95% of Centenarians are Frail
Survival to 100 years of age is a rarity at the present time, but if the present slow upward trend in life expectancy continues, most people born today will live to 100 or more. That trend will, of course, not continue as-is. The past trend was due to incidental effects of public health measures and general progress in medicine on the mechanisms of aging. The trend in life expectancy will leap upwards with the advent of rejuvenation therapies that deliberately target the reversal and repair of those mechanisms. But that is a topic for another post.
Here, let us focus on what actually happens at the present time to people in the last stages of aging. I think it is important to look at the reality of the situation, as in some circles, centenarians are held up as exemplars of health in later life, and the goal of medicine put forward as upholding the slow trend of increased life expectancy, thereby enabling more people to follow the same path. This is a terrible goal. Centenarian health is not good. As today's open access paper shows, near all centenarians are frail. Frailty is a life-limiting set of circumstances, caused by a high burden of the cell and tissue damage that lies at the root of aging. Frailty manifests as physical weakness, dependency, vulnerability to infection, cognitive decline, and a high mortality rate. No-one would choose to be frail, given the option. Mere survival should not be held up as an exemplar of health.
The goal of developing rejuvenation therapies is maintenance of health, the elimination of suffering and limitations such as frailty, cancer, cardiovascular disease, and so forth. Increased healthy life span, ultimately far beyond present human capabilities, will be a happy side-effect of keeping the human machine in good running condition. Rejuvenation is just another name for preventative maintenance sufficient for good operation: identify the damage that limits capabilities, and remove it before it causes major breakage. That is a lot more complicated in a mammal than it is in a car, but the concept is the same, and it will work just as well. If the entire field of longevity science turns into low-expectation-value efforts to modestly slow aging with the goal of making more frail centenarians, then we will have missed the point of the exercise, and missed the opportunity to achieve a great advance in the quality of life for all of humanity.
Based on the Chinese Longitudinal Healthy Longevity Study (CLHLS, 2008-2018), individuals aged ≥ 65 years having complete data of frailty were recruited. The present study reported the prevalence of pre-frailty and frailty among the population with a mean age of 85 years, which were 54.1 and 26.3%, respectively. Females were predominant among frail population in all age groups whereas males were dominant among pre-frail individuals aged ≥ 80 years. Both pre-frailty and frailty were strongly associated with multiple adverse outcomes. Males and the young-old (younger than 80 years) were the most susceptible to the risk of mortality.
Healthy aging is an important goal of the public health in the 21st century. However, a huge gap exists between longer life and healthy aging. The present study indicated the high prevalence of pre-frailty and frailty among the Chinese longevous population, which is consistent with the results from 1,253 centenarians in the 5-COOP study countries (Japan, France, Switzerland, Sweden, and Denmark). It demonstrated that the heavy burden of frailty among the longevous population was globally substantial. Notably, only 5% of centenarians and 11.1% of nonagenarians were non-frailty in the present study. Similar results were observed among centenarians in the 5-COOP countries.
Additionally, the present results comprehensively demonstrated the association between pre-frailty, frailty, and the risk of multiple adverse outcomes. It implies not only the high consumption of healthcare resources of the frail elderly, but also the suffering of patients themselves. Hence, the epidemic of frailty could be considered as one of the great barriers of healthy aging.
What is surprising is that there are 5% that are not frail.
P.s. I liked the term "young old"
Isn't Betty White around 100 years old, she would be Characterized as not frail.
arstechnica.com/tech-policy/2018/04/curing-disease-not-a-sustainable-business-model-goldman-sachs-analysts-say
they should do a aging study on TENS unit. would think it could increase life with 10 years. increase in movment, hormones, stem cells, bone growth. ad vitamins to that and it will create synergy. imagine growing old with red light therapy and TENS unit, wow. cycle it with rapamycin and senolytics
Hi there! Just a 2 cents. TL DR: 2022 is about to get worse before its gets better; get dire.
And get in dire -straits.
There are two things that can reverse aging (the rest, doubftul, perhaps stem cell replacement, doubt it, did not work in mice), and that is: Epigenomic Reversal and DNA Damage Repair.
