Yes, in Principle Aging can be Controlled and Altered to a Large Degree
The popular science article I'll point out here is written from a programmed aging point of view, in which - to simplify greatly - epigenetic change is considered to be the root cause of aging, changing the operation of cellular metabolism so as to generate damage, dysfunction, and death. One of the authors maintains a blog, and you'll find much more on his take on programmed aging there. I consider the opposite view to be more plausible, that the root cause of aging is accumulated damage, produced as a side-effect of the normal operation of metabolism, and that where we observe epigenetic changes in aging, they are a response to rising levels of damage. Placing this crucial difference to one side for one moment, the article below does makes an entirely valid point, which is that the enormous evolved variation in life histories in the natural world - in the pace and character of aging and species longevity - indicates that it is in principle possible to engineer a radically different human metabolism in order to create individuals who undergo slower aging, and down the line that sort of approach could be used to produce negligibly senescent or even ageless branches of humanity.
Humans age gradually, but some animals do all their aging in a rush at the end of life, while others don't age at all, and a few can even age backward. The variety of aging patterns in nature should be a caution sign to anyone inclined to generalize - particularly the generalization that aging is inevitable. Life spans range from Methuselans great and small to genetic kamikazes that die of a spring afternoon. Submerged dragonflies live four months, adult mayflies half an hour. We live some 70-odd years; but the meristem of the ginkgo may be millions of years old. This range becomes all the more impressive when we realize that the genetic basis for aging is widely shared across different species, from yeast cells on up to whales. Somehow, the same genetic machinery, inherited from our common ancestors at the dawn of life on Earth, has been molded to generate life spans ranging from hours (yeast cells) to thousands of years (sequoia trees and quaking aspen).
And it is not only the length of life but the pattern of deterioration within that time that varies widely. Aging can occur at a steady pace through the course of an entire lifetime (most lizards and birds), or there can be no aging at all for decades at a time, followed by sudden death (cicadas and century plants). Our own "inner assassin" works with stealth, like an evil empress gradually poisoning her husband; but other species have inner killers that do their deed far more quickly, and still others appear to have no genetic death programs at all. Such variety is a sure signal for a feature molded by active natural selection, not an immutable law of entropy. The great variety of aging styles among plants and animals suggests it can be controlled.
Suppose we were to remove length of life completely from consideration and compare different species based on the shape rather than the duration of their life histories. However long or short the life span, we display it in the same size box for comparison. Rather than asking how long they live, ask instead whether their populations tend to die out gradually, or if many die in infancy and fewer later on, or if all the deaths bunch up at the end of the life cycle. The strange bedfellows that appear as neighbors on the chart are utterly unexpected. For example, at the top of the chart, with low mortality that rises suddenly at the end of life, humans are joined by lab worms and tropical fish (guppies)! In fact, in terms of aging profiles, we humans look more like the lab worm than the chimpanzee.
Styles of aging in nature are just about as diverse as they can be, which suggests that nature is able to turn aging on and off at will. With this in mind, we may be forgiven for regarding theories that explain why aging must exist with extreme skepticism. Whatever our theory of aging turns out to be, it had better make room for plasticity, diversity, and exceptions.
I do not believe that building a variant of human biochemistry to produce negligibly senescent individuals is a near term project in any way, shape, or form. It is certainly possible, and may well be accomplished, but in the same sense as building out human habitats in high Jupiter orbit is possible, and may well be accomplished. Both are projects that could be eclipsed and rendered retro-futures by any number of advances over the decades ahead: why invest in building a negligibly senescent human biochemistry in a world in which we can discard our biology to merge with the machinery of a mature molecular nanotechnology industry, becoming ageless, durable, and repairable, for example? Or why do it if by the time it is plausible the medical community can already comprehensively repair the biological damage that causes aging?
At the present time we stand at least decades from even a comprehensive map of healthy, normal metabolism. Applications of that knowledge will require longer to arrive, and based on existing experience that work will be painfully challenging. Over the past fifteen years, it has required scores of researchers and a few billion dollars to somewhat improve the state of knowledge for one small set of genes and processes involved in calorie restriction, a very well-studied altered state of metabolism that modestly increases health and longevity. The research community is nowhere near a full accounting of how calorie restriction works, or any way to turn it on safely all the time, or even good ways to recreate some of its effects using the standard panoply of drugs and gene therapies. All of that effort could be repeated ten times over between now and 2030 and researchers would still be only a little further along in the process of figuring out how it all works in detail. The molecular biology of life is fantastically complex.
I point this out, as usual, to illustrate why the SENS approach of repairing damage is really the only viable way forward to radical life extension in our lifetimes. The cell and tissue damage that causes aging - that is the signature difference between old and young tissues - is well cataloged, agreed upon in many diverse fields of medical research, and there are plausible ways to repair it either under development or that are planned out in some detail. Given the vast costs and length of time needed to get to the point of being able to defeat aging by creating a new human metabolism, it is vitally important that we have an alternative approach to rejuvenation and agelessness that requires little to none of that effort in order to progress. It really is as simple as periodically fixing the damage and observing the results, a process that is taking place for senescent cell clearance in mice right now, today. This and other similar efforts in the years ahead will help map cause and effect and relative contributions to specific age-related diseases, but much more importantly will also produce the basis for rejuvenation therapies - and produce them soon enough to matter to people alive today.
