The Growth of Programmed Aging Theories in the Research Community
There are two important battles in the matter of aging research. The first is to convince people that aging should be treated as a medical condition at all. This has, finally, largely been won within the scientific community, or at least those parts of it that matter, but is still very much an ongoing concern when it comes to the public and potential sources of large-scale funding. The second battle is between the classes of theory of aging that determine what types of therapy should be developed. On the one hand there is the prevailing majority view of aging as the result of accumulated molecular damage to cells and tissues, that in turn produces all sorts of further harm and reactions in cellular behavior. That means therapies should aim to repair that damage, though, sadly, most researchers who hold to the damage theories of aging are in fact more focused on therapies that only slow down the rate at which damage accumulates. On the other hand, there is the growing minority view of aging as an evolved program in which epigenetic changes cause changes in cellular behavior that in turn lead to the accumulation of damage. There is a lot of debate within the programmed aging community as to the nature of this program and its relationship with evolutionary theories on aging, but regardless of that, the basic concept implies that repair of damage is marginal and therapies should try to revert epigenetic changes that occur with age, such as via the use of drugs or gene therapies to alter cell behavior.
So we have two views of aging that stand in opposition to one another because the strategy for development of therapies that emerges from each is opposed. The yet-to-be-developed therapies thought to be effective in one paradigm are expected to be marginal in the other - and that matters greatly for those of us likely to age to death if the wrong lines of development come to dominate the field for too long. If you think that damage is the first cause of aging, then tinkering with epigenetics is evidently going to do little good. If you think that epigenetic changes are the first cause of aging, then repairing the damage without changing cellular operations is not the way to go. Interestingly, I think that the past decade of growth in publications and discussion of programmed aging has its roots in changes outside the scientific community; that it has a lot to do with the widespread adoption of automated translation technologies, as these have enabled closer ties between the Russian and English language aging research communities and their supporting network of advocates and funding sources. The Russian aging research community is much more in favor of programmed aging, and provides the necessary critical mass of thought and work to bring programmed aging to a larger audience in the English-language community.
For my part, I think that the best argument against programmed aging is that there are forms of metabolic waste that the body cannot effectively break down. Components of lipofuscin and glucosepane cross-links for example. You can change all the epigenetics you want, assuming a way can be found to force cells into a replica of their youthful state, but that won't enable them to clear out that harmful waste. Further, there is plentiful evidence for higher levels of these metabolic waste compounds to contribute directly to age-related pathologies, and it would be hard to postulate a way for that to happen with it also producing epigenetic changes in cells. These two points interact to strongly suggest that programmed aging is incorrect. I'm also of the mind that this debate will be settled fairly conclusively within the next decade, as the first therapies resulting from both sides are deployed. My expectation is that efforts to repair damage will produce robust rejuvenation and that efforts to restore youthful epigenetic patterns and signaling in cell environments will, where successful, produce results that look a lot like those achieved via stem cell therapies to date - putting damaged cells back to work, but not repairing underlying causes of aging. Regeneration, to some degree, but not rejuvenation. These are quite different outcomes, and should be clearly distinct from one another once biomarkers of aging are used in their assessment. At the moment, however, I suspect there is a quite of lot of confusing regeneration for rejuvenation taking place.
Twenty years ago, I first started writing that aging is something the body does to itself, a body function, rather than deterioration or loss of function. Journals would not even send my submission out for peer review. The conflict with prevailling evolutionary theory was just too deep. But in the interim, the evidence has continued to pile up, and many medical researchers have taken the message to heart in a practical way, setting aside the evolutionary question and just pursuing approaches that seem to work. The most promising developments in anti-aging medicine involve changing the signaling environment rather than trying to "fix what goes wrong" with the body.