Both, now, are limited; but the latter, seems even more limited. DNA Damage Repair, we know, causes accelerated aging (ICE mice that age 50% faster by having lesion mutation - Double-Strand Breaks appearing in their cells - on purpose; and they age nearly double faster than regular wild-type mice; thus, they said that DNA Damage Repair Inhibition = Accelerated Aging, or Progeria (such as WRNS (Werner Syndrom))/HGPS progeria 'fast aging' syndrome..these fast aging syndromes have Inhibited DNA Damage Repair (WRN helicase is dynsfunctional in WRN people); how so? For example, the main DSB repair pathways are EXO1 and WRN helicase, ATM, and they activated by SIR6 (Sirtuins 6), we know that SIRs are Histone sirtuins which are DNA Damage Repair 'Activating/Promoting' elements; in essence, SIRs Activate DNA Damage Repair Pathways, and that is why SIRs were more Elevated in Long-Lived Rodents (for example Naked Mole Rats or Beavers have much higher SIRs activity than mouse; they live multiple folds longer than a mouse (3 years vs 30 years). The study said that the SIR activity was weak(er) in mouse = DNA Damage Repair Weak/Inefficient = Accelerated Aging = Short Life (in mouse).
Now, it,s the link between DNA Damage Repair and Epigenetic Aging; Double-Strand Breaks (DSBs) (are the Consequential DNA Damage) which cause Epigenetic Drifting..and thus, that epiclock would advance = Aged Epiclock = Biologically Older = Closer to Natural Biological Death (of aging).
It's important to Stress Consequential; because in the rodents of various greatly-diverging maximal longevities,
number of DSBs correlated to Maximum Lifespan Potential (MLSP).
DSBs - Need - Repairing, that is the DNA Damage Repair, which the DSBs are Specifically Repaired by the EXO1, XCC, ATM, TP53, helicases, BER and NER pathways. Base Excision Repair (BER) and Nucleotide Excision Repair (NER)...
''Furthermore, previous attempts to increase DSB repair efficiency by overexpressing DSB repair enzymes gave disappointing results, as they often resulted in decreased repair and cellular toxicity. We previously found that overexpression of SIRT6 was the only approach capable of increasing both DSB repair pathways without causing negative effects (Mao et al., 2011).''
It seems that DSB repair efficiency increasing has reached a limit - which is not very much; in essence, we can't seem to Improve DSB repair - more than that....and we know that DSB repair therapies don't make mouse (3 years) live long like a naked mole rat (35 years). They oftenly increase lifespan by 20-30%, maybe push'in it - 50%...that's the summum so far - for DNA Damage Repair therapy. Of course, it'S better Than Nothing...we'll take 50% if it means 50 extra years of lifespan to live to 150 years...but I doubt it.. let us remember that rodent and insect lonfevity studies are Always Stronger in effect..and much weaker in humans/primates...larger/already longed lived animals;;as such we would need to tempt our optimism and say we might get half that or a third or a quarter or less of those mouse/house fly/ C. elegans worm results. The boost stands..but it becomes weaker...the longer Already the animal is (that'S the 'already optimized longevity' of humans...not getting anymore/redundant).
With that asaid, there are HGPS humans that live 15 years old...and there are Jeanne Calment humans that live 122 years (well at least - 1 - Her)....like a mega difference in longevity (she almost lived 10 times longer ...like 10 Lives - in 1; 15 vs 150 years old, that is the Future for humans, reaching 150 instead of dying at 15 of HGPS). But that's not enough, AgG, a 1000 years old is born...we need to aim 1500, one more digit. Now we're talking rejuvenation( True).
OUtlandish? Baloney? 1500...how about 15,000 years like 3 lives of a 5000-year old Tree each
1 live (BristleCone Pine). I like the sound of 6 Digitis Lifespan. No more 2-Digits, 2-bit lifespan...
3-Digits, is bare minimum = 100 years, (1 life of a hundred ) at very least; but Several of (these 1 life) them.
Bored Out (living 1000 years decripiting in pain - fun?) Selfish? Stop pretending to be *mmortal we all die?....etc...
I will carry on believing we will reach the Several 3-digits lifespan, the Bi-3 digits ('100' x 2 = 200 years...), we have to live double centenarian lifespan to call this rejuvenation (150 is just pushing it but still not True Rejuvenation, as in Way Above Maximum Lifespan; it's just 30 years extra over human maximum). Bi-centenarian...just like bicentenarian trees...that will be the real first step/True rejuvenation.
We might able to Reach the Big 4-Digits, but doub it (1000 years it still a sort of pipe dream but we closing'in on it, if we get 150 yaers to find it, we stand a chance, by getting 150 of time to make that happen; otherwise it will not happen in our lifetime..only the future Unborn children in far future...next or second or third century from now).
