A new study has appeared to support an old idea: Aging is inevitable and immutable, so anti-aging research is doomed in advance to failure.
In 1957, George Williams wrote
This conclusion banishes the “fountain of youth” to the limbo of scientific impossibilities where other human aspirations, like the perpetual motion machine and Laplace’s “superman” have already been placed by other theoretical considerations. Such conclusions are always disappointing, but they have the desirable consequence of channeling research in directions that are likely to be fruitful.
In 2002, three prominent aging scientists wrote (in Scientific American):
No Truth to the Fountain of Youth:
…no purported anti-aging intervention has been proved to modify aging…We find it ironic that a phony anti-aging industry is proliferating today…Some [researchers] Some assert that aging’s complexity will forever militate against the development of anti-aging therapies.
One of the three was Len Hayflick, who is most famous for having discovered and documented one of the clearest and most preventable mechanisms of programmed aging.
In 2017, Joanna Masel wrote
“Aging is mathematically inevitable. Like, seriously inevitable. There’s logically, theoretically, mathematically no way out.”
This new study is based on statistical analysis of human and primate populations. Among the 42 authors (!) who signed it, I am chagrined to find the name of J. W. Vaupel. Et tu, James? Over several decades, Vaupel has been the optimist of demography, telling us that somewhere in the world, human lifespan is always continuing to increase, as it has done since 1840, at the rate of about 1 year of new lifespan for every 4 years that passes. For the first 130 years of this advance, the improvement in lifespan was predominantly about preventing infant mortality and combatting infectious disease. But since about 1970, lifespan improvements have continued to benefit the elderly. My informal index is the number of 80-year-olds I see on the tennis courts. Vaupel and his former student, Annette Baudisch, also were prime movers in a comprehensive 2013 study of Aging Across the Tree of Life, which catalogued species that don’t age at all for decades at a time, and others that become demographically younger.
This new computer model—like all computer models—is a translation into mathematical language of a set of assumptions about a natural phenomenon. The crank turns, and out pops a prediction. The sleight-of-hand, the conjuror’s trick, is that we are tempted to look at the mathematical machinery to see where these predictions come from. But equally important is to look at the assumptions on which the mathematics is built.
In this case, the assumption is that natural selection has been trying to maximize lifespan, because the longer an individual lives, the more opportunity it has to reproduce. And reproductive output is the measure of success in neo-Darwinian logic.
But if we look at the biology of aging, it’s clear that evolution has not been trying to maximize lifespan. As we get old, genes are turned on that destroy us with inflammation and autoimmunity, and this epigenetic change shows every sign of being under the body’s control. As we get old, genes are turned off that rebuild and protect the body against chemical damage, most famously from free radicals. Again, it appears that this is deliberate. It is a product of natural selection, not a constraint on natural selection.
How can this be? How can a variety with lower reproductive success prevail in evolutionary competition against other varieties with higher reproductive success? This question has been the primary focus of my own research for 25 years, and
my answer is the necessity to preserve stability of ecosystems.
My answer may be right or wrong—it is still a minority opinion. But what is clear is that the lifespan of almost all living things is under epigenetic control. That is, aging is a programmed phenomenon. Aging is not the accumulation of damage. Aging is not the body wearing out. Rather, aging derives from processes of self-destruction that are under the body’s control.
In this perspective, aging looks a good deal less inevitable than this article claims. And indeed, there is cutting-edge science that appears to be turning back the clock of aging,
turning old rats into young rats.
Specifically, what does the new study find? Looking at populations of humans and other primates, they find that longer average lifespans are associated with less variability in lifespan. In other words, the short-lived primates have deaths that are spread out, with some living much longer lives; but in the longer-lived primates, age-at-death is clustered up near the high end. This gives the appearance of some kind of wall at the high end of lifespan.
And where, specifically, is the flaw in the new paper?
