The Mistaken Belief that Rejuvenation Therapies Will Not Arrive in our Lifetimes
If you ask those who are skeptical, disinterested, or even hostile towards work on the basis for rejuvenation therapies, many of them justify their positions with - among other items - a belief that rejuvenation is a far future possibility, not something that will arrive in their lifetimes. So why should they offer their support, given that they will not benefit? They'd rather leave it to the slow march of science, which most people seem to think just happens, a background process that runs without any outside intervention.
Firstly, this is a dramatically mistaken point of view. The first of the SENS-style rejuvenation therapies, the clearance of senescent cells, is presently in the clinical development pipeline in a number of startup companies. Forms of treatment will be available a few years from now via medical tourism, and the adventurous can already obtain many of the candidate drugs and try their own self-experimentation. The first class of rejuvenation therapy is imminent, not distant.
Secondly, even if it were true that rejuvenation is long way distant, why not help to build the infrastructure for a better world that will carry forward into a future that you expect not to be around for? People do that all the time in other parts of their lives, without the same sort of vocal rejection that all too frequently accompanies views on healthy life extension, a goal to be achieved through new medicine to treat the causes of aging. Why should longevity be any different? I think that this is another of the many ways in which people demonstrate a strange irrationality when it comes to aging and medicine.
This is what I call a 'meta-objection', because it's not really meant against rejuvenation per se. Rather, this meta-objection is usually raised after a long, drawn-out conversation between a rejuvenation advocate and an opposer. At the end of the debate, when the suspicion that rejuvenation is in fact desirable and may be feasible is starting to creep up into the opponent's mind, they resort to their final, desperate line of defence, the very last stronghold behind which their cognitive ease can still find shelter. If we all thought like that, no one would do anything to make rejuvenation happen, and consequently it would never happen, in anyone's lifetime, ever. We can either risk it and do all that is in our power to make rejuvenation happen sooner rather than later, or we can sit about and wait to become old and sick.
Besides, if rejuvenation is worthy goal per se, should you not help pursue it just because you might not reap the benefits? We hear all the time that we should take good care of the planet for the sake of future generations and be concerned about the kind of world we leave them with. Well, we can try to leave them with a world where ageing has been cured, so that those very future generations we seem to care so deeply about won't have to go through the plague of age-related diseases. If you have children, this should resonate particularly well with you. Old or young, they'll always be your children, and you'll always care for them, right? Without rejuvenation, they too will be condemned to decades of infirmity and suffering, and ultimately to an unnecessary death.
If rejuvenation could be achievable within the opposer's lifetime, they would have a glimmer of hope to hang on. And as they say, isn't it hope that kills us all? If they decided to accept this possibility, it would mean a lot of mental work, of the kind people generally dislike. First, there's the risk of disappointment. What if something went wrong, and rejuvenation didn't come in time for the opposer? They'd have spent a life hoping for something that never came. The thought isn't particularly nice. Second, there's a choice to be made between activism and 'inactivism'. In order for rejuvenation to become real, there's a lot of work to be done, not only in terms of research but also advocacy. Would the opposer be willing to do their part and spread the word, convince others of the worthiness of the cause, and take action to make it happen sooner? That's a lot of work, and there's no guarantee of success. They'd have to endure endless debates with sceptics, which could be quite taxing.
This is not all! Accepting the possibility that rejuvenation may become a thing within their own life, and that they may actually want it for themselves, the opposer is forced to seriously question their previous assumptions on ageing. This idea that ageing is bad for you and not desirable is a new thing, one they're not used to. They're used to accepting ageing, to think of it as a blessing that prevents the (imaginary) risks of eternal boredom, overpopulation, everliving tyrants, and a series of other sensible-sounding, but ultimately groundless excuses we've made up throughout history to cope with the sad truth of the grim descent into frailty, disability, and disease that precedes death. If they challenged their old assumptions on ageing, the opposer would be forced to conclude that ageing is a really bad thing - and what's worse, that really bad thing is coming for them, and their chances to avoid it are tied to a technology that may or may not come into existence depending not only on the progress of science, but also largely on how willing other opposers will be to challenge their own preconceptions on ageing.
This is where our opposer comes to the realisation that he or she would have to deal with all this trouble only if rejuvenation could happen within their own lifetime. If rejuvenation was so far into the future that the opposer was granted to die before they could ever benefit from it, all of these troubles would just disappear. 'Yes,' the opposer would say, 'maybe defeating ageing is feasible and perhaps even desirable, but it's not doable within my lifetime. So, there's no need to concern myself with it.' It's so easy, isn't it? The easiest way of 'solving' a problem is pretending it isn't there to begin with. You can keep repeating to yourself all the lies about why ageing would be a good thing, until - as it's often the case - they start to feel true and make you feel good.
