The Wrong Inflection Point in Aging Research

While it is still a small field in comparison to much of biotechnology and medicine, research into slowing and reversing the aging process has achieved legitimacy and growth in the past decade. This newfound capacity for progress results from a great deal of work by patient advocates, visionary researchers, and other allies to overcome public disinterest and a hostile leadership in the field of gerontology.

Sadly, most participants in the now energized research and development communities are pursuing varieties of a poor strategy, often called geroscience. They have taken the wrong realization regarding the plasticity of aging, and are working on lines of development that are unlikely to produce large effects on human life span. This work descends from the earliest and best supported modern investigations of aging interventions. It involves the search for longevity-related genes, near all of which manipulate stress response systems (such as autophagy) that can slow aging in short lived animals. Calorie restriction research is one of the major areas of work, but there are numerous others that touch on ways to make animal metabolism more optimal for longevity than is the case in the wild.

Unfortunately, we already have all the evidence we need to show that these systems of cellular maintenance - activated by stresses such as starvation, cold, heat, and toxins - have comparatively small effects on longevity in long-lived species. Calorie restriction extends life by up to 40% in mice, but it certainly doesn't add more than a few years in humans. Further, the practice of calorie restriction cannot greatly reverse the state of aging once it has occurred. It is very much a case of better than nothing, but not a road to dramatic rejuvenation or lengthening of life.

Some people see the uptake of interest in aging research and the building of a longevity industry, and feel justified in saying that an inflection point has passed. That is the case in today's open access paper, quoted below. The real inflection point still lies ahead, however, in the adoption of a truly viable strategy to produce human rejuvenation - a strategy based on damage repair that is quite different from the majority of present work on aging. This inflection point will occur when significant portions of the research community buckle down to work on repairing the molecular damage that causes aging, rather than tinkering with metabolism to slightly slow down the accumulation of that damage. This transition has yet to happen. Until it does, progress will be marginal.

From discoveries in ageing research to therapeutics for healthy ageing

The rapid increase in our understanding of the molecular mechanisms that underlie ageing has created new opportunities to intervene in the ageing process. Two notable findings have emerged from these early studies. First, the number of genes that can extend lifespan is much larger than expected, which suggests a much higher level of plasticity in the ageing process than expected. Second, genes that control ageing - which define cellular pathways such as the TOR and insulin signalling pathways - are remarkably conserved in yeast, worms, fruit flies and humans. The conservation of these pathways across wide evolutionary distances and the fact that targeting these pathways in model organisms increases both lifespan and healthspan has brought to the fore the idea of interventions in humans.

Rapidly ageing societies across the world are seeing an increasing healthcare burden attributable to both morbidity and cost of age-related diseases, such as heart disease, stroke, cancer, neurodegeneration, osteoarthritis, and macular degeneration. However, current medical care is highly segmented as well as organ- and disease-based, and ignores the fact that age and the ageing process are the strongest risk factor for each of these diseases. According to the concept of geroscience, targeting conserved ageing pathways is anticipated to protect against multiple diseases and represents a different approach to tackling the rapidly growing burden of diseases worldwide.

The concept of geroscience predicts that conserved ageing pathways are part of the pathophysiology of many age-related conditions and diseases. For example, multimorbidity is seen as the multisystem expression of an advanced stage of ageing rather than a coincidence of unrelated diseases. Targeting conserved ageing pathways should, therefore, prevent or ameliorate multiple clinical problems. This hypothesis remains to be tested in clinical trials, but is supported by several lines of evidence. A wide range of animal models of specific diseases can be affected by manipulating a single ageing mechanism (such as NAD+) or senescent cells in the laboratory. Rates of individual age-related diseases and of multimorbidity increase nonlinearly with age, and the rate of acquiring new chronic diseases may be higher in people who have an existing chronic disease.

We are now entering an exciting era for research on ageing. This era holds unprecedented promise for increasing human healthspan: preventing, delaying or - in some cases - reversing many of the pathologies of ageing based on new scientific discoveries. Whether this era promises to increase the maximum life span of humans remains an open question. What is clear is that, 30 years after the fundamental discoveries that link unique genes to ageing, a solid foundation has been built and clinical trials that directly target the ageing process are being initiated. Although considerable difficulties can be expected as we translate this research to humans, the potential rewards in terms of healthy ageing far outweigh the risks.

Comments

While I agree that an inflection point is being reached, I can't help but feel that existential risks to humanity are much more likely to kill most of us than aging is. Yes, aging causes a lot of suffering, but I would argue that what's going on right now is indicative that the amount of relatively small amount money devoted to the problem is appropriate.

We should be concentrating on saving humanity, and making life worth living while doing that. This is not going to be the last pandemic; terrorists are going to create much more lethal viruses when that technology becomes available. There's even a small chance that there will be one after another, if the ability to create viruses outpaces the ability to create vaccines, and that we may look back five years from now at this week being the last time that people were able to gather together in big stadiums.

We need to deal with bigger problems first - superintelligence, nanotechnology, and pandemics. The problem of aging is minor in comparison to these issues.

Posted by: Steve Sokolowski at March 13th, 2020 3:01 PM

@Steve Sokolowski

You are right that existential problems are more important. But let's not pile every bad news of the day on the existential wagon.

Just to give some sense of perspective.

