Forthcoming Book: Replacing Aging
Replacing Aging is a forthcoming book on the treatment of aging as a medical condition. It is presented as putting forward a similar point of view to that found in Ending Aging by Aubrey de Grey and Michael Rae, meaning that the research and medical communities should place a relentless focus on damage and repair of damage. Aging is caused by an accumulation of molecular damage of a few distinct classes in and around cells, that damage spiraling out into a complex network of interacting downstream consequences.
Fully understanding that network, fully understanding the progression of aging, will take the rest of this century, or longer. The root causes of aging, these forms of damage that arise from the normal operation of a youthful metabolism, are much less complex in comparison, and, at this time, are far better understood. Therapies resulting in large benefits, such as significant extension of healthy life and significant reversal of age-related disease, are more likely to arise from work on the causes of aging than from work on understanding the complicated progression of aging. That much is in the process of being demonstrated by senolytics that destroy senescent cells.
Unfortunately, the research community is still largely focused on understanding the intricacies of aging, picking apart the details of the complex, damaged disarray of an aged metabolism, and aiming at no more than a modest slowing of aging. There is comparatively little interest in applying what is already known of the causes of aging. That must change.
Replacing Aging outlines how aging will soon be reversible as a result of the advances that are being made in regenerative medicine. The book explains the enormous complexity of aging and how the accumulation of myriad types of macromolecular damage in the body essentially precludes a pharmacological solution to the problem of aging. Nevertheless drugs remain the primary focus of the anti-aging field. Instead of drugs, a decisive way to erase all forms of age-related macromolecular damage at once would be by replacing old worn-out tissues with new young ones. As the book describes, an ability to replace all body parts seems more and more likely, if not inevitable.
Regenerative medicine is developing increasingly functional lab-grown cells, tissues, and organs that are being transplanted into patients today to treat diseases or repair damage. With continued improvements, cells and organs could be used in a more comprehensive manner to replace all body parts and reset the aging clock to near zero. Even the brain can be progressively replaced at a cellular level over time without a loss of self-identity. Existing examples demonstrate that complex brain functions can if given enough time change their neural substrates. And new brain cells added to old brains can form remarkably normal connection patterns. These findings together suggest protocols for brain rejuvenation. Thus, this book heralds the day in the near future when, if we choose to, we will be able to live much longer healthier lives as a result of replacements made possible by regenerative medicine.
Is Longevity actually just Replacing Aging?
"I was a bit of a weird kid growing up. I realized at a young age, in early elementary school in fact, that we are biological machines and that even if we stay healthy, we will eventually break down with time. I didn't like this and wanted to do something about it, so I knew I wanted to be a molecular biologist working on longevity before I even knew that the words "molecular biology" and "longevity" existed. Then in high school, I started reading on my own everything I could about how we function at a molecular level."
"Macromolecular damage is aging, at least from a biologist's perspective. Any other definition such as motor, immune, cognitive performance, for example can lead to claims of rejuvenation while the actual process of macromolecular and cellular decay proceeds without hinderance. This is an important point in the book because many in the aging field use only indirect markers of aging and are open to misinterpretation and false claims."
Aubrey de Grey's Review of "Replacing Aging"
The key to understanding that aging is not a mystery is to understand that it is not a phenomenon of biology, but of physics: it is fundamentally the same thing in a living organism as it is in a car, or an aeroplane, or any man-made machine. Once one realises that, it is a small step to realising that the approach we take - with dramatic success, when we try - to preserving the function of a car is sure to work just as well on the human body, once we develop the corresponding techniques to a level that matches the greater complexity of living organisms.
The author wastes no time in highlighting this key point - not merely in the abstract, but by getting down to specifics. He notes that the way we keep a car going is by preventative maintenance - damage repair. In other words, by maintaining the overall structure and composition of the car as it was initially. And that, of course, what inspires the title of the book, because preventative maintenance is largely about replacing worn or damaged parts.
The world needs far more books like Replacing Aging. In the past year or so, a few other gerontologists have published general-audience books explaining what this field is about and why it is so promising right now - and they all have different styles and will benefit different audiences to different degrees. In my view, Replacing Aging stands out as a shining example of how to get the public to break free of the fatalistic shackles that are so impeding the crusade to create a post-aging world.
Like Aubrey said, more and more mainstream scientists can say this without the risk of losing their grants and/or position. Curing aging is now almost an acceptable concept in the science world.