Rejuvenation is definitely closer than people think.
http://www.cell.com/cell/fulltext/S0092-8674(17)30246-5
"Moreover, it restored fitness, fur density, and renal function in both fast aging XpdTTD/TTD and naturally aged mice. Thus, therapeutic targeting of senescent cells is feasible under conditions where loss of health has already occurred, and in doing so tissue homeostasis can effectively be restored."
Mainstream papers like these basically admit we've achieved functional anti-aging (albeit partial) in an animal. This kind of language would have been impossible even 5 years ago. So the science is progressing faster than most people think.
I'm not entirely sure if the problem isn't a philosophical one though. I feel like they use the "it won't be here for us" argument mostly as a cherry on top rather than an actual argument. It's what they consider the discussion ender, rather than an opener. So in most cases you would have to debate their previous arguments first.
"the sad truth of the grim descent into frailty, disability, and disease that precedes death."
Gee, sounds awful. Except that it is not true, for people who take care of themselves. Jack LaLanne did not face a "grim descent into frailty, disability and disease". He just up and died, one day. It is called squaring the curve, and it is a good idea.
@alan2102 Unfortunately it is absolutely the truth.
Jack LaLanne was not in any way shape or form fit at the time of his death, or even in his 70s.
He was fitter than most and that is great, BUT his fitness is to a great degree a result of "good" genetics. Something most people do not posses. My grandfather used to chop firewood and work well into his late 70s as well, still I wouldn't call him fit. End of life disability is nominal - LaLanne simply lived longer than most people and his disability was moved down the chronological line.
Also I'd like to point out that so far we've had a lot of experimental success with making animals live longer, but they still have their nominal period of disability at the end of their lifespan, if they didn't - they wouldn't die. Healthy animals do not die.
The whole squaring the curve idea came about from experiments with species so short lived their period of disability can look like a square. Unless you zoom in.
Apart from what Anonymoose said, a single datum is a very poor statistics. There is very solid, statistical data about fraility in old age, and it's a general, non-preventable phenomenon. See for example https://www.fightaging.org/archives/2015/08/more-life-less-severe-illness-but-more-years-of-illness/
See also:
https://www.fightaging.org/archives/2015/12/the-muscles-of-old-still-active-athletes-are-as-aged-as-those-of-non-athletes/
Also, if you want to play the single-datum game, Jeanne Calment smoke from age 21 to age 117 ;)
The hell with squaring the curve quality and quantity is the aim of rejuvenation biotechnology, I am not interesting in the goal of just healthspan that is for the conservative appeasers.
My father was a very healthy 81 walking 3 miles a day and doing light chores. I a healthy 50 yr old said that I would be happy to live to 81 in a healthy manner like him. He said tell me that when you are 80 son.
@Gerard Morton Most people in my family were healthy in their early 80s. As in - healthy for 80 year olds - the paradigm that has been pushed unto our culture that there is healthy - the healthy of people up to their 40s and then there's the "healthy" for the people above that age. And THEN there's the """""healthy""""" of people above 70.
If you have a heart to heart conversation on the topic with these so called "healthy" seniors tho you will get a different picture. Most people don't want to do that. Most people on a subconscious level know the truth. It is a self defense mechanism of the psych, and we understand it well in this community - but we also understand that in the age of advanced biotechnology it is actively undermining everyone's chances to actually be healthy at 80 and not "healthy".
Anonymoose,
I agree with what you said. Same with the expression "Healthy aging" which shows up ever more often and gives me shivers. Aging can never be healthy, and the only way to stay healthy is to stop aging once and for all and reverse signs of aging that have already occured. I'm not interested in healthy aging, I'm interested in not aging.
I'm myself working on stopping it and I will do it. But I'm also happy if SENS gets there first which it probably will. I support it in every way.
@K: Agree 100%. "health span", "healthy aging", "compressed morbidity" have for the last few years surfaced. I'm helping SRF,NO, SOS, OPA and other organisations with my donations and try to see if I can take a new education in biotech and increase my income to donate more. I also tries to help the world getting forward in other ways. Supports other science and technology project. What if ex. Musk Neuralink - all had a chip in our brains how much faster communication could be or if teleport were invented (quantum entanglement), the time we saved could be used to research. Or I support designer babies with higher IQ because we need smart people if aging should be solved! I work to get Norway to be a member of EU which invests more in research and other ways.