Even if you share the damage accumulation point of view, the epigenetic damage has to be repaired, right?
Let's start with CRISPR/Cas9 epigentic editing and see what happens. The causes of aging are interconnected. An epigenetic reset will affect a lot of other components of the aging process in a favorable way.
@Prometheus: Hard to say at this point. It seems fairly evident that things like detrimental cardiovascular remodeling won't go away on their own even if you fix the loss of blood vessel elasticity that is the root causes of the hypertension that in turn causes that remodeling. So it doesn't seem unreasonable to think that some epigenetic alterations are not going to go away readily if you fix the root cause of that change. We will have to see how things pan out when the damage is being fixed.
Hi ! Intriguing!
I'm of the opinion it's roughly 50/50. It's not one or the other, it's both. They compliment each other like 2 systems working in paralel/tandem that create the unfolding 'aging' process.
Stresses of imperfection and flawed reality of our DNA activate or deactivate deleterious genes, that create inflammation and, as such, damage DNA. The damage is 'responded to/acted on' by activation of 'survival genes' and inflammation genes too, in an epigenetic way and 'compensation' feedback response to advancing program. Thus, in a sense, it is kind of 'programmed' and follows a predetermined pathway...but it's not final and we can't do anything about it. The damage seems like the end result rather than the starter; the program started and the damage accumulated - but the damage is still very important to that program; it's like its core element to execute the '(death/aging) program/plan' to a finish.
Gene tinkering is hopeless, its like trying to untangle a gene labyrinth with trillions of tiny-acting genes who make a 'total effect' on aging; it's unsurmountably complex and as such nearly unsolvable (only certain 'master switch' genes can we act on, line in CR that acts on thousands of genes but certain big ones are 'upstream' of the 'downstream' genes, the upstream ones we can try to modulate (Insulin receptors IGF, mTOR, SIR-1, pERK, PIP3, DAF16, p53...); they control millions of genes by themselves), and truthfully, we already tried and we were not capable of anything more than genetic-mimicry of CR.
Damage thinkering is possible.
It's a very fine line that is blurred and you can see it both ways.
'' things like detrimental cardiovascular remodeling won't go away on their own even if you fix the loss of blood vessel elasticity that is the root causes of the hypertension that in turn causes that remodeling''
Cardiovascular remodelling shows fibrosis, oxidative stress, ventricular hypertrophy and elevation of various markers of damage. Hypertension is directly linked to excess stress. Again, this points to stresses, both oxidative and non-oxidative ones, being the major reason we age, as they damage us, changed the epigenetic course towards inflammation spiral resolution/response/activation catch-up lose-game, and thus, premature accumulation of damage and waste.
By reinstoring the correct low-to-stress-free environment, cardiac remodelling is halted. Why I have some doubts that damage removal may slightly fail is because certain studies showed that there was no 'structural damage' and yet, you could see activation of certain deleterious pathways that could activate apoptosis or senescence; meaning 'errors' happen and they can 'create that damage' or those deleterious genes activation. The trick is to make sure the cell makes the least amount of these errors, as they are part of the reality of it.
That means it must be stress-free. Or let's say, not stress-free, but stress-proof or as they 'stress resistance'. When the cell is stress resistant, it functions much longer and escapes most of these errors. Réplicative stress, Oxidative stress (the largest and most major contributor), Reductive stress, Hormones stress (the endocrine/neural system/brain neurons and nerves CNS that activate signals that affect sexual resources and developmental growth (IGF/DAF/SIR/mTOR)) and speed of metabolism (affecting aging).
In mammals, redox antioxidant and nucleotides NADPH/NADH and GSH:GSSG ratios are crucial to maintain that damage low by mitochondrial ROS rusting mechanism after O2 oxidation/respiration and that epigenetic program turned 'off' (aging is all about that epigenetic program 'happening' and 'mutating', Young people show more 'gene silence' than 'gene activation' and mutations accumulation like in old people).
As it was said, only 'all types of damages' reduction can increase maximum lifespan, just like in Calorie Restriction. I think with sENS we will reach that, it's just 'how strong' the effect will be, it may end up - like Calorie Restriction and that LEV can'T be reached because ther 'power' of damage tinkering is not that strong enough to make humans go very far beyond their mlsp. This would even increase the power of the 'epigenetic program' determining lifespan, with damage too. It will really depend on the 'combination' of all these therapies together and see how strong it is.
Still, if it can't alter redox or let's say it can'T alter the 'normal course' of redox, than it will not increase MLSP by much in humans (their natural limit of 122 years old), we will rather see a compression of morbidity and a slight extension of maximum lifespan : humans could live to 110 years old...and die there with SENS. And for Lucky ones, they could slightly surpass MLSP and reach 150 years old, not much more though; certainly not reach a 1000 years old and say 'repeat this continuously and your health is forever good' thus, (LEV) you can live a 1000 years old with the body of a 25-year old.