Terrorist attacks are bad. (quick google search lead me to this quote "In 2017, terrorism was responsible for 0.05% of global deaths." - about 26K ) Bad but hardly species threatening . In fact each ear in US alone more people die from flu complications than in the whole world from terrorism.

Wars are much worse. The most recent big war (Congo is estimated to some 4 million deaths) and a full-blown nuclear war can be species or at least civilization threatening.

Dying of old age and associated disease is easily a couple of millions in US every year.

Estimate of possible deaths caused by corona virus "As many as 200,000 to 1.7 million people could die." Most of those are already elderly.

Posted by: cuberat at March 13th, 2020 6:07 PM

@Steve Sokolowski
I disagree about whether many of the risks people point to as existential threats are really worthy of the same level of resources as aging, but regardless of that argument (which we aren't going to have in FA comments), you are ***way*** off the mark to suggest that the small amount of money devoted to aging is in any way appropriate. It's fairly clear at this point that the structure of the healthcare system and current NIH budgeting that devotes so large a fraction of money & research to fixing chronic age-related diseases long after aging has made them all but inevitable in highly inefficient and inappropriate. The faster resources devoted to health are diverted away from the existing chronic disease silo model and towards the underlying molecular pathology of aging the more lives will be saved.

Posted by: Karl Pfleger at March 13th, 2020 10:22 PM

Eliminating aging is more important, because it's the only thing that's guaranteed to kill everyone.

Posted by: Florin at March 13th, 2020 11:24 PM

I'm also worried about this wrong headed aging research (the terrorist existential risk is just non-sense, more than 90% of people in the developed world and more than 75% globally die from aging). Aubrey seems more optimist in the last Joe Rogan show, a couple of weeks ago, predicting LEV in 17 years and a massive change in public opinion in 3-5 years. But what I see in R+D is still a great percentage of research that falls in the slowing-aging camp. Investors seem to simply put their money on all the baskets, hoping that at least a few of them will give them enough ROI. But most of the investors seem to have no clue at all on what line of research should be better.
PS: Thanks for adding an edit function, Reason.

Posted by: Antonio at March 14th, 2020 3:27 AM

Putting aside financial vicissitudes of the last few weeks, repair or slowing of aging is all inflecting downwards as far as investors in these stocks are concerned

Got to keep these people happy or there will be no funds for either

I guess ADG was right when he talked about these companies going public way too early

I mean the entire market cap of AgeX is now less than the spin out fee Mellon payed to BioTime

https://finance.yahoo.com/quote/AGE/community?p=AGE

https://finance.yahoo.com/quote/UBX/community?p=UBX

https://finance.yahoo.com/quote/TORC/community?p=TORC

Posted by: donald dagle at March 14th, 2020 5:32 AM

The Economist had a section this week on genetic medicine and EROOM's law of declining returns on drug R&D (EROOM being MOORE spelt backwards).

https://www.economist.com/technology-quarterly/2020/03/12/new-drugs-are-costly-and-unmet-need-is-growing

The writers pined the cause of this on the fact that ever cheaper genome sequencing means that there are ever more rare congential diseases being discovered.

I was struck by how they largely missed the fact that a lot of the low hanging fruit of infectious diseases were cured in the 20th century, and in the 21st century trying to treat the diseases of aging in the same way, rather than treating aging itself, is the cause of these declining returns.

Senolytics may or may not be the breakthrough that lifts this fog currently hanging over investors and journalists. Removal of oxidized LDL vastly reducing death from heart disease or stroke may be another approach that convinces the wider world.

Posted by: jimofoz at March 14th, 2020 6:21 AM

I understand the comments here about everyone dying of aging, but there are three counterarguments I would offer.

First, aging is not an existential risk to humanity. If it is never cured, people will still continue to live and even thrive, as they have for centuries. A world with people is better than a world with nobody, and it is far more important to prevent a world with nobody from coming about.

Second, as some people still don't seem to understand, this disease isn't just going away in a few weeks. Even if a vaccine is available in a few months (and I think it will be, given that society will be willing to accept less safety testing), it won't be possible to produce enough for another few months with the production capacity we have. Because, in part, Trump cut funding to the agency that was designed to prepare for the issue, nobody will be able to see each other for many months. While having little effect on people like us who comment on the Internet, this change will be jarring for people who get most of their happiness from spending time with others. They would say that life isn't worth living like that if there are repeated pandemics (as I think there may be), so they would not care if they were young or not.

Finally, the economic damage caused by this one incident alone is going to cost at least 1000 times all the money ever spent on aging research in the history of the world. Most likely, a cure for aging, and many other technological developments will be set back by a year as a result of this pandemic.

If we do not do something to be proactive about these threats rather than reactive, we will either all die before we reach old age, or all our resources will be continually spent repairing the damage after each risk is mitigated.

Posted by: Steve Sokolowski at March 14th, 2020 8:22 AM

"Humanity" is not a living being, each person is. Each person is who dies, and in the vast majority of cases he/she dies from aging, after decades of suffering.

And I will not discuss again the coronavirus hysteria. This is not the place for that and anybody really interested in knowing the objective truth can find the data to compare it with much more dangerous diseases like the common flu.

Posted by: Antonio at March 14th, 2020 10:46 AM

I don't like the name inflection point since it applies to analytically defined functions and we don't even have a well agreed metric and even less function. One could argue that anti-aging science took off with the first talk about life actuarial velocity almost 20 years ago , in the sense that rejuvenation is not only a pipe dream which is futile to explore but rather a real, albeit, difficult , distant and ambitious goal. At least there are no theoretical limits like speed of light, or perpetual motion.