Aubrey full review:
https://www.reddit.com/r/longevity/comments/k8fjlf/aubrey_de_greys_bimonthly_editorial_a_review_of/
Hey there! Just a 2 cents.
That is a great thing (by AdG) to spread the knowledge and let people know, especially the skeptics (I included myself in that), because we all have a good dose of skepticisms with anti-aging therapies (we've been deceived before/lots of failed/failures and why the public doesn't believe anything/lost hope and now suspicious of 'get rich quick/get young quick' therapy/nor cares to; like just wanna die..that's it), the large public is hardheaded (a good thing sometimes, not here) about aging; they only want 'healty aging' anti-decripting/anti-bad health....nothing much related to 'aging'...longevity/maximumal specie lifespan. Most people Want to 'age' 'gracefully'...to feel that you mature and 'gain 'with age''...is understandable...with gaining wisdom and knowledge/experience and maturity...with age - but...the thing is...you still age and still 'march on' towards your end (The March towards the Gallows). This book may not change things that much, sadly, because there a zillion books/e-Books on antiaging...and STill people not hooked all that much...the books are put in the 'bargain bin' (trash/snake oil)...when they should be the Most Important thing to their Very life. Just the other day on a UK mail website that shows daily news: 'anti-aging therapy/promising'...and then...go read the comments...and weep
(for humanity). Still, I wish lots of luck on the book selling and helping spread bioeducation to everyone down to the most 'anti - anti-aging' (double negation, thus pro-aging).
Just a 2 cents.
Ps: I fear in the future we may see people go in the streets (like for COVID and anyother manifestation about a social/public ill)...people with PRO-aging signs in the streets walking and manifesting that aging is natural and genetic is against god/immoral...while another crowd of younger people carrying ANTI-aging signs, heck even carrying AdG's Replacing aging book....
while the PRO crowd 'burn' that book (book burning was something in old times; now it's
eBook Deleting instead of burning physical 'in paper' books). I hope we don'T a civil war...I mean COVID/BLM/child abortion (pro-life/con-life)/homosexuality... and other controversial/polarizing issues...are pretty close; and so will aging be too. Sounds about right about the future (may look bleak), the vaccine is a welcome answer to COVID (as long as is safe; since it is cas9-Crisp ediiting of the virus proteins)). The more welcome answer would be a therapy that reverses aging altogher.
PPS:
If his book does not talk about nuclear DNA, telomeres or epigenetic or mitochondrial ROS, it's lacking a Huge part; he must answer to that and show how to repair the genome/telomeres and maintain their length; the only two things from SENS that could make LEV are if they DNA repair, that Lipofuscin removal, and mitochondrial 13 proteins expression genes in nucleuse...but besides that I don't see what/how they will repair the DNA damage (removing glucosepane/AGEs...is not enough). How will he overcome the Leonard Hayflick final barrier to all cells. If he is able to create new cells with lengthened telomeres, a sdrastically reduced telomeric DNA shortening rate, repaired DNA, residues removed, chromosome unloosened, removed lipofuscin/progerin...as like iPSCs epireprogramming; then I will believe him (about LEV) but until then hold your breath. If there is not telomere lengthenning or stalling...then LEV wil never happen unless some 'hack'/circumventing this mechanism and replicative Hayflick limit of cells. Still, the book gives hope that is what is truly needed and 'explanations' in layman terms for most people; so that they can start believing/changing their point of view about (their own) aging/age; maybe then more Funds will come to SENS and other therapies (doubtful). We just need more investors to believe in his book and then the will 'venture capital' invest in it (a good thing...instead of being rich..and/but dead. If I had a billion to spare I'd surely put a large chunk on the most promising antiaging development; it would never be a waste/throwing money out the window...because..the other thing, is dying anyway; rich or not; so they saying is spit the cash, and spend it (like no tomorrow when you are gone forever)). Merry Chritmas and Happy New Year in advance.
PPPS:
''Regenerative medicine is developing increasingly functional lab-grown cells, tissues, and organs that are being transplanted into patients today to treat diseases or repair damage. With continued improvements, cells and organs could be used in a more comprehensive manner to replace all body parts and reset the aging clock to near zero.''