My popular book exploring the evolutionary origins of aging (and implications for medical science) came out in June, and an academic version of the same content came out in October. Gandhi taught me, "First they ignore you, then they laugh at you, then they fight you, then you win." The paradigm of programmed aging passed this year from stage 2 to stage 3, with prominent articles arguing against the possibility of programmed aging. Current Aging Sciences devoted a full issue to the question. I welcome the discussion. This is a debate that colleagues and I have sought to initiate for many years. There are powerful theoretical arguments on one side, and diverse empirical observations on the other. The scientific community will eventually opt for empiricism, but not until theory digs in its heels and fights to the death. A basic principle of evolution is at stake, and many theorists will rise to defend the basis of their life work; but a re-evaluation of basic evolutionary theory is long overdue. The idea that fitness consists in reproducing as fast as possible is no longer tenable. For plants, this may be approximately true. But animal populations cannot afford to reproduce at a pace faster than the base of their food chain can support. Animals that exploit their food supply unsustainably will starve their own children, and there is no evolutionary future in that. This is a principle that links together entire ecologies, and the foundation of evolutionary theory will have to be rewritten to take it into account.
For many years, I put forward the argument that programmed aging means there are genes that serve no other purpose than to hasten our death, and that medical research should be targeting the products of those genes. But in recent years, epigenetics has eclipsed genetics as the major theme in molecular biology. Everything that happens in the body is determined by which genes are expressed where and when. The vast majority of our DNA is devoted not to coding of proteins but to promoter and repressor regions that control gene expression with exquisite subtlety. There has been a growing recognition of aging as an epigenetic program. As we get older, genes that protect us are dialed down, and genes for inflammation and apoptosis are dialed up so high that healthy tissue is being destroyed. Many epigenetic scientists have discovered this, and they find it natural to see aging as a programmed phenomenon.
A few years ago, I wrote about transcription factors as the key to aging. At first blush, it seems that an epigenetic program is just as amenable to pharmaceutical intervention as a genetic program. Transcription factors bind to DNA and turn whole suites of genes on and off in a coordinated way. This summer, I had a chance to work in a worm genetics lab and consult closely with people who know the experimental details. I learned that there is no clear line between functional proteins and transcription factors, that many proteins have multiple functions, and that metabolites feed back to control gene expression. I still believe that there are one or more aging clocks that inform the body of an age-appropriate metabolic state, and synchronize the aging of different systems. Telomere length is one such clock. If we can reset an aging clock, the body will repair and clean itself up. If we can reset several clocks, the body may be able to restore itself to a younger state. But I recognize the possibility that the clock is diffused through the detailed epigenetic status of a trillion cells, and may be beyond the reach of foreseeable technology. Short of resetting the aging clock, there are several technologies just over the horizon that should offer substantial life extension benefit. I believe the best prospects are senolytics (ridding the body of senescent cells), telomerase activators (rejuvenating old stem cells), and adjusting blood levels of key hormones and cytokines that increase or decrease with age.
"But animal populations cannot afford to reproduce at a pace faster than the base of their food chain can support. Animals that exploit their food supply unsustainably will starve their own children, and there is no evolutionary future in that. This is a principle that links together entire ecologies, and the foundation of evolutionary theory will have to be rewritten to take it into account."
Nope, evolution doesn't work that way. The unit of selection is the individual, not the population. If you have a population with a low fertily rate and inside it an individual with a high fertility rate, then that individual has an advantage to its peers, and its genes related to fertility will spread faster than those of its peers. It's that simple. Even if a low fertility rate would be better for the population as a whole, it will not happen. Simply, population dynamics don't work that way.
Consider for example sex ratios. The better for the population would be to have few males and a lot of females. That way, progeny is maximized wrt resource use. Instead of that, we have a 50/50 ratio in most species, because that is what happens when individuals can benefit instead of the group.
You can have group selection only in special cases, for example, when the population is a family group competing against other family groups and there is not much reproduction inter or intra groups. For example, ant colonies. But that's not the case for humans.
@Antonio: I didn't understand what you mean with: "Consider for example sex ratios. The better for the population would be to have few males and a lot of females. That way, progeny is maximized wrt resource use. Instead of that, we have a 50/50 ratio in most species, because that is what happens when individuals can benefit instead of the group."
This is the worst example I've ever seen. He's making trouble for us, others. The world is becoming overcrowded. I would prefer to live in a world with few people so that infectious disease doesn't spread and individuals could live extremely long lives:
I suspect that most people arguing programmed aging at this point do so as a way to butress an intelligent design viewpoint.
No, niet, nein, non, ... the world is not becoming overcrowded and never has been. It has been discussed many times here. The data says just the opposite, we are facing a serious underpopulation problem in the near future.