“Understanding the nature and extent of biological constraints on the rate of ageing and other aspects of age-specific mortality patterns is critica…”
The implicit assumption about “biological constraints” is that the constraint is physical, or that in some way it is beyond the reach of evolution. The assumption is that natural selection has pushed against these constraints, and hit a brick wall. The alternative view (a view that is shared by some of the most prominent researchers who have studied physiology and biochemistry of aging) is that these “constraints” are actually baked in by natural selection itself. Far from being constraints on evolution, these constraints are actually the product of evolution. This is to say that the constraints are not fundamental physical limits, but features built into the epigenetic cycle of growth, development, and aging. The “constraints” become malleable as we tinker with the signaling mechanism by which the body imposes aging on itself.
A crucial caveat
I believe that as we understand more about epigenetics and the signaling mechanisms that control biological age, it will become increasingly feasible to manipulate lifespan. Indeed, we’re already doing this to a huge extent in lab worms and, to a good extent, in rodents.
But evolution isn’t so dumb. Limits on lifespan have been put in place to help protect against population overshoot. And (my opinion) humans are already in a state
of severe population overshoot, in the context of sustainable limits of Earth’s biosphere. I believe that whether or not biological science succeeds in further extending lifespan, it is an urgent matter for survival of our species (and many other species) that we shrink the human footprint on the biosphere and on the soil, water, and atmosphere that support Earth’s ecology. I think that living well with less is a relatively simple
technical problem. We need only implement all
currently known efficiency improvements in the use of resources, and continue to discover new ones. But it is a huge
political problem that we have barely begun to confront, and I don’t have any good ideas how to make these changes a political reality. I’m going to stick to the science, and count on others who are more adept at politics than myself. As we extend human lifespan, there is an urgent need to move toward sustainable agriculture and to adopt energy-efficient technologies.
Discussion
151 reader comments
Imported threads are marked Archive. New comments are welcome and moderated for spam.
" As we extend human lifespan, there is an urgent need to move toward sustainable agriculture and to adopt energy-efficient technologies."
And even more urgently to spread human civilizations off planet Earth.
I dont know if my reply to Rick Davis was posted so here goes:
Hi Rick,
As many of you wrote to me about doing a fully body application self conducted trial with cytokine readings before and after 30ml would be too less per bottle. So on Amazon both 30ml and 100ml will be available for the soft launch to our community we will keep only 100ml.
Yes we were really happy to see the results of the ongoing lifespan study. We have also done grip strength and are in the process of sending DNA samples to Horvath Lab/Clock Foundation. Interestingly for the first time next week we will be administering a 3rd dose. Really keen to see results on these subsequent doses to see if there is any cumulative effect or if at some dose aging stops.
Akshay,
I have a couple of questions. A couple of months ago you indicated in a post that the Blue Gel would come in a 30ml unit size, and that to participate in the systemic effect trial, you would need to apply Blue Gel two times per day. In a more recent post you indicated that the unit size would be 100ml, and that the Blue Gel would need to be applied 3 time per day. Have you changed the formulation? Has the price per unit changed?
I saw the update for your E5 longevity trial on the "Modern Healthspan" Youtube channel. The results for IL-6 and TNF-alpha were impressive. Congratulations! Are you testing other parameters than the above two that you have already shared?
Thanks,
Rick
Hi Rick,
As many of you wrote to me about doing a fully body application self conducted trial with cytokine readings before and after 30ml would be too less per bottle. So on Amazon both 30ml and 100ml will be available for the soft launch to our community we will keep only 100ml.
Yes we were really happy to see the results of the ongoing lifespan study. We have also done grip strength and are in the process of sending DNA samples to Horvath Lab/Clock Foundation. Interestingly for the first time next week we will be administering a 3rd dose. Really keen to see results on these subsequent doses to see if there is any cumulative effect or if at some dose aging stops.
A bit off topic but I really need a right information if you could help me. Do you know if Sulforaphane and DIM interfere with antibiotic doxycycline?
As always, consult your doctor for any medical advice.
However, having said that, I wouldn’t worry too much about a possible drug interaction with doxycycline, as sulforaphane has little or no effect on cytochrome P450 in the liver.
https://www.liebertpub.com/doi/10.1089/jmf.2016.0063
Nanaka:
It appears that broccoli & Kale may reduce the ability to absorb the Doxycycline. It will at worst make the doxy less effective.
Can you take the nutrients apart from the Doxy, by eight hours or at least a four hours to avoid decreasing absorption to much?