That could circumvent the problems of aging/cell hayflick...but that remains to be seen; if we can Replace Total Body/Organs/Cells...made 'in lab'...with new ones; this is akin to 'stem cell' replacement of cells...but with an infinite supply of 'lab made' stem cell ones...this could circumvent almost all problems; but we don't know the feasability/how it will work in a real body - just look at patients receiving organ transplants or 'dolly the sheep' clone(d)...it does not always go as planned with new 'cell/organ' replacement/retransplant. It is the 'car repair/parts replaced' analogy; certain organs were transplanted in humans..but they never last because are 'foreign' and the body can 'reject them'...so I guess there are still lots of challenges to the 'replace entire body with new lab-made one'.
The positive is that recent trials with 'stem cell' transplant in patients...saved them; so it does work. We will have to make it work for All Cell/all organs/entire body (that's no small feat); Let's hope.
Can somebody tell me when we will be able to reverse heart failure, or a bandaid approach to keep someone alive until theses regenerative therapies are available. Will overseas offer them first?
@Reason, have you read this book? Which do you recommend? This one, David Sinclair's or both? Thanks
Hi august! Just a 2 cents.
I don't know when and heart failure is a multi-cause thing; thus, it requires a multi-intervention.
Heart failure can be caused by atherosclerosis, infection, enlarged heart or reduced heart chambers/thickening of the wall, valve dysfunction, electrical problems (arrhythmias), hypertension (systolic/diastolic), edemas, fibrosis, reduced NO (nitric oxide)/reduced vasodilation, excess TNF-a/TGF-beta/Angiotensin...low grade heart inflammation/oxidative stress to cardiomyocytes, excess exercise (exhaustion), traumatic stress, diabetes, obesity, sarcopenia/frailty/meager (the extreme inverse of morbidly obese) smoking, excess alcohol, family (genetic predisposition) history/parents died of it/siblings too and the list goes on.
Thus, right now, there is not that much to be done; heart transplant, reducing sodium intake, exercising, diet change (remove junk, turn to veggies or mediterranean/keto diets), stop smoking, lose weight especially obese/over BMI (if frail/meager - Don't - lose too much weight...gain some normal weight/muscle for your size (check BMI); if you are too weak/too anemic/too frail/no energy...your heart can stop; it too will be too weak to pump anymore); gaining some muscle reduces sarcopenia (muscle loss/wastage/muscle fiber thinning); same thing with your heart...it needs 'some' light exercise..it is a muscle too (made of muscle fibers to pump). If you can't do any exercise right now, then don't - know your body/listen to your health/pain/symptoms your body is communicating to you; until you are better and can very slowly do some light exercise.
Apparently, there are about 5 levels of heart failure; first 3 or 4 levels are sort of manageable...but on the 5th last level; it is nearly irreversible and heart failure will happen, despite doing the invertion, thus it is at 'paliative cares'/terminal phase. The heart is just too weak/damaged; thus, the only saving is transplant of heart/mechanical heart/pump...and that is a shot in the dark 'and (a shot) in your heart' (but better than nothing, because without your heart anymore; it is the dark, forever). I also saw beta-blockers and angiotensin converting enzyme inhibitors help.
Reversing heart failure requires a life commitment and 50% die of heart failure in 2 years after heart symptoms appearing before (1 out of 2 is affected of heart disease failure; in US it's probably skyrocket even more; thus, that means at least some 100s million people in US are affected with heart failure and may pass away of it if it progresses to the late stages). Overseas no different, heart failure problem is substantial in Europe too; only in certain mediterranean, south-american, asian and african places that heart problems are low (because of their life style, genetic, no pollution, exercise daily and natural diet), in effect they hit the jackpot by their life choices which makes heart problems (as %) much lower in these populations. To me, studying a heart that beats for 500 years (in a clam), is what matters to overcome the aging heart; and everything points to making sure we preserve those telomeres in our cardiac cells (which are key elements to the heart function), a heart ages and has (supposedly) a 'finite' number of heart beats...60 beats x 1 minute (per min) x 60 min x 24 hours x 365 days x 100 years = 3,153,600,000 beats avg. in a 100 year lifespan. If we age at the same speed, with no intervention, than it is about 3 billion heart beats in our life that our heart can take before collapsing. But that is if we don't do anything and the heart 'progresses/ages' normally to the end - until 100 years old. If we do intervene, than we might possibly be able to stop the cardiac cells from dying, replacing them or keeping them functioning so that we could keep our heart beating much longer (like that heart beating 500some years); now that heart beats slower...like 1-10 beats per minute (these animals are metabolically nearly dead/slow mo metabolism and that is why they live this long), so it kind of shows the 'maximum beating potential' of a heart...