And no, niet, nein, non, ... effect of infectious diseases on longevity was much bigger when world population was much smaller.
And anyway all of that has nothing to do with the reason why most sexual species have an almost an exact 50/50 ratio between sexes.
There will not be overcrowded world because we will have clean energy, artificial meat, clean water, flying cars (more space left in citys). But I think that what the man who donated semen to 1000 woman was unwise in many ways.
Who needs data when you got belief?
What a waste of time...
My 2 cents, I am both in shock and understanding of people's fears concerning the future. But some are unfounded or exaggerated.
They are not necessarily right but I, can understand, why people would fear overcrowding - I think it stems from the fact that humans population has grown considerably in the span a single century.
Earthly Population was barely less than a 1 Billion, and in the span of hundreds years there we are to
7 Billion or so. In a sense, it's the multiplication factor that they fear (look at China, India or Russia, countries with massive population and that attained them in the last 100 years), not so much the Billion factor. But, in a reality, like Antonio said - we're Underpopulated on Earth. People immediately think that the Earth can't stand our 7 Billion presence (as said that we are depleting Earth's resources faster than it can rebuild them - and that we multiply in numbers faster than it can recoup them too).
Again, that's mostly false. Yes, we are taxing it more than before - but nowhere near in the catastrophic impression that people make it out to be. Earth - can - take it, trust me on that.
Some species are in the hundreds of billions, the total number of animals on Earth is in over trillions,
there is lots of free space and huge swaths of nothing areas (I live in Canada and it's a huge country with tons of inhabited by human Forests for thounsand of miles (except wild animals in there), same in the USA, tons of inhabited areas. Same in Europe and Asia (Russia, Immense lands of nothing and forests, Himalayas Tibet - living in the Heights/mountains, lots of 'high' empty space in the sky), or Africa (huge deserts and underground caves), Not even counting the Abyss underwold below water (people could live deep down miles underwater, it's a Mega-Huge world beneath our feet). Want to live near the Earth's core a thousand sediment crusts layers below (population have tried before and some did well in cavern like areas deep in the earth) ? Even if Earth could not take it anymore, we will find ways - living on another planet (perhaps Mars or the Moon... who knows..we might need to move but we might not).
There, is, a solution. What is more important is to cure death then we can solve all these lesser important 'ethical' problems (curing death should be the most important goal of all, when we can live long lives 'as done and accomplished' we can then decide what happens next (ethically speaking)) Some are against that and want to block it immediately thinking it's dumb and without thinking (or should we say without adding 'ethic' to it - first, as if ethic should guide immediately on whether we should or not extend lifespan indifinetly). I understand that sometimes this thinking/rationalizing helps greatly - but it's not going to happen for a very long time - if we're dead anyways. Making this whole 'thinking/rationalizing' in a 'ethically-inclined' way quite futile on the subject of life or death.
Currently demographics show that now there is a reversal effect where there is a reduction of birthing and as such population could become underpopulated in the future (women making less and less children),
thus there would not be enough population replacement - old people would be the only ones left and they would die at a certain point (the population then shrinks). What is sure is we are not there yet - there is 7 billion strong of us...so it's not yet a big problem - but later it will be if demographic natality keeps on dropping and men/women don't make any children anymore. Thankfully there are certain areas that keep the numbers strong, for now (such as Africa(n countries) and Asia(n countries like China, even there they had to 'curfew' their overdemographics (being a billion) a bit and now it will most likely go down).
Hi Norse !