If not, it may be best to stop taking them temporarily, while using the Doxy, to maintain the drugs full effect
Dim and Sulphoraphane Both are found in Brassica vegetables
Iron supplements and iron-rich foods — such as liver, sardines, beef, lamb, eggs, canned salmon, legumes, tofu, wholegrain cereals, kale, broccoli, spinach and certain seeds and nuts — may also affect your body’s ability to absorb doxycycline.
Dim: (3,3′-Diindolylmethane) is a compound derived from the digestion of indole-3-carbinol, found in cruciferous vegetables such as broccoli, Brussels sprouts, cabbage and kale.
The elimination half life of doxycycline is between 16 to 22 hours (for healthy adults). This is the time it takes for your body to reduce the plasma levels by half.
Thank you Heather, awesome information!
Nanaka:
just noticed that Heather didn't mention dairy products, which should be avoided prior to taking doxycycline (most likely also mentioned in the package leaflet).
You probably already knew that, but just to be on the safe side.
Yes, I know it but thank you, I really appreciate it.
Hi Nanaka:
Sadly, a large percentage of traditional Allopathic doctors do not even know what DIM is.
Exactly! You do not know what’s up outside the US, even worse!
Ok just received a very sad update from his friend Walter who is in touch with Josh’s daughter Sarah:
Josh was hit and run on his bicycle. Hip, leg, arm, etc. broken. Already had several surgeries. Much internal bleeding, but he's awake and safe now. Will probably be in the ICU for two more weeks, according to his daughter, and will probably never be able to run or hike again, etc.
I hope that there were cameras in the area where his accident occurred. He will be in my thoughts.
I am praying for the best recovery.
I hope he recovers the best
Thank you for the update on Josh, Askay.
I am still praying for Josh.
Hi All followers of this blog. Just heard the very sad news of Josh's accident on Wednesday. For all who don't know he is in ICU. Let us pray for his speedy recovery.
So sad news, praying for his speedy recovery ❤️???? .
I hope he recuperates well.
Hi Askay:
Thank you for the Head's up.
I hope Josh has a very speedy recovery. Please keep us posted, if you can.
2 more replies
Best wishes to Josh for a speedy and full recovery.
Any more word on Josh’s condition?
We are trying to reach his daughter Sarah but have not been successful so far. I wanted to fly there to cheer him up but can't do so till we get latest update on his condition. I did a prayer for whatever its worth for his recovery. Accidents are so tragic because we could have avoided by not being at that spot at that time, especially if it isn't our fault.
Any news on how Josh is recovering?
As always, consult your doctor for any medical advice.
However, having said that, I wouldn't worry too much about a possible drug interaction with doxycycline, as sulforaphane has little or no effect on cytochrome P450 in the liver.
https://www.liebertpub.com/doi/10.1089/jmf.2016.0063
Thank you Ole. Unfortunately, doctors know nothing about it. People here know even more than they do.
Josh have you seen this?
https://www.geertvandenbossche.org/post/why-the-ongoing-mass-vaccination-experiment-drives-a-rapid-evolutionary-response-of-sars-cov-2
Molecular epidemiologists have observed that mutations within the Sars-CoV-2 spike (S) protein of these emerging, more infectious lineages are converging to the same genetic sites, a phenomenon that coincided with a major evolutionary shift in the landscape of naturally selected Sars-CoV-2 mutations (1).
Significant convergent evolution(*) of more infectious circulating Sars-CoV-2 variants is not a neutral, host-independent evolutionary phenomenon that merely results from increased viral replication and transmission but is strongly suggestive of natural selection and adaptation following a dramatic shift in the host(ile) environment the virus is exposed to (1).
Molecular epidemiologists fully acknowledge that the pandemic is currently evolving Sars-CoV-2 variants that “could be a considerably bigger problem for us than any variants that we currently know in that they might have any combinations of increased transmissibility, altered virulence and/or increased capacity to escape population immunity” (1). This is to say that phylogenetics-based natural selection analysis on circulating Sars-CoV-2 lineages strongly suggests that viral variants resistant to spike (S)-based Covid-19 vaccines are currently expanding in prevalence and highly suspicious of causing future epidemic surges globally.
