifying and regulating.
The combination of these three would likely give lifespan a huge boost but developing and getting them passed will be a major barrier due to how the system works.The FDA would also not approve the therapy anyway unless it treats a named condition and it would only be available to those with said condition.
The FDA would have been a significant barrier 20 years ago. Today there are many countries that have equivalent technology infrastructure & training with the willingness to progress these therapies. In some cases such as Japan it maybe imperative to move this along.
Funding is the problem and the lack of proof that therapies work in the Human body. We know Telomere rejuvenation works in mice for example but getting such a therapy into human trials will take decades.
GDF11 is also promising but it is only one of many factors in blood that help restore the body. How long will it take to identify and regulate such complex systems with the lack of funding?
Would it be possible I wonder to look at species with very long lifespans and see how they do it?
Certain species of large turtles come to mind; Aldabra Giant Tortoise, perhaps certain mussel species (they can live for hundreds of years until eaten), and so on. It may be a lot simpler than we think it is … with the right genes turned on or off.
Also off topic, but I think my comments disappeared from the other posts? Not sure if it’s a WordPress issue or something else.
It may be simpler than that. I think we can do gene expression profiles of young people and old people, and compare them. We may be able to restore gene expression in an older person to what it was when s/he was younger, and I expect that alone would be a powerful anti-aging therapy.
Parabiosis experiments show that hormone levels etc. can rejuvenate. Telomerase activation is important as well (but then I would think that, since I worked in the Shay-Wright lab).
Aging may have several components, but fixing even a couple of them could have huge effects. Bowhead whales live over 230 years, and they’re genetically nearly the same as cows… little tweaks are important 😉
Hi Josh, I just love your blog and reading about aging and life extension.
However, I just read about your poor 95-year-old mother having a stroke. That is when life extension gets personal. I don’t think there is any reason in this day and age for anyone to have a stoke, whether it was a bleeding stroke or an artery clogged by atherosclerosis. They are both caused by the same thing, a lack of vitamin C, which costs about 5 cents per day. I know everyone thinks I am a kook when I say that, but hear me out:
We know most of the lower animals make their own vitamin C in their livers; but humans and the great apes do not. (This is probably a case of evolution limiting our lifespans to make room for the next generation). One thing C does is act as a coenzyme in the secondary synthesis of collagen in which 3 collagen molecules are twisted together and then cross-bonded to form strands of collagen that are as strong as steel for their size and weight. What happens when there is not enough C? These collagen molecules do not get completely cross-bonded, and are used in their weakened condition. Collagen is used to hold everything together, including the arteries. Weakened collagen used in arteries leads to weak arteries which can blow out, causing a bleeding stroke, or can be reinforced inside with calcium and cholesterol deposits, which eventually lead to plugged up arteries.
All humans are born with heart disease; because they cannot produce enough vitamin C to produce strong collagen, and cannot get enough C out of their diets, even if they lived on orange juice. This shows up in children as spontaneous nose bleeds, black and blue marks on their arms and legs from playing sports and fighting at school, and bleeding gums when brushing their teeth. It eventually causes heart disease in older adults, but shows up as atherosclerosis in 50% of the young military men who were killed in Korea and in Vietnam.
An animal the size of a human produces about a thousand mgs or more of C in its liver every day. It is a good guess that humans need about the same, although a careful study shows a need for only 500 mgs. Nevertheless, since C is not completely absorbed, a 1000 mgs is a safer bet. Too much C (like about 3,000 mgs) will cause diarrhea. This will clear up in a day, if one skips their vitamin C for a day.
All of this has been known since the year 2000. You can read all about it for free by searching the Internet for “Why animals don’t get heart attacks…. but people do”. You can down-load the book for free, 10 chapters; but just reading the first chapter will convince you.
Now back to your mother. You have to get her on a thousand mgs of C each day. I suggest 500 mgs in the morning and 500 mgs before bed, or with meals. The good news is that this is enough to slowly cure her over a year’s time; because the body slowly replaces its collagen molecules with new ones; but any damage from her stroke will probably remain. This will also slowly remove all the calcium and cholesterol plugging up her arteries. However, she will still be at risk for a year; so you need to speed it up by also giving her a daily supplement of 500 mgs of lysine and 500 mgs of proline (available over the Internet at a reasonable price). Lysine, proline and glycine are amino acids used to make collagen. Because she is at risk, I also suggest an extra 2000 mgs of lysine, which will help dissolve the cholesterol, and keep it in solution in the bloodstream, instead of attaching to the wall of the arteries.
Please read the book by Dr. Rath!
P. S. You also need to be taking a thousand mgs of C every day! I would also suggest you take a dose of C60 everyday to prevent cancer; but that is just a suggestion for now, until we get more proof that C60 prevents cancer. C60 is available off the Internet from C60 Vaughter.com, for about $20 per month.
Jerry, how do explain that blood plasma level of vitamin C does not rasie above a certain point once you go above 200 mg intake of vitamin C per day? It doesn’t make sense to take megadoses, if the reaming 1800mg gets excreted and you get diarrhea as a bonus.