Fight Aging!

I have been commenting on this forum for more than a decade and while I used to be optimistic about the prospects for radical rejuvenation in my lifetime (I am in my early 40s), I have become much more negative over the past couple of years.
At the cost of appearing troll-ish, here's why:
1) The vast majority of interventions that could potentially resolve what goes wrong with aging (epigenetic alterations, loss of proteostasis, telomere attrition etc.) are still at the preclinical stage. It takes 15 years from preclinical to market.
2) Who's to say that successes in mice will translate into successes in humans? Only a tiny fraction of drugs that work in animal models are eventually approved.
3) Even if a drug is approved, who's to say that it will have a radical benefit? To be approved, a drug doesn't need to fix a problem but only to be better than standard treatment. And for the vast majority of the issues we need to fix to cure aging there is currently no treatment, or the treatments we have are almost useless. Just look at cancer drugs: what's hailed as a "breakthrough" is something that extends life by a few months.
I am sure that eventually we will get aging under medical control, but for the life of me I cannot see how this could happen in 15 years, as de Grey and perhaps others have been saying.
For this to happen, all or almost all of the treatments currently at the preclinical stage must be approved and each must do far better than add a couple of months to life expectancy.
I agree that in 15 years time we will live longer, but to say that people will be able to live for however long they want is beyond silly. Pushing up life expectancy from 80 to 85 or even 90 won't buy anyone who isn't very young today enough time for new treatments to buy them more time because at older ages the risk of death increases way faster than the pace of drug discovery.

@Barbara T.:

I understand where you are coming from. When we look back at how long we have been working on human rejuvenation and how little we have achieved, it can be disheartening. However, I do think there is reason for some level of optimism. The main thing is that the speed at which this or any field moves is directly related to the technology that is available to support it. If we freeze the current technology, then indeed, although the field would continue to progress at the current rate, it wouldn't be enough to achieve LEV for a very, very long time, if ever. But, the technology does continue to evolve, and at a very rapid exponential rate.

i) First of all, computational power per dollar grows something at something like a 1000 fold every 20 years. The importance of this is multifold. The obvious use is to model biological systems. This is valid, but will depend on having the relevant experimental data. So, it isn't enough on its own. Computers are also extremely important in the design and development of other tools. As the computers improve, so will the tools that we use to study, analyze, measure, and modify biological systems. Also, as computational power improves, AI improves along with it. We can already see gigantic strides in this area with achievements such as AlphaFold and now Gato. As AI becomes more powerful, it will also help model systems and build better tools. This one is quite powerful and will have an exponential influence on this field in the decades to come.

ii) Nanotechnology also continues to improve at an exponential rate. They are building more and more sophisticated molecules and moving towards molecular machines. It is hard to overstate the importance of this as it rapidly grows. In 20 years, it is very hard to imagine that this field has not taken a much larger role in rejuvenation, making measurements and manipulations possible that we can hardly imagine now. At some point, they will begin succeeding at building machines the size of cells that can move through our bodies and fix problems. I don't know whether that will be in the next 20 years, but it can't be 100 years. It is improving way too rapidly for that and it would require some sort of totalitarian imposition to stop its progress.

iii) 3D Printing. The sophistication continues to evolve at an exponential rate. I am blown away by how much progress they are making. In 20 years, it is hard to imagine this not being much more important in rejuvenation. For one thing, we can imagine bypassing tests on mice altogether and testing directly on 3D printed tissues of ever increasing sophistication. Not only could we bypass mice, but we might reduce the number of clinical trials necessary if we can already prove some level of safety and efficacy in 3D printed systems of tissues and organs.

The important point here is that the technology that support rejuvenation research is improving at an exponential rate, not a linear rate. The next 20 years will see much, much more improvement than the last 20 years.

This does not convince me that it will be in time for me (I am in my late 40s and am pretty healthy). Even if we achieve LEV as a society in our lifetime, that does not mean that every individual will achieve LEV. There are too many unknowns on the individual level still. I also do not know whether societal LEV is 15 years away of 20 or 30... But, it is coming and I don't think it is 100 years away.

barbara, you are not optimistic -- but you are realistic.
some treatments against aging will very likely be available in the next 5 to 10 years but it will not be a complete cure of aging. Humans receiving those future anti-aging treatments will age slower and live a little longer than the average human today, they will still die of aging.
but don't be discouraged : continue fighting against aging process no matter how long you live .....
....to the bitter end.

