Antiaging Has to Cure Frailty or It Does Not Work

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If we look at the mortality tables, it can explain why reversing aging damage reversal has to work very well for people to live very long lives.

Let us imagine that we are able to reverse aging damage so that someone is 65 or older has the same amount of aging as someone who is 65. This means for an average American man, then half of those people will still be dead by the time they have reached 95 years of age. This is because 1.6% of them are dying every year in the 65-year-old condition. Also, only 80% of them have survived from birth to the age of 65.

Asian American women in New Jersey live to a life expectancy of 93. Half of them reach the age of 93. Antiaging that reverses the aging damage every year for men so that they never get worse physically than when they are 65, get them to a life expectancy that is just beyond what Asian American women in New Jersey already achieve.

How about freezing aging risk and condition for an average American woman starting and maintaining at 65. Half of those women will still be dead by the time they have reached 110 years of age. This is because 1% of them are dying every year in the 65-year-old condition. Also, only 87% of them have survived from birth to the age of 65.

If the aging damage only reverses to the level of someone who is 70 or 75, then this is not hugely significant because the death rates are already very high. The population life expectancy statistics would not be much different than what exists for healthier countries or stastically identifiable groups within countries.

How about reversing aging damage and keeping someone as fit as a 60-year-old? This would mean American men could have a life expectancy of 110 and American women could have a life expectancy of 150. The average for men and women would be 130. The physical structure of people who are older than 60 would still have been reduced. Fully benefiting from removing cellular and systemic aging damage would mean rejuvenated older people would need to rebuild lost muscle and strengthen bones.

How about reversing aging damage and keeping someone as fit as a 50-year-old? This would mean American men could have a life expectancy of 170 and American women could have a life expectancy of 260. The average life expectancy for men and women would be 215. The physical structure of people who are older than 50 would still have been reduced prior to rejuvenation. Fully benefiting from removing cellular and systemic aging damage would mean rejuvenated older people would need to rebuild lost muscle and strengthen bones.

If we get really good aging damage repair for antiaging then people will have to be strong, healthy and alert or they will not be living extremely long lives. People cannot live another 50 years if they are in physical state of people who are currently 100 years old. They have to be revived or they will on average only last 3 more years.

SOURCES – Social Security Mortality Table
Written By Brian Wang, Nextbigfuture.com

36 thoughts on “Antiaging Has to Cure Frailty or It Does Not Work”

  1. For the other 3 suggestions obviously you don't want to go straight from mice to humans, you want to test on, say, pygmy marmosets first.
    The gene switch they put in the mice that allowed them to remove senescent cells would have very low risk, as you have to add a chemical to flip the switch. When the chemical is taken away, that elimination mode is turned off. Those mice had much better lives: https://www.nih.gov/news-events/nih-research-matters/senescent-cells-tied-health-longevity-mice
    Initially, you would do this exactly like the mice, but once the advantage is demonstrated, the chemical that triggers the switch can be changed to something the body produces when there is some level of senescent cells.

    Extending telomers is more speculative. And replacing/modifying mitochondria would obviously require extensive research, probably taking well over 2 decades. But it has the best chance of massive life extension as the main goal would be to reduce the body temperature 4 or more degrees, which would reduce all the dangerous metabolic reactions. This is probably why Bowhead Whales, naked mole rats, and various cold blooded creatures live so long.