Deployment of current Covid-19 vaccines in mass vaccination campaigns combined with the ongoing widespread circulation of Sars-CoV-2 can only increase immune selective pressure on Sars-CoV-2 spike protein and hence, further drive its adaptive evolution to circumvent vaccine-induced humoral immunity. In this regard, the expectation of an increasing number of vaccinologists matches the current observation made by genomic epidemiologists in that S protein-directed immune escape variants are highly likely to further spread and expedite the occurrence of viral resistance to the currently deployed and future (so-called ‘2nd generation’) Covid-19 vaccines.
With all the DNA/mRna studies being done it is being said by scientists that ageing is a hiccup in our genes and that ageing (now being recognized as a disease) may be more easily "fixed" than many cancers.
Also it is more recognized that "underpopulation " may be a more imminent threat than what we have been warned about for years. Look at the "fertility rates" of almost all nations, including so called third world countries.
Countries like Japan, South Korea and Thailand are under1.0 replacement rates. Europe has been taking in immigrants for years.
I've seen where the USA is at 1.7 and falling below the 2.1 to keep the population at the current number.
Hiccup is quite an understatement. It's programmed at a deep level, but I agree it is easier to slow aging than to cure cancer.
Overpopulation seems already to be a problem, and we either need to change our habits to use resources far more efficiently or agree to limit everyone's individual right to reproduction. Either of these requires changes in culture that I don't know how to approach.
Regarding the overpopulation problem, it looks like this is being caused by a fall in death rates rather than rise in birth rates. In under developed African countries going through the transition to low child mortality this is most pronounced as birth rates have not yet fallen to developed levels, but to a lesser extent it is being mirrored in developed countries at the other end of the age range with far more older people surviving for longer in a dependent state. My little town in central England only has 1000 people living there, but has 2 large old peoples' accommodation. Solving aging would make these people productive again, but would make the overpopulation problem even worse. But in England birth rate are low and drifting lower. Can we even contemplate rolling out such a treatment to countries with high birth rates?
This assumes that nations with high fertility will continue to have high fertility after getting access to anti-aging therapies. High fertility is ultimately economic. The opportunity costs of having children skyrocket as societies become more prosperous.
Very true, but as I pointed out there are rocketing populations in countries transitioning from high to low fertility, and I'd expect something similar in countries transitioning to an ageless society.
In general as soon as women are educated tend to give birth to less children if any at all. in some cases In South Korea the birth rate per woman is 0,95 kids. This is far less than one.
In Europe birth rates go down steadily. So they do everywhere except some countries in Africa (where women are uneducated, just give them time, if you check gapminder you'll see that even those high birth rates are not as high as they use to be, and decrease every year, as they are being mitigated by women's education, just like they have been in other countries).
In Africa kids are still working force and old age insurance for the parents, which is absolutely undesirable. Most of governments try to take action on that.
For good or for bad, many of my girl colleagues from the Polytechnical University are childless, or have just one kid. Personal decision, most of times.
It is something unthinkable for me, but many women seem to be comfortable with that.
Besides I have the feeling that many people think that we are solving death, and I think the pandemics show us clearly that we are not solving that.
The fact is that developed countries have aged amazingly and the pandemics have been the cause of death of at least 4 million people in the world. Seem few, and every death is a loss, and a drama, and I lost my mother just before pandemics and every time I read about the death of the elderly by COVID was a painful reminder of her loss.
But I think that we are being too optimist too fast, E5 might be the amazing discovery of the Century (and probably would broke many fertility clinics, as most of them treat women with age related issues, that would get pregnant easily otherwise), but society has changed a lot concerning childbearing and many women do it late, because of social pressure and many times are unsatisfied with motherhood. Again we think that we have to assume that not everybody is willing to reproduce like rabbits.
And that next pandemics may not hit the elderly only.