The first calorie restriction and fruit fly experiments showed that it is theoretically possible to at least slow down the aging n some species. Senolitics show that some aspects can be reversed. I am surprised that there is so little mainstream interest in senolitics, calorie restriction mimetics and rapamicin. Those are pretty low hanging fruits and if introduced globally can yank a few extra years to the average life expectancy, while reducing morbidity. Probably we need more dramatic effects than weak, albeit statistically significant improvements.

Posted by: Cuberat at March 14th, 2020 12:00 PM

I would certainly agree that this could be deemed as a wrong inflection point. I read this yesterday, and while I was driving around in the car, I couldn't help but think about just how wrong it was - especially once applied to other areas of life and society in dire need of repair.

The first example I thought of, would pertain to crime, specifically, those pertaining to homicide; and the second example went down the same avenue, dark as it may be.

If science only wishes to delay aging, and the death that is inevitably resultant from such, that makes as much sense as having tax payers foot the bill for one year of protective custody for an informant whose life is on contract. We hire multiple agents, for round-the-clock custody and protection, and then a mobile detail that drives around and canvases the area, as well as all of the formalities of getting this person a temporary identity, and food and housing they can no longer pay for due the circumstance that surround them.

So, with that line of logic in mind, how does that pertain to aging, in the context of the wrong inflection point? Paying for a small window of delay, by which the death will inevitably result after a very possible period of suffering, is like putting someone in protective custody for a year or two, rather than taking the hitman off of the streets, and locking up the person who paid for his services. In the end, the result is the same for both the informant and the elderly person - they are both going to die, and there is a great chance it is not going to be quick and pleasant.

In my second scenario, let's consider the murder rate for one of America's most violent cities. Let's put that murder rate at 500 people per year. Imagine if the goal was just to "be modest and measured in our approach", and aim for a 10 to 20% reduction over the course of the next one to two decades. Sure, an improvement is an improvement, but we are still talking about 400 people getting shot, even after 20 years of working on it. Between now and that 20 year target, the suffering and loss is horrific.

This is the mindset-parallel of the wrong inflection point. The correct way, which is much like that of SENS, is to identify the problem, and the multitude of factors contributing to it, and to aim to eradicate it as close to a 100% success rate as possible. In either case, whether murder rate or aging, there is a cause, or series of causes, and with that, there will be solutions if given enough continuity in effort.

What is baffling, is that the scientists behind this, however well-intended, and however intelligent, do not believe in the cumulative whole of science itself(and the scientists that are a part of that), as well as the ability to formulate enough hypotheses, to create enough tests, to create enough formulas, to create enough solutions.

Many of these people have some form of tech background, or at least a general understanding, or read enough to soak up trends. Technology, at this stage of the game, is no different than compounding interest in finance. The multiplicative effect is going to become exponential with sufficient time and investment.

$1M invested, in a 10% vehicle, will yield an obvious $100k the first year; but once compounded, year over year, you have more than double your money in less than a decade, and then begin doubling the compounding effect, dollar for dollar, despite no change in investment vehicle rate of compounded percentage.

Same holds true with technology. It is going to get infinitely faster and more efficient, with more and more capabilities, until humans can no longer keep up with machine learning and artificial intelligence, by which time, technology begins programming itself, and does so much more efficiently than humans ever have, creating new languages and new systems and new approaches along the way.

This is a major boon to the sciences. Every ounce of effort invested now, will compound and build upon itself, assisted by the same compounding in technology, and also assisted by the rapid sharing of knowledge that is now leading to the doubling of medical information becoming more and more rapid, in less and less time.

Why is our grand goal to aim for a 10% reduction in the murder rate in two decades, when we can wipe most, or even all of it, out? And why are we paying for a year of protective services, rather than simultaneously going after the contract killer and his financier?

That doesn't make sense, does it? So then why are we only aiming to do the same with suffering at the hands of time and biology, when there will inevitably be solutions for that also?

No matter the case, in all of these examples, the end result is death, and likely, suffering as well.

What ever happened to "Shoot for the moon, and even if you miss, you will still be among the stars"? Why are we looking at aging with a rubber band, and thinking, "Shoot for the ceiling just above my head, and even if I miss, hopefully it will land on someone's desk"?

Electricity did not exist before someone took on the challenge, nor did flight, nor the automobile, nor the phone, nor the oven, nor any other of our modern conveniences and "necessities". All of these were met by skeptics, and none of these would have existed if the great minds behind them settled for a ho-hum mediocre, 10%, shoot the rubber band at the ceiling approach.

The right inflection point is critical - and the creativity, thought process and mindset going into it, and envisioning it, is what will eventually produce the grand desired result, or will resign itself to be the byproduct of cognitive limitation directed by insufficient belief to go much beyond the current realm of the tangible.

Adding briefly to that, if one is to examine any number of trends over the course of human evolution, this makes little sense, seeing as the tangible is nearly always the successor of the intangible. Fire didn't exist before it existed. Vision is the predecessor of what becomes the visual. If we can "see" it, will eventually see it. It's pretty important we make sure our lenses are the right prescription.

Posted by: Adam at March 14th, 2020 3:12 PM

Well I'm going to disagree with everyone.