  2. I made 4 suggestions, I admit this is just 1 of the 4. But we could substitute say 30 alleles that are common in humans with bad reputations to still somewhat common forms with good reputations for aging. With all the millions of people now being sequenced, they just can't be wrong so often as to get a worse result from those changes.
    We know there is a genetic component to Alzheimer's Disease, Breast Cancer, some other Cancers, Heart Disease, Stroke, Arthritis, Kidney Disease, Liver Disease, Glaucoma, Obesity, muscle wasting, all sorts of stuff.
    Take a look at the sample Promethease reports: https://files.snpedia.com/reports/promethease_data/Genos_example1_ui2.html
    In "topics" they list 33 genes for aging. Hundreds for "medical conditions".
    This one gives you 5.2x the risk of Arthritis:
    https://www.snpedia.com/index.php/rs6457617
    And there are lots of these stinker versions of genes, and they are common:
    https://www.snpedia.com/index.php/rs1010
    https://www.snpedia.com/index.php/rs10757278
    https://www.snpedia.com/index.php/rs2383206
    https://www.snpedia.com/index.php/rs1333049
    https://www.snpedia.com/index.php/rs501120
    https://www.snpedia.com/index.php/rs8055236
    https://www.snpedia.com/index.php/rs383830
    https://www.snpedia.com/index.php/rs7250581
    https://www.snpedia.com/index.php/rs5174
    Reducing the risk of the top 15 killers may not double lifespan, but it might double life expectancy, and should dramatically improve quality of life.

  3. Sorry, not enough sleep.

    Balance is one of the things that diminishes over time. If you are otherwise healthy and active but balance is not very good, then accident rates will climb. One of the measures of age is the time you can balance on one leg with your eyes closed.

    Maybe AI can harpoon you if you are falling off a cliff.

    There is also the problem of war getting easy and cheap using small flying AI drones, or using viruses that are configured to kill people of a specific ancestry…maybe using everyone else as incubator-spreaders.

    The most troubling thing is that governments are less and less inclined to get along today, when things should be improving. And in the US, division is being pushed by the media and ideologue politicians. These things can escalate, and many people could die. It is far too easy to convince people that they are getting a raw deal and others are benefiting or are indiferent. That allows a lot of hate to fester.

    On the positive side there is less lead, and that means less murders, and probably less suicide, because more people would feel in control of their lives.

  4. I said nothing about fewer accidents with more experience, and my 1333 year 'half life' was based strictly on the accident rate, ignoring murders and suicides and such.

    I did mention the possibility of a lower accident rate, but that was for increased safety measures over time, such as self-driving at super-human safety levels, and I didn't bother trying to roll that into my 'half life', which I fully expect is over-optimistic, which is why I mentioned "before other effects".

    Roll in murder, suicide, medical errors, etc on top of accidents, and the half life falls to around 450 years, which may still be optimistic, but technology will keep advancing and over a long life will keep boosting that number.

  5. I also assumed very early stage genetic modification.

    While you can probably verify that the genetic change you wanted to make is what you got, until you let the embryo develop you don't know with any certainty what the ultimate result will be – and I expect a lot (if not the majority) of times it will not be what was hoped.

    So again, to move faster with embryo experimentation will require methods that are nearly universally agreed to be unethical. I have no qualms considering that agreed approach "civilized", and the antithesis "uncivilized", much as I would like longevity research to move far faster.

    Maybe someday we'll be able to perfectly predict outcomes of genetic alterations, but that's likely decades away, and your basic claim was that working with embryos would move life extension progress along faster.

    MAYBE telomere extension is an exception – but even that doesn't seem guaranteed safe from unexpected consequences, which again puts us back into the area of questionable research methods.

  6. The bias I was referring to is referring to other cultures as "uncivilized"…and the actions of pursuing embryonic human modification as "unethical". The fact is people will disagree on what is ethical or not.
    I think those who refuse to modify their kids insuring them a miserable life, are the ones that are unethical.
    We are also talking in generalities. This is what I am thinking about when I think "embryonic modification" which may be quite a bit different than what you are talking about.
    I said "early embryonic stage" what I meant to say is "blastocyst" I see no reason to take any experiment past what is required. Division to 128 cells seems quite adequate to determine the success or failure of the modification. 
    I am talking initial modification at a very early division at latest the 8 cell level where any cell can easily become an entire person (totipotent cells). The other 7 cells, or less you remove and separate.
    I think any modification that they are serious about potentially taking to term should be paused and the blastocyst frozen while a couple cells are checked to see if the modification was made correctly. Only after that is determined would you thaw and implant. You can have a full genetic sequence done of a cell before modification (those unaltered 7) and a full sequence done on a cell after. You compare the two and look for any changes to the coding DNA or to any other DNA that appears to be "conserved". It is currently $299 for full genome sequencing.