@K: "I'm not interested in healthy aging, I'm interested in not aging."
Totally agree, however, as a layman in my 60ties there are just two things I can do right now:
Firstly, financially support SENS Research Foundation.
Secondly, choosing a good lifestyle, a healthy diet, and resistance exercise to buy some more healthy years in the hope to make it until SENS rejuvenation therapies become available.
Bardu, there is a third thing: sign for cryonics.
I am sorry to say, I've been reading about this subject for several months now, and the evidence I've seen that aging can be reversed in humans is zilch. My own impression from reading this very blog is that it will take 20 years for any particular senolytic to be proven safe and effective in humans, and likely for only specific tissue at that. Going overseas sounds too risky for my taste. The most encouraging thing I've seen is Nir Barzilai, M.D. looks incredibly young for his age, and I have to suspect that he is self experimenting with something. All the other scientists publicly speaking about this subject look their age. I feel it is going to be sad seeing Aubrey grow older. I would like to see him stop hiding his age with his beard that covers his face. I hope that I am wrong.
@NY2LA, well if you're 20 years old maybe you can wait another 20 years for senolytic and other treatments to be proven 100% safe. Even the Australian researcher who conducted the latest study into senescent cell clearance stated that these therapies would be available in 5 years time. The only thing I know is that I'm 46 and aging certainly isn't safe for me.
@NY2LA: What evidence, specifically?
I mean, what parts of this blog made you think that there is no evidence that aging can be reversed in humans? That's a very strong claim, since aging has been reversed in mice.
@NY2LA A lot of people already self experiment with senolytics in my knowledge. There are approved and tested drugs with a known senolytic action - and they use those, for all intents and purposes those are safe drugs, they've passed a rigorous testing process.
If we're talking about drugs specifically designed for clearing senescent cells like the modified FOX4 peptide in the article I posted in the beginning of the thread, those will take some time to be approved but I believe they can take an accelerated approval path as a cancer treatment and those can take as little as 4 years - which is a long time, but it's not as long as you think it will take by any means.
This is a numbers game - at some point in your lifetime you will have to take the plunge and self experiment, unfortunately we are the first to have access to these technologies and as such we will be guinea pigs to some degree.
At a certain point the possible benefits outweigh the risks. This is the unfortunate reality we exist in.
NY2LA yet another person with a sweeping prediction and absolutely no supporting evidence. Making predictions about rejuvenation being x years away is foolish and so is making statements like "the evidence I've seen that aging can be reversed in humans is zilch.".
There is a mountain of clinical data to support that we can do something about aging and indeed mouse testing (the first step in development) has yielded a great deal of promise for multiple approaches. There is also a myriad of in vitro data with human cells lines. Senolytics is in human clinical trials this year as are a number of other approaches that address an aging hallmark. I see what is happening in the labs and believe me you would be surprised how far we have progressed, just because you dont hear about it doesnt mean we are not busy.
We will be shortly producing a "where are we now?" mega article with clinical status of all damage types on LEAF. This will make it very clear where we are on the roadmap to rejuvenation and will be based on facts not feelings.
@ Anonymoose & K : Yeah... this mantra of « healthy » ageing me be met with a opposite message, both more realistic and more enthusiastic, which is that ageing is hirribly morbid but something can be done about it, so humanity no longer needs self-deception.
@ Norse : You should stay outside of the UE - for your own good.You don't need this awful framework for cooperating efficiently on scientific projects with other countries. Look at Switzerland.
I am 61 years old. My saying it will take 20 years for any particular senolytic to be proven safe and effective is not meant to be a prediction, just a guess based on the fact that use of senolytics looks complicated to me. Research into the metabolic pathway(s) associated with aging is frequently portrayed as complicated, and senescence cell clearance as simple, on this blog. I am suggesting the biology of senescence cell clearance will turn out to be not so simple. And animal models for medical disorders and investigational drugs have severe limitations, so I suspect they do for anti-aging research as well. I am looking forward to senolytic human clinical trial results. They will hopefully provide the evidence that I am looking for, and sooner than I am anticipating.
Hello NY2LA:
"My saying it will take 20 years for any particular senolytic to be proven safe and effective"
Clinical trials never take 20 years to conclude. At most, they take 8-10 years. I don't think trials for senolytics will take more than 5 years. Senolytics act quite quickly in mice and human cell cultures, and the end point is easy to asses for human trials. It's not like cancer, where you need to wait to see the 5-year survival rate, due to cancer relapse.