Cuberat - I am surprised at you - 'it's just old people' - for shame. You are usually one of the more compassionate (and intelligent) people posting here.

It is true that aging itself is not an existential threat to humanity. The shortsightedness of a species that lives only a few decades IS an ongoing threat to its own continued existence, however.

Seasonal flu has killed more people so far than COVID-19 since it has been around much longer - obviously.

Here's why people should stop trying to compare COVID-19 with seasonal flu:
https://www.youtube.com/watch?v=zjgC41p00Jw

We need to be able to handle more than one problem at a time. Certainly with as many people as there are in the world and with opportunities for learning and collaboration that span the globe, we can.

Posted by: CD at March 14th, 2020 3:38 PM

It is important to note that if "only" 1.7 million people die, it will be solely because extreme measures, far more strict than those taken in America so far, will have successfully contained the virus.

If such measures are not taken, the virus could end up being the greatest catastrophe in the history of the world - definitely surpassing World War II and perhaps approaching the Black Death in the number of dead. Plus, there is now evidence that many of those who do survive have permanent damage to the lungs.

The only reason why the reaction to the virus seems "hysterical" is because an unbelievable disaster would happen if people were not being hysterical about it.

If we are measuring progress in aging by life expectancy, it would be surprising if life expectancy for the average human alive right now is not several years shorter than it was last year. If it was 77 in the US, perhaps it has declined to 74. The life expectancy around 1918 was reduced by 12 years due to the Spanish flu.

As to handling multiple problems, these actions to contain the virus will have taken up so many resources that they will undoubtedly delay humanity's technology by six months or a year compared to if this virus hadn't existed.

Posted by: Steve Sokolowski at March 14th, 2020 3:55 PM

It seems like you're basically asking us to become martyrs for people we will never meet, and we won't even know if their lives will be worth living. And yes, there's a possibility that those people will be able to "resurrect" us by simulation or by some other kind of reconstruction technology, and we'll all live happily ever after in a galaxy-spanning utopia. Or if you buy into empty or open individualism, individuality is an illusion and so we should worry about everyone equally. But all of that could easily be wrong or worse. So, thanks, but no thanks.

Aging has done more damage than all pandemics combined. And relax a little; this particular pandemic is highly unlikely to come anywhere close to 1918. The best estimate of its real death rate is less than 1%.

https://www.sciencenews.org/article/coronavirus-outbreak-diamond-princess-cruise-ship-death-rate
https://samharris.org/podcasts/191-early-thoughts-pandemic/

Posted by: Florin at March 14th, 2020 5:32 PM

I didn't plan to talk again about covid-19 but, since everybody is doing it, I will reply briefly. Here in Spain, worst country in Europe after Italy in number of patients and deceased, we had 190 deaths so far, in around 2 months, from covid-19. Last winter, common flu killed here, in the peak of the flu season, 10,000 people per week. Compare the difference. Around 3 orders of magnitude.

Now, from today, this country is in state of alarm. This was designed to be used for wars, coups d'etat and the like. People here can walk on the street or drive their car only to go to work, buy food, buy medicine, go to the bank or go to the clinic, nothing more. All other movements and activities outside your own house are banned. All bussinesses apart from food selling, medicine selling and other basic needs must be closed for 2 weeks (at least). Police can arrest you and make you pay a fine if you don't obey and walk around for a non-approved reason. And people on the net and around me are surprised that I call this mass hysteria!

Posted by: Antonio at March 14th, 2020 6:34 PM

@CD
Generally, I am cynical altruist. Sometimes more cynical than altruist. I might be even a bit less compassionate than the average good human being. At least a bit, but from bring a sociopath.

This time however, I meant that the bulk of this pandemic will be elderly people, and if their immune system would had been rejuvenated the number of death cases would plummet.

Posted by: Cuberat at March 14th, 2020 6:50 PM

Now , let's don't forget that there are urgent, immediate, important and global problems. And all those categories don't necessarily overlap. A pandemic is urgent and the appropriate actions have to be taken. And if not taken, there cold be grave consequences. But not any close to species threatening. The global GDP will take a hit , for a monthly quarantine will slow the economic activity while it lasts.

But there will be positive effects too. The public health systems will be better adapted to fight respiratory infections, the research on flu and friends will be boosted. Telecommuting and work from home will be forced down the throats of the corporations, and the organisations that successfully embrace it will weather the Corona virus shock. And probably have longer term savings even when the whole story is gone.

Antiaging research might be derailed a bit, there will be some market adjustments (so called "corrections"), research funds will be affected, do there will be some slowdown. But it might be offset by having videoconferences as mainstream practices, which will boost collaboration over distance.

There will be some monumental toilet paper sculptures too.

What you can personally do is to avoid immediate exposure, take vitamins A, E also b, c and d. Avoid taking rapamicin and senolitics. Avoid getting cold.

Posted by: Cuberat at March 14th, 2020 7:38 PM

@jimofoz
You should write in to The Economist: they often take the suggestions of letters from people offering criticisms of their articles, and follow it up with other articles

Posted by: Anonymous Bug at March 14th, 2020 9:54 PM

@Hi Adam! Just a 2 cents.

''No matter the case, in all of these examples, the end result is death, and likely, suffering as well.
What ever happened to "Shoot for the moon, and even if you miss, you will still be among the stars"? Why are we looking at aging with a rubber band, and thinking, "Shoot for the ceiling just above my head, and even if I miss, hopefully it will land on someone's desk"?''