Hi Barbara! Just a 2 cents. TL DR: we can't...stop (to hope); I mean we can just 'forget it all'..abandon the prospect of rejuvenation...make a Big X on it...and just 'live in hedonistic life'...for the remainder of our life years....but, then we can also not do that and say: 'no. I want to live and I'm doing stuff Right Now...so that Later..I might get a few months extra of life or health or whatever --...I'll still take them..I'm a taker. As 'so not worth it' it looks; I still will believe and will still hope and will take - Any - thing''.

I feel the same/way; sometimes I think to myself..... why bother? ...then I think to myself...''because you must...if you don't bother anymore...you are one foot (away from/) in the grave''. It's like breathing...we can't stop breathing : ''why do I Have to breathe...I don't want to breathe...''.; I guess, we can't stop - hoping, and not bother anymore/abandon in defeat...
fightaging.org ---------> defeatedbyaging.org / losthopeagainsthisfightforlife.org

if we abandon (hope), then it is 100% - assured/fact, we will never reach the big 150-200 etc...

It's normal (as others said)...to feel down about it and very pessimistic; realistic...about it..thus, a healthy does of pessimism (because it failed in the past decades...so why would it magically change...in say the next 15 years...most likely, nothing will have changed, if much, that is 'substantial/Tangible');

It's like an illusion/oasis mirage dream...progress does advance and you 'get closer to the oasis'..but, actually, the oasis is Still far& we still misjudge/miscalculate its distance,.it's farth-Er...
and even, Receding- as we approach it...a 'catch'.. talk about demoralizing; it's like building a monument - to 99.5% complete; then abandonning it at 99.6%, to let degrade itself/demolish it -- because, could not reach the big 100.0% - 100/100. It is called 'scope creep'; where the project is so big..that as time goes - it Grows...'Snowballs'...like a snowballl growing and growing as it rolls down the snow hill...we thought the ball would stop growing and we would 'finish'...but, it's the inverse; it keeps 'growing' as time goes; and thus, the 'Finish Line'...'pushes away/farther' away..we are 1 inch closer -- but the finish line has receded in the background by a 1000 mile.
old saying:
''work expands as time goes - and fills it''.

And now, with Big Pharma...it's problematic..because big pharma wants to 'keep making money from your dying body - prescription and pills...and you come back for more'....wants you (just) 'sick enough' to make the money train roll...
Defeating aging and health problems...solves this. But that's a 'problem'...(for pharma that is --no more money when people are 'too healthy/living too long').
But, as you said, the biggest problem is the Time it takes is vetry long...15 years for arriving onthe market...just wayy too much human lifespan - we only have 120 - at the best of the best.
Bureaucratic red tape/nightmare is the large cause too...but, you also pointed the other problem,
with minimal effects or 'big effects' in mice that translate (in any case/anyway..) as basically no effects in already long-lived humans..

I agree that progress is advancing rapidly...but there is a illusion...like a 'stand still'...or doing 'on place/parked' on same spot'...not Really advancing; or not enough. It's like that it's (very) Baby steps, 1 babystep at a time. We should? get there..hopefully, we won't be 115 when that happens (we most likely will be dead...by then)...it's why we have to do evetrything we can, right now..with whatever there is (even if it seems futile/not worth bothering for like, 6 months life extension..).
The danger is there (in my case, was atherosclerosis..), the danger is always there...it can come to you. out of the blue,,one day all is going well..the next you are half-dead..in your death bed.
Sudden death syndrome (in young age) is a Very Real thing, dying in your sleep - young...not necessarily that old..many people die in their forties from already 'too damaged/too sick' - too quick, premature end. Life is very fragile and ficker.
Basically...no one can say if we Will defeat aging, but we are trying...and hopefully the results will be better than a few months to 2-3 years of health improvements (like exercise, CR...etc)..
We just don't have the luxury to 'give up'
(on life/on hope;,of life).

Just a 2 cents.