The bit that Antonio explained is that an evolutionary-wise a ratio favoring more females per male is
indeed better and the reason for that; is because females are the birthing sex and males have the capacity for Male Hypergamy/Polygamy (a single man can make many children - by many females, species show that deeply - like lemurs or rats - male lemurs that have the largest testicules, are having the most sex and the highest reproduction (1 single female rat can make Millions of rats - it's that freaky and it's why it's one of the most 'proliferative' animal in all the wold (the vermin spreads like coacroaches (who also reproduce millions of times, it's also why you would find vermin rats in the Ship Decks during New World (Canada/US/Latin America) Colonization and how the rat proliferation spread all over the world by bringing it in the ships from Europe - from your country actually Norwege (Norvegian Rat : Rattus norvegicus)..), 1 Single Male that can make an entire millions-colonny basically - as he has sex with thousands upon thousands of females - which all of them birth - multiply that and you understand why evolution favors the female sex being higher in number and the male in low number. The females are Necessary for birth - males too - but Less so, a group can't survive long with a single female and tons of males - while a group will survive longer with many females and a single male. And, that's because that male will give birth to Each of these females (Increasing the Odds of Survival By Increased Birthing (from Total Number of Pregnant Females) and Reduction of Loss of Children at birth (since More Females are Pregnant, less odds of loss), while inversely, the tons of males will fight for that Single Female - whom as herself alone/her sole body capacity to give birth - thus a 'limited birthing' potential group (a single female 'takes time' to give birth...all the while these males have no Other female to give birth - at the same time) and thus, a stronger chance for extinction (remember that single female may not even be Capable of give birth - you have a big problem - there are no Other Females (who can give birth at the same time or subsequently. For a group of tons of males and 1 'defective' female - it's Population Suicide/Extinction). Not only that, males are disposable since of sperm regeneration, 1 single male bedding many females - you don't Need Many males, you just need One that is sexually 'healthy' enough). And also, males again disposable because of lesser genetic/less genetically stable than females (evolution favors female chromosomal arrangement).
The Double X females chromosomes is a better and more genetically stable setup than the males 'X' and 'y' chromosomes arrangement (the male 'y' chromosome is a stripped version (contains less DNA matter/thus less adapting possibility) and compromises the DNA stability). It's a clear indication that evolution chooses females first, and ''unchooses'' males' for 'disposability' by compromising it and as such 'less important' than females (it did that to our male chromosomes). It's also why women live longer than men (because they carry double-X chromosomes while men carry a small 'unstable/loose 'y' chromosome with a big stable X 'female' chromsome - women got two of them - this increases stability and longevity (seen in women who face less oxidative stress, and not just women, other animals too like mice or rats females who live longer than the males - because of double-X chromosomes)).
Don't ask yourself why there are 9 Centenarian Women for 1 Centenarian Man. That's the answer.
Why they do women reach a 100 almost 10-times likelier than men...chromosomes and evolutionary selection of females. With that said, females that live longer and longer, are selected - Against evolution and that's because there is trade-off in evolution. Evolution is about a compromise between longevity genes resources vs sexual genes resources, as such women who live longer produce less children - they are 'eating away' the sexual resources (the sexual resoueces are diverted/relocated towards longevity gene/DNA maintenance - make females that are less 'birthing' capable and prone/less sexually active also).
This is Fact :
Centenarian women - make less - children than shorted-live women. about 1 child for centenarian women, while shorter-lived women can make 1.5 children or more. Yes, there are cases where the centenarian women made many children - that is not a norm - and a special case (basically an outlier). There - is - a cost to have progeny and also for hypergamy/polygamy (hypergamous species are millions in progeny and also generally, short lived -this is seen in a study that looked at lizards, the shortest lived lizards were super sexually active and with the higest population - while the longest-lived who live 100 years like the tuatara reptile were abstaining sex and no-or-low birthing).
A sexual cost/sexual resources. This is seen in rats who divert longevity genes resources towards sexual reproduction performance - at the cost of a short life (rats live barely 5 years, yet they can make millions in progeny). This also seen in nematodes, C.Elegans who live much longer if infertile and sexually amorph (the reason is, sperm, gonadal and hormones are - linked - to developmental growth, basically the whole IGF/mTOR/PIK3 pathway decided the metabolic speed and the speed of organismal 'growth' (which is tied also to cell cycling and proliferation)), the Sexual Maturation (when an animal reaches sexual capability oftenly in adult age (which the onset of the downward slope to death)). The purpose of the animal is 'done' when he/she reached sexual maturation and then, procreates - as such the downward slopes starts there and the animal dies (quickly in rats for example, who don'T live much longer after being sexually mature). The mTOR pathway connected with the IGF with the hormones (testosterone, estrogen) regulate the speed of developmental growht (long-lived animals have intense brain plasticizing because of very late 'puberty' sexual maturity (seen in naked mole rats who have protracted brain development over 20 years and are sexually 'impubert' for a long time like humans, in humans it takes at least some 10-13 years before females can have children, in naked mole rats same thing, in elephants, longe-lived apes or long-lived bowhead whales or long-lived clams, same thing again). This sexual reproduction system is very costly by increasing germ stem cell compartment demand/increases sexual resource demand on reproductive germ cells. C.elegans nemated show that clearly in their lifespan being shorten the instant you touch the sexual germ cells, it's energetically/cellularly costly endeavor to have progeny.