I also asked myself this question several times; I guess it is because we fear failure (happening) (again), it's the old 'low hanging fruit' endeavor, it's simpler and makes money, thus Good...except it isn't. Economically speaking, yes good (for investors), but no, because they die, too, one day, too. Money is an illusion resource and flawed (like captialism model, good capitalism bad capitalism savage capitalism), where the penny goes is where we go (to, live and die of). It's why funding is so low and things have been showen repeateadly to Not stop aging getting funded; because 'sell CR supplements' -> make cash -> good (right?)..except, people still die as you said and still age (and still die). See where I'm going with this, a vicious circle. These analogical examples you gave clearly show that we are being blind continuing this/erring (error) and thinking 'what else can we do...but continue trying (and hoping to not fail) and in the mean time go for stuff that improves health'. But don't talk about curing death/aging people will look you like a martian that tries to predict the future/thinks knows it. There are even 'evil' forces behind all this 'big pharma/CR supplements' that want to continue making cash of your dying body with 'one more pill/prescription'...instead of you know..curing aging/death and be done with it -> no more cash flow because 'people are TOO living' now...they don't die/don't age/don't need all these supplements.

That's a problem (for them).

YOU SEE...how crazy it is...go to doctor, give you a pill...come back...patch work...never Fixing the d*rn cause...and of course, you age during that time...and come back for another pill -> Money making biz.

So bad, money is ephemeral like life, just a temporary resource and then it's gone, like you. Yes, money buys time and time makes money, but you run out of both.

And right now it is the mass COVID19 problem, although some say it is blown out of proportion yet, it is not to be taken lightly neither I think. I think this has to do wit the level of contagion/spreading capability of it; thus 'it can spread all over globe' that is a bit like pandemia.
But, as amny said, this never in 1 second compares to the magnitude that Aging is and the dying it causes; because as said above, it is a certainty for All, if we do Nothing. all of us wil end. 1 day.
of it.

People can survive COVID19..not aging. no one is *mmortal, thus 7 billion people lined up at Grim Reaper door (the number 'on forehead' comes at some point). That. iis scary. For a while, I was at that door, too early, thankfully I escaped him for a lil while.

things are fixable, even aging, but the urgency of it (curing aging) is far more than any pandemia in all humanity history. And in no way am I trying to downplay the severity of this contagious virus happening, it is extremely sad witnessing this (all starting with the Cruise Ships infected...and then like in the old days (colonial past) with plagued ships...they 'brought' the diseases/virus/bacterias all over from the infected ships travellling overseas). It's why every 'port' is blocked to people 'stuck on the ocean' trying to board the ground/port. Right now, the containing/quarantining of it is very important; we can't cure aging/death...if we die early of some virus disease. Priority for that now.

Once things in control (enough let's say) aging must be tackled head on.

I think 'we don't aim for the moon' because was deceived befoer (so many failed studies, it's easier to go 'the easy way'/or abandon a shipwreck and billions of money thrown out the window to defeat cancer...etc...why we would Even Think in a Million Years...we Might Ever Solve Aging..if we can't even solve cancer...or diabètes...etc.. (yet, as you said, miracles happened they were 'long shots - to the moon' thankfull someone tried - but sacrificed themselves for bettermen knowingly or unknowingly by inventing some new invention that saves the world)
That's why. As soon as ADG SENS or other big Company makes LEV in 'some form' (maybe, big maybe, in our lifetime) but in a Real animal not just a few cells here and there...and we apply this to human (probably the first guinea pig humans willing to sacrifice to obtain *mmortal life...a bit like Mrs. Parrish doing TERT Telomerase on herself...a huge leap of faith - for her and her immense sacrifice, helping humanity if indeed we can live longer because person had enough of waiting...and slowly decripting/dying and said 'f*ck it I'm doing it').

Just a 2 c.

Just a 2 cents.

PS: Humans wanted to cured aging since dawn...I remeber Reading a 1850s Something article medical paper about how to stay Young, like this rich man owning a manor back then or Something, and he is like...well I discovered how to stop aging 'sort of' and I tired of taking the 'horse' I want to walk/jog, I'm old..and want to live..so he started doing (I'm not kidding) taking his own fluids (sexual) to make his body youg again and he was like 'I feel invigorated like a 20 year old'....we know that semen contains tons of spermine/sperminidine/cadaverine..polyamines and Ton of stuff (DNA) that slow process, but does not stop aging and actually Lenghtens telomeres (sperm telomeres elongate), but in any case the story ended with we don't know where he went/if he died...nearly 100% sure. But, the point is, huiman been wanting to reverse aging thousand years...not 20 years; it was spoken inancient text, for, ever. Mice that had semen injection in skin saw improvement of skin/rejuvenation and were younber but still died and some developped tumors because of that (blood tumors due to semen); this means that 'high proliferation/division of cells' due to fetal nature of fluid can be double-edged, reverse aging but potential cancer formation (this is the same as Oct Sox Nanog cMyc Ras - 7 day window epigenetic reversal of DNa methyl clock to erase methyl age; but go over that and cancer forms because these genes are oncogenic 'rejuvenation/god' genes that cancer highjack for themselves for extreme proliferation/invasion; they can command telomeres/telomerase to rebuild telomeres or reverse epigenome age; that is reversal of aging/death. But right now it's still a double-edge sword because cancer can be triggered by epigenome dysregulation (wence CpG rich islands become methylated; inversely poor islands become demethylated cause widespread oncogenic preparation/cancer debut and Killing of the host (fight fire with fire/immune system killing you/misbehaving/dysfunctioning trying to destroy cancer and causing Excessive inflammation (SASP/immunosenescence).