  7. The fewer accidents with more experance does not fly. Accidents claim people of all ages fairly uniformly especially between 25 and 74. Less younger than that, and much more older than that. No soaring competence effect that we should see between 25 and 74: https://www.cdc.gov/nchs/data/dvs/LCWK1_2015.pdf
    age rate/100,000 (data was not available for population in the last 4 age groups so I estimated based on 2010 and the number of increase in the previous age group. Maybe I could have been more accurate, but the trend is clear).
    0-4 24.9
    5-9 3.7
    10-14 3.7
    15-19 18.6
    20-24 37.8
    25-29 44.2
    30-34 45.5
    35-39 45.1
    40-44 42.7
    45-49 47.1
    50-54 52.2
    55-59 50.2
    60-64 44.8
    65-69 43.2
    70-74 52.4
    75-79 84.9
    80-84 148.6
    85-89 234 10,523 deaths, pop. est. about 4.5m
    90-94 493 8,381 deaths, pop. est. about 1.7m
    95-99 738 3,396 deaths, pop. est. about 460k
    100+ 1,080 616 deaths, pop. est. about 57k

  8. Hey, you're the one that brought in the idea of some nations "allowing it" while others do not. The most plausible reason for disallowing such experimentation is ethical issues – not just experimenting on human cells (which most nations allow), but experimenting on live human embryos.

    Granted, once scientists think it is safe to attempt improvement of embryos intended to be brought to term, there probably will also be nations whose politicians ban such procedures. But that's far down the line yet.

    While some desired anti-aging target effects may be clear, it's less clear how those can be safely achieved, let alone what genetic changes are needed to safely implant those changes in the human genome, let alone how to reliably and safely make those genetic changes (genetic editing technology is improving but not close to 100% reliable yet).

    In general, I believe it'll long be considered far safer not to hack anti-aging into embryos that still have to go through a lot of genetic expression to grow into human babies, but rather to make changes to aging adults where treatment effects can be studied continuously and the treatment ceased if complications arise.

  10. Your characterization is a heavily biased one. They can make embryonic-like stem cells from ordinary tissue, make modifications and allow enough cells to divide to see how well it worked. When they can reliably modify just what they intend or verify that the other changes are not of concern, it is perfectly reasonable to apply it in the real World.
    People act like it is impossible to know what might be beneficial or delirious but many of the targets are fairly clear in regards to aging.

  11. "I suspect the gap of life expectancy between men and women will drop rapidly in the next 20 or 30 years." You gave no reason for this speculation. Women are more and more represented as age increases. If life expectancy increases, that gap should expand rather than contract. More than double the money is thrown at beast cancer than any other cancer: https://d2o7bfz2il9cb7.cloudfront.net/main-qimg-c2d747b8f87de19ab374ebb4b80f9438

    If there are breakthroughs with heart disease…maybe.

    But I actually expect an increasingly large gap as one of the main killers of the 110+ group is senile systemic amyloidosis (also known as Wild-type transthyretin amyloid). This is one of the main reasons men don't live as long as women. About a quarter of men over 80 have this and once diagnosed have about 5 months to live. You never hear about it, because they just throw it in with heart disease. This affects men far more often than women. Men make up 86.9% of the cases: https://link.springer.com/article/10.1007/s40119-020-00205-3

    The diseases that kill people at different ages are different or have radically different frequencies. When lots of people make it to 110 and beyond there will be a new set of diseases. Then probably another set at 120 and so on.
    From 45-79 the top killer is cancer, from 80 on the top killer is heart disease. But in the 100+ group, cancer only kills 4.1%.

  12. Certain countries may engage in unethical experiments on human embryos. Lacking the support and efforts of the civilized scientific world will greatly slow any such work, no matter how morally reckless the experimenters are.