CR is capable of increasing maximum lifespan, chronological lifespan because it reduces all types of damages - during the whole lifespan, increasing health span. That - is what we need. LEV is that, but we don't know what happens after MLSP is surpassed and compression of morbidity becomes extreme. We will we be 100% healthy and die suddenly the next day; it's not supposed to happen but all things point towards that because morbidity compression is very real (as the redox improves, compression increases, but MLSP can be increased too - at the same time that there is compression. That's what I fear, this extreme compression can mean that life ends from one day to the next, yet you felt 'perfect' yesterday).
If reversal to a 30year old body 'in repetition' means no morbidity ever, then LEV should be possible because morbidity would be ruled out by having a Young body forever - but does it really pan out like out, I'm not so sure...CR studies disprove that and show that morbidity and phase of 'going down' is always there no matter how much you slow down/reverse the damage.
Perhaps, yet again, explaingin the 'epigenetic program' is 'already too Advanced/changed'...and you can't change it, so morbidity would still apply despite damage reduction.
So many questions and dead end answers : )
Erythrocyte plasma membrane redox system may determine maximum life span.
1. http://www.sciencedirect.com/science/article/pii/S0306987710005268
Ps:
I found an incredible study in parasited nematode S.ratti, like C.Elegans, that disproves maximum lifespan in species (anomalous), disproves compression morbidity as inescapable and, indeed, shows that LEV is 100% True and thus, LEV **could very much give a 1000 year human lifespan ** (we needed an example in a Real living organism to prove LEV):
''Gardner, Viney and Gems.
Limitations of lifespan by aging, as opposed to some other extrinsic cause of mortality (e.g., predation or disease),
may be established by testing for the occurence of an exponential increase in mortality rate with increasing age
(Watcher and Finch, 1997). From plots of In(mortality rate) against age, the IMR [Initial Mortality Rate]
and the Gompertz exponential function can be calculated. The latter may be expressed in a form that is easier
to grasp; the Mortality Rate of Doubling Time (MRDT). These mortality parameters for free-living S.ratti females
and parasitic S.ratti females are described below.
Age-specific mortality S.ratti free-living adult females
The survival of free-living S.ratti females under optimized S.ratti culture conditions are shown in Figure 20.2B.
This shows that its maximum lifespan is 4.5 days...
...The mean lifespan of C.elegans hermaphrodites under either condition (S.ratti conditions: 7.7 days, monoxenic: 11.2 days)
was substantially longer than that of S.ratti (3.0 days)...
For [free-living] S.ratti the MRDT was lower and the IMR higher (0.8 days; 0.025 days, respectively) than C.elegans.
...***Overall these findings imply that S.ratti is shorter lived than C.elegans because (a) it is more frail,
as reflected by higher IMR, and (b) it ages more quickly, as reflected by a lower MRDT.
*****************
Age-specific mortality S.ratti **parasitic** females
In S.ratti parasitic females, maximum lifespan is ***403 days***, which is ***80 times*** greater than the 5-day lifespan of free-living [S.ratti] females.
***The parasitic females underwent and exponential increase in mortality rate with age, thereby showing that senescence was occuring.
The IMR of parasitic females was 0.0056 days, which is 25% of that of free-living females. The MRDT of the parasitic females was 22.7 days,
which is **some 30 times** longer than that of free-living females. Overall, this comparison of the parasitic and free-living females implies
that free-living [females] morphs are shorter-lived
****due to their increased frailty (as reflected by the greater IMR, initial mortality rate) and a faster
rate of aging (as reflected by a lower MRDT, mortality rate of doubling time)*****.
S.ratti is the first parasitic nematode in which occurence of demographic senescence has been demonstrated in the laboratory.
*****************
''
This study is incredible because it is capable of showing that specie maximum lifespan is an anomaly (I mean an 80-FOLD extension of maximum lifespan by parasite infection, Nothing has done that ever!) and can definitely be uncoupled from aging : that there is no such thing as a maximum lifespan. Neither for humans.
And, thus, compression of morbidity - will happen, but - Not - if we reach LEV and allow our body to remain in a state of youth (a continuously 25-year old body Is Essential) and youth-like health (I'm not talking about a 'healthy old person' (no such thing, they show structural damage but adapted to it to be 'healthily liveable')...I'm talking about a 'healthy biologically 'young' person' (no structural damage) forever long it is needed to postpone aging continuously, which would equal to immortality/Eternal life) Compression of morbidity is only when the specie's individual is on a 'regular course'....otherwise, such as is the case with SENS, it is NOT a regular course anymore, and MLSP can be modulated to be increased - if morbidity (MRDT and, especially, IMR) is nullified; which would allow eternal life. Thus, MLSP (anomalous), but HLSP (Health Lifespan) = IMR + MRDT = any MLSP.
Aging is clearly a mixture of damage and program. However that is not really as important as actually getting the research done and testing these interventions. This is why our project is engaged in this work right now and why we are trying to raise the funds to do so. I urge you to consider donating to the cause if you have not done so then we can start getting answers and putting repair strategy to the test!