PS: I agree too that AdG's previous predictions were a bit off-the-mark/or quite optimistic/wishful... hopeful,
but not realistic...(enough).
He did say, it would take at least 20-30 years...you can multiply by 2 or 3...and it sounds about right; 50 to 100 years is what it is looking like -- and we have been saying this for Already 10 years - Before; so - time is Piling on More Time/Work...
''work expands...as time goes''.
when that happens, you can't lose hope and abandon ship; you must plow through it and tell yourself - no other choice - i just 'can't' lose hope; if I do and abandon (ship); the ship sinks;
with me, in it. For us, older people (but not too old yet); of course...it's scary to 'run out of time' for so little/weak aging rejuvenation results - we only have about 50-60 years left of life..
that's why it was said that, it may end up, that only 'unborn children' will live to see the day/of defeating aging, and maybe in 50 years; it will not be solved .......(,....still).
I hope not; in the mean time, do everything you can and never lose hope; because minute you lose hope; that's when proverbial and physical grim reaper...inches closer - to the mirage/oasis/you. Only this time, the oasis, is static/fixed (for good) and does not 'recede'.
we just don't have that luxury -- ''we can't'';
abandon = abandon life. (I know this sounds pessimistic...but we Have...to hold on -- for life).
no other choice; the other choice - is not a 'choice' (not one, we wish) - it's the end.

It is also important to remember that achieving LEV, at least initially, does not mean that we will be fully rejuvenated to 20 something's. All it means is that enough of the front-line damage that kills us first will be reduced and/or treated to a sufficient level to buy us perhaps a decade of life while we wait for further improvements. We might not be young yet.

Or to put it another way, we currently add an average of approximately 0.2-0.3 years of life expectancy per year. I'm not saying it is trivial, but I do think it is achievable to accomplish enough to get that up to 1 year of life expectancy added per year, on average in the next 15-30 years. That is LEV. It will probably take longer to bring back youthfulness.

Hi All, thanks for the thoughtful comments.
I agree that progress is exponential, but we cannot know where we are along the curve at the moment: we might think that we have taken off just to realise, twenty years down the line, that in 2022 we were still on the runway. Moore's Law isn't applicable to medicine or, if it is, we haven't seen an accelerated decline in late life mortality yet.
As for where we are now: a huge undertaking such as the complete elimination of cancer (which is nowhere on the horizon) would increase life expectancy by four years at most, so I can't see how a full panel of highly effective senolytics (which is also nowhere on the horizon) could do better than that. The Dasatinib + Quercetin combo that was so successful in lengthening life in mice only marginally improved lung function in humans. If getting rid of all cancer adds four years to average life expectancy, how much would getting rid of pulmonary fibrosis add? Four weeks? The same goes for all the other senolytics, AGE breakers, gene therapies etc. in clinical trials - it's all so piecemeal.
Re: LEV. I have a huge issue with the concept and the way it is interpreted. Most people seem to think that once society "achieves LEV" everybody not at death's door will be alive indefinitely because with every year that goes by they gain another year of life. This is false at the individual level. Someone who is 70 when LEV "arrives" will have a 2% chance of dying before turning 71. Once they turn 71, they will have a 2% chance of dying before turning 72, and so on. It won't be long before they are dead. Having said that, most teenagers may have already reached LEV since they have four decades of likely health before mortality rates start climbing steeply.
Hell, I may make it to immortality myself since I am over four decades away from the age at which half of the women in my country are dead (86). By then, it is entirely possible that life expectancy will be 100, and by the time I reach 100 it will be almost 2080. I can believe that in 60 years time billions of nanobots will be roaming my cells, fixing them at the molecular level.
What I don't believe and I wish biogerontologists stopped saying is that we will have aging under medical control in 15 years. In mice maybe, not in humans given the translational hurdles that we'll have to overcome even if the science is eventually proven right.
In my opinion, pushing this LEV by x date idea, or at least it's distorted interpretation, does nothing but damage anti-aging advocacy.

@Barbara T.: Well said and I agree with everything you said. I like the way you state LEV, the probability of dying stops increasing each year. At first, when LEV is achieved, it remains constant and, one hopes, eventually it will begin falling. I think this is the way I am going to state it for now on.