    We will probably see nothing beyond fixing genetic defects in embryos for decades and I suspect even that won't be widely applied until in-womb genetic testing and manipulation becomes safe. For in vitro fertilization and testing, simply not implanting the embryo will very often be a much simpler option.

    Embryonic genetic improvements will probably not even be considered ethical until we've been able to implement the same changes in consenting volunteers and seen benefits sufficient to justify doing it to an embryo.

  13. Nonsense. Some countries will allow it, and reap the benefits. The others will be forced to follow them or be impoverished. At least by comparison.

    I am not saying it is ready for prime time this instant. There is science that needs done first. But genetic surgery will become a thing.

    We are learning what the genes do, not just by statistics, but understanding the variations in proteins that are made by a different gene alleles, and the effect on the function of these proteins. This is one reason protein folding programs are so important.

    All medical interventions are "experimentation"…until they are not.

  14. This was the fear…before they did tests and found out differently. Shortened telomers leads to fraying of the DNA this creates very destructive senescent cells that spew out all sorts of chemicals, and even ingest other cells. These senescent cells can easily give rise to cancer. 
    Jury is still out? Some studies say less cancer, others say more. 
    https://www.nature.com/articles/s41467-019-12664-x

    Another group of scientists followed families with very long telomeres. However, they already knew these families had a lot of cancer. That is what was being investigated initially. I think this tells you very little. There could just as easily be other families with long telomers and no cancer.

    The genetics are optimized for the likely child bearing years, everything else is compromised for that. So the length that is common for a 30-year old, would probably be great in a 90-year old, but it will have shortened by division and the 90-year old will have telomers far too short.

    The reality is that kids have the longest telomers, their cells divide the most rapidly, and they rarely get cancer.

    If we lengthen telomeres before birth, worst case, we may have 10x the cancer death in children. But that is 10x a very small fraction. Currently 2k/80m.

    Also ignored in all these decussions is that it is chemical exposure, sunburn, and viruses causing most of the cancer out there. Remove the exposure to the known carcinogens, eradicate oncoviruses, and modify to protect against cancer.

  15. Accidents take out about 52/100K in the US each year. Assuming equal probabilities across all ages (unlikely) and that the rate wouldn't decrease (e.g. far fewer auto accident deaths with good self-driving) each person would have a half-life of about 1333 years. Before other effects, of course.

  16. Anything having to do with modifying, let alone improving embryos is practically a non-starter, even if we had some way to know what interventions will ultimately be beneficial and non-harmful without actually doing human experimentation.

  17. Telomere length is on the wrong end of causation. Telomere shortening has a very important role, namely as a failsafe for cell lines that don't want to end (i.e. cancers). Obviously this failsafe can itself fail sometimes, but most of the time it works. For example, every mole on your skin is a potential tumor that was halted by shortening telomeres.

    You do see a larger number of shortened telomeres in aged animals, but this is a symptom, not a cause. The cause is a lack of new cell lines being created by your body, via stem cells. So any attempt to artificially lengthen telomeres would be counter-productive.

  19. As someone who trains mma I am well aware of the effects of aging. Now that I am in my mid 40s any tech that can reverse aging can't come too soon

  20. I just don't find that very believable. Regrets may accumulate, but our skills will become more honed and day to day we will perform well at the things we do. That generates a certain amount of satisfaction. Career changes, moving to another location, new hobbies…life has a lot to offer.
    Only teens kill themselves out of boredom. Some elderly get less joy out of life, but most of that is because of illness, weakness, frailty, lack of energy, the death and debilitation of friends or family and sometimes dissatisfaction with appearance. If you still look young and feel young, I don't see any of these things happening.
    Perhaps you might be looked down on as retarded, by comparison to all the modified people in the future that remember everything with perfect clarity, calculate like computers, and can create what we would consider artistic masterpieces at a whim. But probably only those who were very good at these things and attached their identity to these abilities would be prone to suicide when everyone else excels them.