The more I read about biogerontology the more I realize the limits we hit/'walls'....like, we may do rejuvenation - certainly- but The Result of it..will be weak(er) much weaker than hoped (I mean..it's a Miracle we even reverse aging - not complaining, it's extremely Admirable..it's just that we Still Die), 'settling for living an extra 20 years - that's about as good as it will Ever get in your life'...That's the real problem. Our inability to solve it/finish it and make it happen, we partly solve it and we obtain Partial Results, these partial results are Very Partial...not a little partial, Very Much/A Lot partial..I.e. -Very Limited- and is why the results are weak each and every time, in every frickin study. I remember reading a study about C.elegans that live 250 Days after a mutation, they were slow growers and metabolistically dead...they live nearly a Whole Year...vs Regular C.elegans that live 20 days....it was a breakthrough, liveing 10-times Longer....like HGPS people (15 years) vs longevous people (120 years). About 10 times...we have seen almost Nothing give 10-times lifespan extension in all therapies so far. It's always crumbs/pittances % of extension... I hope we solve this problem because in the future 'lack of result/Strong result'...will mean our (regular timely) demise ('on (the dot) clock').
Imagine living 10-Lives of a Centenarian...1000 years; we must Reduce the Rate of Their Ageing - by 10. We can't (really so far) Improve DNA damage Repair all that much - hit a wall..so now what?
Just a 2 cents.
https://www.sciencedirect.com/science/article/pii/S0092867419303447
https://www.biorxiv.org/content/10.1101/808659v1.full
PS: Epigenetic aging is the other one...and we see that DNA methyltransferase are Called on DSBs to 'Induce Repair'...and we know that DSBs engender Epigenetic Clock landscape change/advancement; it would because DSBs = MLSP; but even more so
DSBs = Epiclock = MLSP.
You can move the needle on the clock or the DSBs by repairing them.
The former is now very hard if impossible to improve all that much (let'S hope)...so it leaves the latter...epiclock tinkering...epireprogramming is Severly Limited right now;
The Limits:
- It will cause teratoma formation after 10 days Octs Sox Nanog concoction of 'pluripotent stem-cell markers' that 'open the 'gates of the epigenome' -> Havoc.
- Full Reprogramming = loss of cell identity 'erasing an school chalkboard - clean slate - no more idenity/memory'; it is fatal in mice; the full reprogramming simply does not work because the cells lost their identities and are now like germ cells (stem cells) 'pluripotent/totipotent' and 'Dedifferentiated state' (they lose their Differentiated 'adult/Mature' identity state' -> like going back to puberty and Before that, like a child). It does 'function' in an adult mouse..it'S deadly.
- Thus, Only, Partial Reprogramming is Possible, because it does not Reverse Totally the Epigenomic Landscape (Peaks and Hills; are Inversed in Full Reprogrammation; while Partial Reprogramming only stops it 'at the middle' but not Total Inversion of cell identity; kind of like the yin-yan sign.. partial reprogramming does not make black be white and white be black..it strikes at Grey Mid neutral); thus, the cell keeps its identity but its Epigenetic Clock is Reduced..in human fibroblast cells..improvement in epireprogramming = 30 years* reversal of the epiclock -; that's probablt the *Very Best...of All the studies seen far in terms of True Rejuvenation. If excluding the Best = CR/Calorie Restriction (even it is not sure to give 30 years extension in humans), we know CR activates SIR6/Sirtuins = Improve DSBs DNA damage repair; SIR6 activity = MLSP. Everyone would take a 30 years body/biological rejunveation by epirepromming; so far, DNA Damage Repair therapy Is Not capaple of doing that (in humans..perhaps in mouse..but humans not very much)...and CR possibly neither (it might give an extra 15-20 years of healthspan and a little bit of maximum too increase but less than 5 or so). At least the good new is we improved the efficiency of it..but it carries an Immense Risk...taking a Epigenetic Therapy - is Being A Guinea Pig/Russian Roulette..like taking a covid mRNA vaccine..risks can happen - side effects; and you may die in a few days of it (of the therapy's side effects); or develop crippling disease - from the therapy. That'S the scary part (and where FDA will go against, understandably). Plus..other limits, epigenetic reversal is Temporary ( that made me SAD....really sad), it is only 'per day'..or like...if you take a epireprogramming after day 9 reprogrammation..on day 12 the effects wane..and resurgence of senescence...4 - DAYS after only. That means like taking vitamins - Epigenetic Reprogramming will have to BE PERMANENT - DAILY..not some thing you do per 5 months or per year..it would need to be done All the Time and at All Times..to keep your body the same..because the body Reverses the Reprogramming Only Days after...that's extremely sad. I thought it lasted Once it was done..nope it lasts nothing...we have to improve the Durability and Longevity 'half-time' of the Result, so that the results Last Long...not barely a day long?...it'S almost pointless..we would need a rejuvenation Daily..that is the Future - plugged on the machine (always) to outcome death. Become Cyborgs in essence.