Also, in humans, a study proved it :
women who were high gravidity (4 children/pregnancies or more) had higher mitochondrial lesions in their mitochondrial DNA then low gravidity women (1 child/pregnancy or less). It's very costly on their life, to women, to have kids (so of course when I see women making Many Kids (in huge families like in the old days of 15 kids...) I wonder how much damage she took to make these children it's a very altruistic and kind gesture of the mother of course (she is killing herself giving birth to more populace to make specie continue).
'' I would prefer to live in a world with few people so that infectious disease doesn't spread and individuals could live extremely long lives:''
I understand you... I think we have to strike a middle-ground where there is 'enough' population birthing (not so low we become extinct/all old 'single' people and no more couples). But, it's true a lower number does help to reduce infection spread (you don'T want the Whole populace to be contaminated) - still as Antonio said, infection can spread more rapidly in a smaller populace because of small number - faster reaching of total number. It takes a long time to spread in large populace. But, once the 'ball gets rolling' and 'spreading gets spreading' it can be devastating, Antonio could say so, with the Spanish Influenza taht killed Millions of people when it propagated like a zombie virus all over the place. Same for Mayan, Aztec, Incas, Toltec and Olmec population in Latin Ameriac who were decimated by
Spaniard Conquistadors in 1500s, by importing Spanish rats vermine and Spanish virus diseases that killed them by infective propagation. Same thing in Canada or US, with rats all over and small pox (the diseases were inside the Ships/boats and the colonizers/ship crew/in their bed sheets they gave as offerings (some times people think there were 'willfully' given 'to poison and infect them' as a sure way to kill them all), that killed millions of North American Aboriginal First Nation Amerindian/American Red Natives (the diseases virus were more deadly than the wars).
Just a 2 cent.
Late bloomers and baby boomers: ecological drivers of longevity in squamates and the tuatara
''Squamates in high latitudes and cold regions live for longer, probably because a shorter season of activity translates to slower development, older age at first reproduction and hence to increased longevity. Individuals live longer in captivity than in the wild. Herbivorous and omnivorous squamates live for longer than carnivorous ones. We postulate that low-quality nutrition
***reduces growth rates***, promotes a ****relative decline in reproductive rates*** and thus prolongs life.
Our results support key predictions from life-history theory and suggest that ***reproducing more slowly*** and at older ages, being herbivorous and, plausibly, ***lowering metabolism***, result in ***increased longevity***.''
sexual reproduction = speed of metabolism is tied to it (although it is not a 1:1 thing, as seen in an outlier like the Infected Salmon Fish who live 13 years and is sexually capable for that long, while the uninfected salmon fish lives 3 or 4 years and becomes sexually senescent quickly. This means that there are 'ratios' if you will between longevity and sexual reproduction; still, this shows that sexual metabolism, sexual resources, and anti-oxidative longevity genes can be uncoupled (certain nematodes can hold sexual activitiy and live longer - too, it's quite complicated and as such, it's just a 'trend' but we are changing that. Still, the study of women getting multiple pregnancies and showing increased mitochondrial DNA lesions each subsequent pregnancy, it's a pure proof that the offsprings/progeny are very costly energetically and increases oxidative stress - by removing/having less anti-oxidative resources - relocated as sexual resources for sexual/progenic performance).