  21. Many of the people into anti-aging are focused on making themselves live longer or people they know. If we focused on people not yet born, we could achieve much more, I think.
    We could extend telomeres in the early embryonic stage. We could also make the same change in humans that was done in mice that allowed them to eliminate senescent cells. There are many known genes that have better forms for healthy aging. We might even be able to replace human mitochondria with something better. There are so many species out there, at least one must have a better form.
    Maybe that is cheating, but these modification should simplify things. Though, we would still need to figure out how to stop some crud accumulations like glucosepane.

  22. On a side note, I've been reading Neil Asher's latest sci-fi collection set in his Polity universe. The current story I'm on actually details something that has only been mentioned in passing in all the many novels and stories that have come before. The protagonist is 172 and in excellent health with a youngish body (which will remain so indefinitely), but he's reached a crucial survival filter.

    The author posits that, usually as a person is approaching the age of 200, they start experiencing extreme ennui. Almost everything seems a repetitive pattern to them and they have a hard time caring about anything. Whereupon they either do the obvious, or start engaging in increasingly more hazardous activities (thrill-seeking) until their number comes up. Some of them pull through it and eventually find a new outlook that takes them on for many centuries thereafter, but this seems not to be a majority of them.

    I've also wondered myself if the "operating system" (our mind) that has come to us through evolution, could eventually require a complete reinstall — in which case, why bother putting a new mind in the leftover shell?

  23. I think if you want to know what conditions are really "aging" and not just more probable because of accumulation of exposure to toxins, infections, and sun damage over time, you have to look at progeria kids.
    Everything else could be prevented, I suspect, with healthy conditions.
    That is not to say that we know for sure that all the conditions that progeria kids experience are entirely genetic. They are still exposed to bacteria that cause tooth and gum disease, and many other bacteria that we are all exposed to that may cause conditions that aging makes us vulnerable to, but does not directly cause.
    Ordinary bacteria in the mouth has been implicated in heart disease/arteriosclerosis and other conditions.

  24. Life Expectancy is not a function of aging. Lives end from many other things other than aging. There are the obvious: suicide, homicide, accidents, disasters, negligence (manslaughter…very common…"more than 250,000 deaths per year are due to medical error in the U.S." https://www.hopkinsmedicine.org/news/media/releases/study_suggests_medical_errors_now_third_leading_cause_of_death_in_the_us ), war, booby traps like left over landmines, and animals (mostly bee stings and other stings and bites from insects, scorpions, snakes and spiders). But the heavy killers are toxins and infections: smoking, alcohol, acrylamide https://www.fda.gov/food/chemicals/acrylamide-questions-and-answers , radon, lead (causes high blood pressure which destroys kidneys), AGEs https://www.healthline.com/nutrition/advanced-glycation-end-products
    air pollution, crud that falls out of the air and settles on crops, and drugs prescribed to address some condition and cause damage. That drug may be the best we have to address the condition, but that does not make it harmless. And there is an enormous number of carcinogens: https://www.cancer.org/cancer/cancer-causes/general-info/known-and-probable-human-carcinogens.html Infection can shorten life in innumerable ways. And we can accumulate infections, because some infections are never completely eliminated: https://en.wikipedia.org/wiki/Virus_latency
    https://en.wikipedia.org/wiki/Slow_virus
    Then there is malnutrition, if the gut is not working well.

  25. Brian, I don't really understand the logic behind the title and argument that "Antiaging Has to Cure Frailty or It Does Not Work"? Is it even possible to remove the underlying damage that causes the diseases and conditions of aging such as heart disease and frailty without decreasing frailty at the same time.

    It seems like you're onboard with the idea that aging is caused by damage but then think frailty is a separate class of damage.

    The evidence emerging from senescent cell removal is that this one class of damage seems to contribute to almost all aging diseases and that there is cross talk with the other 6 classes of damage whereby an increase in senescent cells increases the rate at which other types of damage accumulate.