@CANanonymity:
"An analysis of the history of technology shows that technological change is exponential, contrary to the common-sense "intuitive linear" view. So we won't experience 100 years of progress in the 21st century - it will be more like 20,000 years of progress (at today's rate). The "returns," such as chip speed and cost-effectiveness, also increase exponentially. There's even exponential growth in the rate of exponential growth. Within a few decades, machine intelligence will surpass human intelligence, leading to The Singularity - technological change so rapid and profound it represents a rupture in the fabric of human history. The implications include the merger of biological and nonbiological intelligence, immortal software-based humans, and ultra-high levels of intelligence that expand outward in the universe at the speed of light."
The Law of Accelerating Returns
March 7, 2001 by Ray Kurzweil
95% of Centenarians are Frail...
Same can be said about generation Z(ombie). Frail bodies and minds.
Frailty is not exclusively a function of age.
https://en.wikipedia.org/wiki/Generation_Z
'Globally, there is evidence that the average age of pubertal onset among girls has decreased considerably compared to the 20th century, with implications for their welfare and their future.In addition, adolescents and young adults in Generation Z have higher rates of allergies higher awareness and diagnoses of mental health problems, and are more likely to be sleep-deprived.In many countries, Gen Z youth is more likely to have diagnosed intellectual disabilities and psychiatric disorders than older generations.'
Wouldn't arginine and carnitine reduce some aspects of frailty. At least muscle loss.
It seems unlikely to me that early rejuvenation treatments will reverse frailty, only that they will postpone frailty amongst the prefrail 60+ population
also, using EDTA iv to remove the vaccin damage in young age will be a must to grow old. its shown to ad 15 years of lifespan when a 30x cycle is complete. no risk of alzhimers or chronic pain. wich will make all the other supplements work better
@JohnD
It depends on the approach taken and what really works. However, I would say that if you can postpone if for 10 years you could quite probably reduce it a bit
Those who are FRAIL will eventually FAIL. Slow aging may extend life to a 100 or more years, but the quality of life will be very low - a life of constant torment and suffering and inevitable death. Their DESTINY is their DEATHtiny.
Rejuvenation is absolutely necessary to make life worth living.
My MOTTO is : to be USEFUL i have to be YOUTHFUL. ( that is to be useful to myself and others)
@Ray Kurtzweil: " the law of accelerating returns" may not apply to medical science and technology because of government regulations which slow down development of anti-aging cures and insufficient funding in anti-aging research - curing aging is a low priority for most governments, corporations, wealthy individuals.
It would seem that Centenarians might have reduces frailty in their eighth and ninth decade compared to others.
"Additionally, there was a trend toward lower incidence of fracture among the oldest individuals, as compared to the general very old population in the United States."
See the article Lower Fracture Incidence in a Population of Nonagenarians
https://www.fightaging.org/#:~:text=Lower%20Fracture%20Incidence%20in%20a%20Population%20of%20
I think we need to balance this against the constant pressure from TPTB to LOWER life expectancy. It started with the Flexner report in 1910, continued with general use of fluoride in urban populations, soy in human diets in the 1950's, various pesticides/herbicides and plastics in the 1960's, obesity and GMOs in the 1980's and 1990's, 4 and 5G EMF and their pièce de la résistance COVID-19 and "vaccines" currently.
High net worth people can and are evacuating this deadly environment to give themselves a fighting chance. The rest of us have a hell of a fight against all this while pursuing longevity.
re: Alex and 20,000 years of progress. Larry Niven wrote a series of SciFi books called "The Known Space Books" ("Ring World", "Ring World Engineers", "Protector", etc.) with a species of beings called "Puppeteers" that's highest priority was safety due to their unlimited longevity otherwise. If you look at the causes of death on the Morbidity and Mortality tables, I think 20K years is very improbable even with infinite longevity.