Everything you are saying about female education and motherhood is well known and accepted, and I take no issue with it. But the key point is that regardless of reduced fertility, there is a significant lag during which population rockets. This is evident in many developing countries. It does not matter in the short term that women's fertility drops, because it does not drop as fast as childhood deaths do. I see something similar happening with civilisation after aging is solved. There will be a decade or two whilst it is being rolled out and everyone realises that there is no longer a time limit on motherhood. In that time population will go up. It is another discussion whether we are really about to solve aging or whether it will take another 100 years. But I think we need to have the discussion before it is upon us.
Perhaps the microbiome is the clock? A new paper.
"Here, however, by comparing gene expression profiling of Drosophila raised either conventionally, or free of bacteria, we show that ∼70% of these conserved, age-associated changes in gene expression fail to occur in germ-free flies. Among the processes that fail to show time-dependent change under germ-free conditions are two aging features that are observed across phylogeny, declining expression of stress response genes and increasing expression of innate immune genes. These comprise adaptive strategies the organism uses to respond to bacteria, rather than being inevitable components of age-dependent decline. "
https://www.sciencedirect.com/science/article/pii/S2589004221006714
The capacity to show "Adaptive responses" is programmed in the genome.
Almost all body physiology is Programmed in the genome. We call itHomeostasis (regulation) without which we will be deade like "non prigrammed chairs" (the one obeying wear ant tear necessarily wrong "theories" (just wrong hypotheses) of evolutionary aging.
Such programmed regulation wiil be also responsible for ourcapacity to live for 1,000 years (at mininum) in the future. If cells renew themselves continuously (turnover that chairs do not have) why not we live indifinitely?
Because some of the programed regulations include the determination od spexies-specific life span. That s why sckentist must study the nucleus of neurons, cardiomyocytes and sk. muscle cells, the ones most important for aging. Biology knows almost nothing about the functioning of those nuclei. Almost all mother cells stem cells etc and similar wrong approaches (in fashion) to aging are done in very diffrent cultivated cells like fibroblasts which mislead the researchers.
PLEASE LOOK AT THE NUCLEUS OF THE POSTMITOTIC CELLS! (just in case you know how to do that, much more difficult than population doublings etc
Josh posted comments and even received a reply on my comment but they can not be seen here. Can please you look into this?
If you click on "reply" on any post, it will reveal all hidden posts. It doesn't really fix the problem, but it works.
The inevitability of aging does not exclude that temporarily rejuvenation is not possible but only temporarily. These old rats turned into young rats only
temporarily. After 1 year (if not dead) the rats would be older.
It is the same as with the entropy. The entropy of a system could be decreased only temporarily with the intervention from outside.
Besides this, the rejuvenation of the rats was measured using only physiological parameters.
I am 58 years old and I've done one year ago a complete medical check (130 tests !). The biological age that resulted from that tests was 39 years.
But I do not feel, by far, like when I was 39 years old. At most like when I was 50.
So what's the use that a 90 years old man have the biological parameters of a 50 years old when he feels as at most 75?
It's funny to me when people tout their "biological age" from these aging clock tests when they actually look much closer to their chronological age. I do think these testing methodologies are likely misleading and inaccurate.
Florentin: I am agreeing with your post just in case that did not come across in my prior comment.
Florentin. I agree with you except for one detail: we animals are energetically OPEN systems. That's why our entropy does not have NECCESARILY to increase AT ALL. Aging is not due to "entropy". That is tru of chairs and other innanimate objects. Not of living things that co tinuously ingest foid (energy) and use it to autoorganize ourselves. If there is aging in spite of this fact is because we the animals produce aging internally on purpose to age at a speed tipical of each species. Forget ablut "entropy" when discussing animal aging.
Florentin - I ask you to be more specific about the word "temporarily". There are clams that live 500 years. There are redwoods that are 3000 years old. There are Aspen groves, grown from a single seed, that have continued to propagate through underground root systems for 30,000 years. All these living things have managed to "temporarily" avoid aging.
If all that you mean is that we will all die evenutally, I agree. Nothing lasts forever. If I live long enough, I will die in a traffic accident. The earth will be engulfed by the sun as a Red Giant. All life is temporary. Stars and even galaxies don't last forever. Black holes evaporate in a googol years.
And humans couldn’t fly, until they built airplanes . Longevity technology is coming fast, like it or not, and the rest we’ll just have to figure out.