mouse: 700-1000bpm - 2-4 years
human: 60bpm - 100-120 years
clam: 5bpm - 400-500 years
As we can see the heart beating capacity is 'proportional' to the length of lifespan; a clam beats 10 times slower...it can lives roughly 5+ times longer than human, and 100times longer than mouse; because they beat much faster; so a mouse heart, human heart and clam heart show that all their heart beat 3-4 billion times - same limit...and that seems the roughly maximum capability of a animal heart to beat..but if you beat slower (as in 'spend it slower/burn it slower') then you can reach like a clam 500 years...or spend it Really fast (at near 1000bpm)..like a mouse and die in 2 years. For humans, it is not possible to have such low heart rate (bradycardia), in fact bradycardia is a common thing of larger hearts and hypotension; which can be deadly for humans. So we are left with...then how can we overcome this 'beating limit' on a heart...well, humming-birds and certain animals have extremely fast heart rate...and still live quite long (albeit they do 'night torpors' to compensate for daily heart-taxing flights; by slowing down their metabolism during sleep or hibernation/torpor)..but, maybe it is possible to overcome this rough organ limit and preserve pumping function; so that our heart is not an 'old heart' but a young heart once again...irrespectively of How Many beats it has beaten so far...because when I look at the clam's heart...it can beat this long but it is its 'normal aging' process (which is slowed down), maybe a rejuvenated heart could (theoretically) pump indefinitely so long as it would revert in entirety its tissues by tissue replacement. When you think about it the heart is one of the least complex organs, it's basically a sack (with connected pipes/valves) that pumps blood/a muscle that 'flexes' contracts/dilates in and out/on and on like a pump; compare that to the complexity of a brain...it's two different things. It's why a mechanical/electronic robotic heart could save us (transplant of real heart or a electronic one), all we need is 'pumping the blood in all veins/organs'...the heart's main function. Now, if we want to preserve our heart organ, than we have to stop cardiac muscle cells/myocells and endothelial cells of dying of aging.
Just a 2 cents.
@CANanonymity
I find your posts to sometimes be interesting, but they are WAY TOO LONG for comments on a blog. More people will read your ideas if they are presented in a clearer and more concise manner.
Also, as others have said before, saying "Just a 2 cents" every time you post is both not necessary and rather grating for some reason.
Again, I think your posts often contain interesting ideas-I am not trying to discourage you from posting!-but it would really help everyone else reading them if you try to improve your presentation.
@gheme:
Seriously dude, as long as he isn't offensive CANanonymity can write whatever the hell he wants, in however many words he prefers.
You have the choice to not read his posts if you think they are "grating."
Personally I find CANanonymity's penchant for saying "just 2 cents" quite endearing, and since this isn't a writer's workshop it really isn't anyone's job to tell commenters that they should improve their presentation.
@Barbara T.
You're right. Sorry if what I said came out as overly negative. It's just that I think CANanonymity often makes good points that are worth thinking/talking about, but that it would be a lot easier to think/talk about them if they were presented in a clearer way. After all, this is primarily a blog for the popularization and discussion of scientific ideas which is read by plenty of lay people, and not an academic journal or similar.
The average lifespan two thousand years ago was 18 years, a thousand years ago 35 years, and in 1900 very few lived over fifty years. Evolution has not had the chance to work on longevity so genetic modification using gene-editing tools like CRISPR should be our priority. Removal of senescent cells and genetically modifying mitochondria to produce NAD+ should also be a priority. I intend to start taking 200mg of Dasatinib and 2000mg of Quercetin every eight weeks probably for three days whilst eating foods high in Quercetin to see what effect it has on me. Replacing body parts should be a last resort.
@gheme
No problem. The way I see it, CANanonymity is quirky but variety is the spice of life. It is also nice to see someone's emotions shine through at times, and he does have some interesting takes on things.
I hope he continues posting... he is not everyone's cup of tea, but then neither am I.
We do need to understand why some species like the clam and Greenland shark live so long, https://youtu.be/Djj3-jF19F8 I think we will see the healthcare business move more towards prevention, partly to save money so more genetic sequencing and internal monitors which will be good for aging research.
Reason again hits the nail on the head. Just lead on.
But again ( I had this dispute with reviewer before ): "Preventative medicine" is much more than just "replacing worn or damaged parts": the latter may lead into a "dead end", delaying success, what everybody just wants to avoid