Posted by: CANanonymity at March 14th, 2020 9:59 PM

@ale:

What you refer to are deaths from hospitalized people with serious illness and with flu confirmed, but most people that die from flu are not examined for flu and much less autopsied. Most old people that die don't have a proper cause of death written in their death certificate either. I got my numbers from here:

http://vgripe.isciii.es/documentos/20182019/InformesAnuales/Informe_Vigilancia_GRIPE_2018-2019_22julio2019.pdf

The 1,800 number (more precisely, 1,837) is there too (albeit given as 17.5% death rate of people hospitalized with serious illness and flu confirmed (CGHCG), page 6). The 10,000 deaths per week is based on a mathematical model that computes the excess of deaths for flu in the global death rate in Spain (graph on page 23). You can get other numbers from that document too: 115,886 people got infected in the worst week and 833,225 totally, 35,344 people were hospitalized with flu confirmed of which 10,500 were serious (CGHCG), 2,436 needed intensive care and 1,837 died. Efficacy of the vaccine that season (age-adjusted): ~50%. People 65 years or older that were vaccinated: 55.6 %. Deaths avoided among +65 yo by the vaccine: ~20%.

Posted by: Antonio at March 15th, 2020 1:30 AM

Corona virus shows that exponential aging starts at 50.
After 50 death rate is exponentially increasing which means the body is exponentially aging.
Every year after 50 damage will be harder to repair.

Age of Coronavirus Deaths
COVID-19 Fatality Rate by AGE:
80+ years old 14.8%
70-79 years old 8.0%
60-69 years old 3.6%
50-59 years old 1.3%
40-49 years old 0.4%
30-39 years old 0.2%
20-29 years old 0.2%
10-19 years old 0.2%
0-9 years old no fatalities

Posted by: cureNow at March 15th, 2020 6:36 AM

@cureNow
Look carefully. It starts at 40. Just not that bad.

Posted by: Cuberat at March 15th, 2020 7:43 AM

@Cuberat
You are right, it probably starts in the mid 40s.

Posted by: cureNow at March 15th, 2020 8:23 AM

People are also missing that there are now studies demonstrating that the virus causes permanent damage to the lungs in a significant percentage of patients.

I changed my mind about the virus when I read that paper. Originally, I didn't think the virus was that big a deal because death isn't that bad - I would either die, in which case I wouldn't be suffering, or I would recover. But it looks like many people don't recover, and instead have 20-30% diminished lung capacity six weeks later.

This reason alone is why extreme measures should be taken. I'd rather stay inside for 6-12 months than have permanent lung damage that affects me for decades later, and which we will probably discover leads to increased risk of death from flu and other illnesses later on.

Posted by: Steve Sokolowski at March 15th, 2020 8:41 AM

@Antonio thanks for the link but you are misreading that graph. The red, blue and dashed lines that reach 10,000 are showing total mortality for all causes (which makes sense since around 400,000 people die in Spain per year) for a model that calculates expected number of deaths without flu. BTW, the last page of the report (page 35) has a nice summary: 6300 flu deaths attributable to the flu for the year.

Posted by: ale at March 15th, 2020 11:47 AM

@ale: Ah, ok, didn't see that last page, since it was after the references. Then you are right, 10,000 are all-cause deaths. Thanks!

Posted by: Antonio at March 15th, 2020 1:01 PM

Millions of people suffer from reduced lung capacity and die every single year due air pollution caused by the burning of fossil fuels, yet no one seems to be panicking over that catastrophe. And the long-term effects (in years) of COVID-19 is not even known at this point, nor how many of the survivors would be affected.

In case it wasn't clear, COVID-19 is a lot worse than the flu but not as bad as Spanish Flu. COVID-19 likely has a death rate of between 0.5% and 0.7%, the flu has a 0.1% death rate, while Spanish Flu had about a 2.5% death rate.

Posted by: Florin at March 15th, 2020 2:37 PM

@Florin: According to Spanish data, flu mortality rate here was 0.76% last winter.

Posted by: Antonio at March 15th, 2020 3:22 PM

Think how many great minds could be lost to this pandemic.
~~~
The governor of Ohio said a few days ago that they (I'm assuming the state's public health officials) have estimated there to be 100,000 currently infected in the state and the doubling time is 6 days. That means in around 10 days there will be 400,000 cases. It is estimated by all the sources I have read that 20% of cases require hospitalization. There are around 26,000 hospital beds in Ohio.
~~~
Scott & Kubes (2018)* suggest that metformin could be used to treat acute respiratory distress syndrome (ARDS) [what kills in COVID-19, other types of pneumonia, sepsis and so on]. Could it be used prophylactically by older people to prevent development of ARDS should they become infected?

* The article is well worth reading; the description of how neutrophils migrate from sites of injury around the body to the lungs and then - if all goes well - back to the bone marrow to die is truly fascinating:
https://erj.ersjournals.com/content/52/2/1801274.long

Posted by: CD at March 15th, 2020 3:31 PM

"It is estimated by all the sources I have read that 20% of cases require hospitalization."