The only way - like the infected salmon - is to sexually capability, not become sexually senescent (seen in men and women who face andropause and menopause (when sexual hormones dip at 50 years old or so), this creates tons of problems and increased oxidatve stress (women who have menopause face heart attacks...because of estrogen loss...and because estrongen activate estrogenic telomerase receptors, without their estrogen, telomerase drops thus their telomeres erode faster after menopause, while men also, with andropause, since testosterone is converted to estrogen in men's bodies by aromatase enzyme, as such they too have a loss of telomerase acting on their telomeres and face more diseases as andropause sets in. One study showed that male and female centenarians - where, still, sexually capable - and that was because their maintained - higher levels - of sexual hormones (they have lower IGF1 growth hormone levels but they maintain sexual hormones like estrogen while people who die younger get quicker into menopause or andropause). The message being : keep your body young biologically - and sexually capable (enough) - just don'T over do it/sex machine/making a family of 15 kids for women/you will abuse your sexual system resources/increase oxidative stress by loss of telomerase/redox loss (in the sex department, keep that libido at 'low-key' but not extinct either, be sexually active 'enough' that's it the best balance of longevity vs sexual activity). You want to push back the downward slope as far as possible (that means pushing back menopause and andropause until your dead, like sexually-capable centenarians do).
@CAN: what about masturbation in both sexes? I have read various sources but cannot come to a conclusion. Reduces it lifespan? I think it does in males becaus of sperm production has to renew.
I also agree that no 1 goal for all intelligent people shold be to extend their lives. I like Minsky saying he has thousands of years of work to do if given the chance. We as a society are early in development when other species lives longer than the smartest species, humans.
The guy that you quote writes like a dogmatic - it seems nothing could persuade him that he is wrong. His theory about aging is that it happens 'for the good of the specie'. Evolutionary obstacles aside, the clearest argument that I have read against programmed aging is that, among all possible kinds of genetic defects ever recorded, there were zero cases where that particular genetic mechanism was found to be broken. How so?
Mastur... same thing. Some studies want to pinpoint the actual 'physical exerise' as the true 'aging' factor in sexual reproduction (not the sperm regeneration which would be very low-cost, but the 'sexual activivity' is much higher cost...yeah 'going up and down' as 'sexy exercise' is apparently costly (exercise is good for you body, so of course having sex would increase fitness - but it seems otherwise. I wager that only low dose sex or mastu... is good because it demads less on - both - your sexual organs and on your body (the exercise is hard on the body... your heart beats extremely fast during sex - all of this combines to accelerated 'use/used-up body' (wear and tear is accelerated), athletes demonstrate that and some studies also showed that only medium - to - low exercise was the most benefitial - not extreme exercise (seen in athletes who push themselves to break point/physical exhaustion).
Sex is Physically Exhausting (almost much more than going for a 'jogg run', your heart beats so fast - this is a clear sign your metabolism increases during sex (and increased metabolism is correlated with a short-life, animals have found ways to get aroud that problem though (such as bats and small dogs, who live very-long lives and have accelerated metabolism : they reorganise fat-usage and carb-usage (their brown and white adipose tissue produce an excess of UCP proteins and (Uncoupling Proteins that disengagne proton pump-ATP production by electron from the ETC (Electron Transport Chain) like a valve and HSPs Heat-Shock Proteins Chaperones (refold unfolded/damaged proteins) which protect them from energy overspending by fast metabolism (thus they protect their proteasomal function (they remove the junk - despite having faster metabolism. One studie showed that HSPs activity is actually correlated to maximal lifespan). When you have sex your body know it's 'demanding' it turns on fat-burning by activitating metabolism/fast burning through BAT/WAT UCPs, PGC-1a and HSPs.
So to answer : Yes, mastu...though good - but only in low dose. It amounts to basically having sex - but the calorie burn count smaller - so is the emotional and physical impact (shaking your hand mast.. vs whole body action in sex), sex is Real..mast..is not, it,s basically 'make belief' 'self-sex' using your own fantasies imagination. You have to find ways to get there (The G spot for women and for men..well not sure what's it called), when you mast...
Sex is more demanding on all body resources. Mast.. is a bit less.
''Reduces it lifespan? I think it does in males becaus of sperm production has to renew.''