"just a guess based on the fact that use of senolytics looks complicated to me"
That's not a fact, that's an opinion.
"I am suggesting the biology of senescence cell clearance will turn out to be not so simple."
Based on what?
"And animal models for medical disorders and investigational drugs have severe limitations, so I suspect they do for anti-aging research as well."
That happens because those drugs try to modify the metabolism, and human and mice metabolism are different. Senolytics don't try to do that, only to kill some cells. And anyway, differences between mice and humans don't make trials to be prolonged for 20 years. Those trials simply fail, in most cases in phase I.
"A Perspective on Clinical Translation of Senolytic Drugs" posted on this blog on April 20 was the clincher at making me believe use of senolytic drugs is complicated, typical of all biological processes. The paper referred to in that post reveals how much we don't know about senolytics yet. My impression of cancer trials is they are usually done on people who have nothing to loose because their condition is terminal, hence greater risk taking is merited. They weren't the basis for my 20 year estimate. I am including pre clinical studies in my 20 year estimate for senolytics because I don't know of any senolytics in Phase I yet. Of course, this is all just my opinion.
"I am including pre clinical studies in my 20 year estimate for senolytics because I don't know of any senolytics in Phase I yet."
There are several senolytics that already passed the preclinical phase, so your claim that any senolytic drug trial will take at least 20 years can't be true unless clinical phases take 20 years.
The article says that current assays don't detect all senescent cells and current candidates don't kill all senescent cells. But that doesn't mean that the candidates will not have a significant therapeutical effect or that the effect will be difficult to measure to a significant extent. We don't need to kill all the senescent cells to have an important effect in aging and age-related diseases, nor do we need to exactly meassure the amount of senescent cells in order to show that a drug is beneficial.
This is a general principle for damage-repair therapies. We don't need full understanding to do something about age-related diseases. SENS is based on bypassing that lack of knowledge.
About the endpoints mentioned in the article, current senolytic drug candidates entering clinical trials will not be tested for endpoints based on healthspan or lifespan. They will target specific diseases like osteoarthritis.
"This is a general principle for damage-repair therapies. We don't need full understanding to do something about age-related diseases. SENS is based on bypassing that lack of knowledge."
I've read this basic principle many times on this blog. I fail to see proof that it is this simple. I suspect as clinical trials progress, it will turn out to be much more complicated than this general principle makes it out to be.
Tocotrienols + Quercetin
Are there more recent information available about those compounds than described here:
http://www.lifeextension.com/Magazine/2016/10/Natural-Compounds-that-Remove-Aging-Cells/Page-01
"I've read this basic principle many times on this blog. I fail to see proof that it is this simple. I suspect as clinical trials progress, it will turn out to be much more complicated than this general principle makes it out to be."
I has been demonstrated several times. For example:
https://www.fightaging.org/archives/2016/02/25-median-life-extension-in-mice-via-senescent-cell-clearance-unity-biotechnology-founded-to-develop-therapies/
https://www.fightaging.org/archives/2016/12/results-from-the-gensight-biologics-trial-of-nd4-allotopic-expression/
@NY2LA "I suspect as clinical trials progress, it will turn out to be much more complicated than this general principle makes it out to be."
If we're talking about senescent cells specifically - the principle holds in animal models and it will, baring we discover some until now unknown biological difference between mice and men (exceedingly improbable at this point), hold in humans.
Rationally there is no reason why it will not hold true for humans, because we use the same method to fight cancer - cells are malfunctioning, you remove those cells, you get a benefit. In many ways senescent cells are analogous to cancer and some research even points to the conclusion that they are it's precursor - directly or otherwise.
We are going to reap the benefits of decades of cancer research - our methods of targeted removal of cells are progressively getting better so there will be minimal side effects. And in turn cancer research is going to reap the benefit of research into aging because we will have a universal prophylactic treatment against cancer (among other age related disease) and also a method of making the side effects of more aggressive chemo milder.
In my personal opinion any approved senolytic whether it is in a normal trial or an accelerated one - you're better of trying it once you're pass your 70th birthday. Some people drink and smoke their wholes lives, worst case scenario you'll still be better off than them.
Thank you, Antonio, Anonymous, Steve, et. al. I'm more optimistic now.
Just pilling onto the theories of why people don't take action to support aging research. I think there is also a free rider problem. Some people figure that something might be possible but other people will probably take care of it saving them the sacrifice.