According to the WHO, 93% of the confirmed cases are mild.

https://www.worldometers.info/coronavirus/coronavirus-cases/

"Think how many great minds could be lost to this pandemic."

Since the vast majority of the deceased are very old, probably most of them had some form of neurodegeneration already.

Posted by: Antonio at March 15th, 2020 3:50 PM

Here's what to do to prevent viral infection:

1. Eat 2 Brazil nuts every day. Buy organic Brazil nuts if possible and keep them refrigerated. Reason: Brazil nuts are extremely rich in selenium and help protect against viral infections and upregulate your body's antioxidant enzymes. [i]
2. Take 1000-2000 mg Vitamin C twice a day
3. Take 3000-5000 IU Vitamin D with Vitamin K daily. These help optimize immune function.
4. Zinc lozenges. These prevent coronavirus from multiplying in your throat. Let dissolve in your mouth if you experience any cold symptoms.
5. Take the peptide THYMOSIN** alpha - 1 (TA-1) daily. It has been shown to increase immune function against viruses. (Bryan note: this specialty compound pharmacy can supply it: Available as daily injection (tiny needle like insulin) or nasal spray. This company offers a sublingual tablet called Immune Peptide, dose is .5mg daily [ii] , [iii]
6. Get nutritional IVs at a local clinic. Consider IV nutritional support such as high dose Vitamin C, Glutathione, B vitamins, Myer's cocktail etc… Every 10 days or so.
[i] From ZRT Labs: How Selenium Protects Against Viral Infections and Mutations
"Adequate selenium nutrition should be considered as a defense against viral infectious diseases. Selenium is an essential micronutrient that is important for immune response, thyroid health, oxidative damage prevention, and many other functions. Selenium from our diet replaces a sulfur atom in the amino acid cysteine to form selenocysteine, which is then incorporated into selenoproteins . There are 25 known selenoproteins, with most of them exhibiting antioxidant properties such as glutathione peroxidase (GPx). Viruses produce reactive oxygen species (ROS) which are combated by GPx and other selenoproteins to slow down viral replication and mutations. Studies using mice have shown that viral symptoms and infection times are more severe when dietary selenium is deficient, and that low selenium intake results in decreased GPx activity. While selenium may not be the only nutrient that 6defense against viral infectious diseases.In a nutshell, selenium deficiency → increased viral oxidative stress/inflammation → increased viral damage and mutations → new viral strains."
[ii] From the compounding pharmacy: "Thymosin Alpha-1 has been known as an excellent immune modulator. Thymosin is a small protein produced naturally by the thymus gland which stimulates the development of disease-fighting T cells. The thymus is an integral part of your immune system, where individual T-cells are made to respond to the millions of bacteria, fungi, or viruses that could invade your body. Commonly prescribed for the treatment for chronic viral diseases, Thymosin Alpha-1 has also been shown to increase innate immunity factors and help fight against harmful autoimmune processes."
[iii] Jing Y et al. Efficacy of thymosin alpha-1 and interferon alpha in treatment of chronic viral hepatitis B: A randomized controlled study. World J Gastroenterol. 2006 Nov 7; 12(41): 6715-6721. In conclusion, the results of this trial indicate that a 6-mo thymosin-α1 therapy is safe and effective in arresting hepatitis B viral replication and reducing lobular activity in patients with chronic hepatitis B.

https://medium.com/@bryan_johnson/covid-19-pandemic-an-exercise-of-human-adaptability-9ca0c5952cab

Posted by: thomas.a at March 15th, 2020 5:42 PM

Looking at the data cureNow has posted above, I'm wondering whether this also reflects how our body's immune system declines while we age?

Posted by: Stephan at March 15th, 2020 8:00 PM

@Florin: Your 80% figure is only from China. The 93% is global.

Posted by: Antonio at March 16th, 2020 3:45 AM

These rational views on global deaths from this or that are okay and very relevant in a community like this. But they are not relevant for the majority of people living in todays pop-culture.

This should be an excellent moment to prop for DRACO and Pulmonary fibrosis reparation. Maybe the people who get really ill would improve if they were given a cocktail of intravenous C-vitamin, melatonin, mitoQ, SkQ1 etc.

Posted by: arren brandt at March 16th, 2020 10:29 AM

Cities and countries are being shut-off. The mere economic shock could probably kill quite a few people even without the accompanying infection. But at least it give us sense of perspective. Just a hundred years ago almost nobody cared about anti-aging because there were so many things that could kill you while still being young. Now we have an infection that by the 19th century standards is nothing to look at and we have a global panic. If only we had working senolytic therapies for the elderly, we could have reduced the virus mortality several fold. Of course, the treated people would live longer and be at even grater danger 10 - 15 years down the road. 10-15 years they don't have now, though. My both parents are highly vulnerable to any acute respiratory infections, so there is good (bad, in fact?) chance that one of them might die in the next couple of months.

p.s.
It looks that a working anti-aging is a solution to almost any problem. Almost like a religion. For most medial issues it surely is. For social and ecological ones it most likely will help too.

Posted by: cuberat at March 16th, 2020 10:49 AM

@arren brandt
Fibrosis and incomplete regeneration should be one of the main priorities. Even a modest improvement there can buy for some people extra years of lifespan .