  26. You write about averages.
    Violence and incidents happens to people on a spectrum of outcomes.
    If you live in an Inner City, a Ghetto, your chances of being killed or die in an incident are pretty different than the chances of a man living somewhere else.

    And the other hand, if we are able to increase the healthy lifespan long enough we get to profit from other technological advancements that could increase the life span further and furthers.

    If I can live up to 90 (another 38), It will be 2059. Well past many technological Singularities

  27. You are getting me wrong. I am all for financing anti aging research. I'm just not that fond of financing life extending measures that leaves you impaired and confused. I think that the focus should be to solve the basic problem – aging – and not to stave off the last "system failure" just to have another one fail the next minute..

  28. The article is interesting, but seems to presume age reversal is followed by a kind of stasis. I have heard researchers (Dr. Sinclair, De Grey, Church) state that it will be much easier to reverse than to halt aging. So it is far more likely that, at least initially, age reversal will be performed periodically and there is no clear evidence of what the limit of rejuvenation will be, if there is any, so speculating that it will be 60, 50 or 40 is no more evidence based than stating it will be 20. Additionally, initial treatments will be uneven in the age related damage they treat and the efficacy with which they do so. Early treatment regimens are unlikely to show the kinds of longevity advances we would like, but deal in smaller extensions of life and larger extensions of health. In time, probably not very long from now, but who really knows, rejuvenation will be very effective and roll back the years significantly, followed X number of years later by a follow-up treatment. In an unknowable future span of years (probably closer than we think likely) the treatment will be performed once…or perhaps never if subsequent generations have the technology encoded in their genes. But I think Frailty will not be the stumbling block the article suggests.

  29. Perpetual frailty isn't even possible. It's a nightmare dreamed up by certain people to discredit researchers, but in reality it could never be like that. If you're frail, you're rapidly aging. If you're rapidly aging, you're not going to live long.

  30. That's exactly what it'll be. If you think about it, it has to be that way. Here's why:

    Aging accelerates the older you get. The tissue deterioration between, say, age 70 and 80 is far more than the deterioration between 60 and 70. So any treatment that can halt aging at a particular age would be able to reverse aging at a younger age. For example, a pill that halts aging at 75 would have to reverse aging in anyone younger than 75.

    This means that anti-aging treatments will create an unstable equilibrium. Either the treatment doesn't work for you, or it makes you get younger. There's no mathematical room for a middle ground.

  31. What if the treatment gradually repairs the damage from aging somewhat faster than it occurs, so that you 'unage' eg: a year for every year that passes. Start it at age 65 & by 75 you have the health of a 55 year old, by 85 are physically like 45 etc.
    Your chance of death would gradually decrease.
    Not as good as suddenly going from physically 65 to 25, but I would gladly take it if that is the best available.

  33. I suspect the gap of life expectancy between men and women will drop rapidly in the next 20 or 30 years. A lot of people say when ask say automatically i wouldn't want to live to a hundred until you ask then what if you have the health of a 40 years old they change there mind. A lot of people don't seem to understand that medicine is always advancing and regenerative medicine will become the standard vs what we have not just managing the symptoms of aging. They fail to see aging as a disease and all the symptom's that come along is just something inevitable.

  34. Good points. It’s also true that other things being equal, halting aging at maturity say 25 and curing all diseases would still produce an average lifespan only in the hundreds of years because of accidents and violence but would have a distribution frequency curve with a long tail into the thousands of years.

  35. I'd note that most 100 year olds do not commit suicide in despair over their condition. If you were already 100 years old, you'd likely be willing to endure it.

    Mind, if you were already 100 years old, that would already indicate that you were somebody with extreme outlier robust health, so maybe that's why they don't despair.

    But this point has been gone over endlessly, for literally decades: Aged, frail people who just mysteriously don't die, not only isn't the goal of anti-aging research, it doesn't even make sense. It pretends the death is somehow independent of the frailty!

  36. Brian is right and as a sidenote; who would want to live decades as a 100 year old? The healthspan is more important than the lifespan.

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