Exactly, sperm production and regeneration is not something 'free', it - has - a cost - and thus affects the balance between life/longevity (resources) vs sex/reproduction (resources). It's very to argue with a study that showed that women were 'aging' in 'Acceleration' by having - more kids (they accumulated 8-oxo-dG lesions in mitochondrial DNA as pregnancies were repeated). So, same thing for women who mastur... although, of course, they are 'pregnant' but just sexually capable that's a large difference. The Pregnancy is greatly costly, while sexual intercourse or mastur... is too - but less so.
Don't stop that's the main point, you want to avoid andropause - all men must keep their testosterones level (mastub...helps for that, it improves testosterones levels; but the best effect is when you do it - seldomly/sparingly/occasionnaly when you feel 'the urge/your body is telling - yes now, I want it - I am ready and 'recuperated' (you 'Give a Chance' to your body to regenerate and recuperate from your last mast.. session)...listen to your body don't go against it (if your sexual organ is 'spent' and you feel ill/your health degrades, you know you went too far on the mast..thing).
''I like Minsky saying he has thousands of years of work to do if given the chance.''
I second that, very true...it might sound to all the fatalists and hysterical alarmists : Boringggg..
a thousand years of working is dead boring - all bore - no action (or in this case no mastur...action),
''All Work. No Play. Makes Jack A Dull Boy''. I think for some people their work is everything but it's so pleasing it's not 'work' it's like 'playing' basically..it's effortless and so natural they could do until death. You have to Love your work, deeply for that - because a 1000 years of it will kill you dead of bore or something else. In my case, I think it's almost a 'duty' if you will of 'finding something' in life to love..or do - just Occupy yourself, make New Projects Always (even if you fell you Did Everything in this world - it's boring now - you have to Unlearn What You know We call that 'becoming a child again' (as old people come back to like a 'child' joyu and simplicity since they will die soon and the rest is not important, just the 'simplicity and innoncence' in life (like an innocent child who is 'untarnished' 'unaffected' 'uninfluenced' 'uneducated' 'unbiased' 'unopionated 'new'...) somehow someway...you Have To...you are gonna live a 1000 years , it's long, very long.
Hi Jamie !
''Evolutionary obstacles aside, the clearest argument that I have read against programmed aging is that, among all possible kinds of genetic defects ever recorded, there were zero cases where that particular genetic mechanism was found to be broken. How so?''
Just 2 cent, first I have to say that programmed aging and damage-accumulation aging are very 'vast' and intermingling and so it's very hard to be absolutely accurate since they are both (co)independent and (co)inter-dependant - at the same time. Aging is complex like that. The difficulty lies into thinking is it one or the other, one more Causal than Correlative (of the other?) or both?. It's not one or the other - it's both, together in parallel at the same time feeding off of each other - and Some More. Pretty much like the Yin and the Yan sign, they compliment each other, so does programmed aging and damage accrual aging.
''...the clearest argument that I have read against programmed aging is that, among all possible kinds of genetic defects ever recorded, there were zero cases where that particular genetic mechanism was found to be broken. How so?''
I believe it is because genes can actually be turned on or off just like a switch mechanism - doesn't mean they are defective - they are just off (or on). This mechanism is related to programmed epigenetic aging : it is the donation of methyl group to the gene dna area (like CpG-rich/poor Islands loci in DNA), the methyl group then can methylate the gene - this is turn can create 'gene silencing' (especially visible in children who have higher gene silencing because of higher methylation/more methylated methylome/higher telomeres = higher methyl count) as we age we become demthylated (global demethylation in precise areas, while certain other areas that were demethylated (for a good reason (like not activating cancer promoting genes (p53, p16, p21, INT-6, TNF and others)) they become hyper methylated/while protective redox genes become demethylated (they are turned off) (as such inflammation 'begins' and the organisms 'ages' as it accumulates so much insults (which alter the telomeres, which they alter the cell cycling dynamics (which accelerate entry into senenscence (the Spontaneous Stress-Induced Senescence or Oncogene-induced Senescence, not the Replicative Senescence (Hayflick limit) which this last one is cause by time serial passaging/cell cycles count over the life of a human)). Aging is far more complex than we think, it's not just 'damage accumulation' or just 'programmation thing', it's a very deep orchestration on so many redundant layers, it's like a ratmaze for us - impossible to untangle - it's a maze in all dimensions. And we're caught in it like a little fly in a spider 3d-web - we're doomed...