Luckily, it seems the senolytics can help with that. I hope the study of implanting young mitochondria to be reproduced and verified in humans. That one seems like a low hanging fruit with a lot of potential reward.

As for when the treatments can be available... I remember the promises of e-ink in 2005 to be a tad more expensive than regular paper and to be available in 3-4 years. It took 10 years and while used in e-book readers is not widely used elsewhere . And this is for a technology that has close to 0 regulatory and safety burden....

Posted by: cuberat at March 16th, 2020 11:02 AM

I haven't seen a valid source for the 93% stat. You also mentioned that 20% of cases require hospitalization. That means 80% don't, not 93%.

Posted by: Florin at March 16th, 2020 1:36 PM

We need some way to improve immunity systems now. Older (myself included at 60:() people and sickly included really need help of researchers who can make this happen. I understand it will take multiple years (I hope not more than a decade) but its frustrating seeing yourself vulnerable to things you used to take for granted.

Thus, I wish quick and huge success to Reason's company. This shit (sorry, Reason) may wipe out many older people, very scary:(

Posted by: Robert Church at March 16th, 2020 1:38 PM

@Florin:
Huh? I already posted it, a web page of the WHO. I didn't say 20%, it was you and CD who said 20%.

Posted by: Antonio at March 16th, 2020 3:36 PM

Ah, ok, right. I thought it was from the WHO.

Posted by: Antonio at March 17th, 2020 4:52 AM

I agree with Reason that we should take Dasatinib and Quercetin. Dasatinib looses patent protection in Europe this year (2020) so the cost should fall dramatically possibly $5 per tablet. Genetic modification of our mitochondria so it produces its own NAD+ needs to be pushed forward.

Posted by: Tj Green at March 18th, 2020 9:48 AM

Infection-related illnesses such as pneumonia or influenza is more common in
older individuals, this should be prevented by vaccination. Only 4% of the infected are elderly, , but their mortality rate is 13.5 (in Italy) and 14.4 (in China) of all infected (i.e. 30-60%) of the elderly. It is a pity that no one is now developing methods for rejuvenating the thymus in terms of infection prevention. The delivery of recombinant IL-7 may help to increase the ability of older people to vaccinate and confront against influenza and coronovirus.
Aspinall, R., et al., & Heeney, J. L. (2007). Old rhesus macaques treated with interleukin-7 show increased TREC levels and respond well to influenza vaccination. Rejuvenation research, 10(1), 5-18. doi:10.1089/rej.2006.9098 PMID 17378748
Aspinall, R., & Lang, P. O. (2018). Interventions to restore appropriate immune function in the elderly. Immunity & Ageing, 15(1), 5. doi:10.1186/s12979-017-0111-6 PMC 5785902
Aspinall, R., & Lang, P. O. (2018). Interleukin-7 and Immunorejuvenation
https://www.researchgate.net/profile/Pierre_Olivier_Lang/publication/322751516_Interleukin-7_and_immunorejuvenation/links/5a6d8e94a6fdcc317b182370/Interleukin-7-and-immunorejuvenation.pdf or https://link.springer.com/referenceworkentry/10.1007%2F978-3-319-64597-1_72-1

Posted by: Dmitry Dzhagarov at March 19th, 2020 4:04 PM

The COVID-19 Hysteria plopped the whole world into the laps of the Radical Life Extensionists...

"Never allow a serious crisis to go to waste!"- Rahm Emanuel

Consider that the "Deathist Trance" is a form of mass hysteria we can't control. On the other hand, COVID-19 is also a mass hysteria, but we (Governments and sincere people) currently have it by the short hairs! Albeit a brief window of opportunity exists to take advantage until this pandemic blows over.

Rahm Emanuel was echoed this month by House Majority Whip Rep. James Clyburn, who called the Coronavirus Crisis "a tremendous opportunity to restructure things to fit our vision." Don't we here at FA have a vision!?

With death and suffering from COVID-19 all around, billions of souls across the whole of planet Earth are in a new frame of mind about death and disease because the game has changed. Their lives may be in peril, and the old way of life is suspended in many ways too numerous to enumerate.

One school of thought would say that the world will go back to the "same old, same old" when this coronavirus ordeal is over. My thinking is that a world focusing their attention on the matter of death and disease (COVID-19) may be ripe for a pivot to: bearing down on the diseases of aging and the death that consumes all eventually - guaranteed! - as sure as COVID-19 can kill!

Engineering negligible senescence is the answer.

Employ 1 trillion dollars to fund ADG's SENS "Manhattan Project" to solve the problem in this milieu of trillions being given out like candy.

Millions of people will have employment. Factories will retool for our new bio-tech industry, like they are for COVID-19. We can return to prosperity and the world will be a healthier and happier place. UBI could provide a financial buffer solution for many people as we transition into our new economy.

This is my vision and I realize there are many details to fill in. Will anyone entertain this munificent possibility?

Sincerely

Frank Rummel

Posted by: Frank Rummel at March 29th, 2020 1:47 PM

@Frank Rummel: Knowing the general public and the politicians, I think that what will happen will be very different. Instead of a boost to aging research, there will be a boost to infectious disease research. Thus, basically the situation will be the same as before: the cause of more than 90% of deaths will continue to be neglected and most of the effort will go to the less than 1% that is caused by infections.

Posted by: Antonio at April 14th, 2020 12:16 PM
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