Speaking of self-repair, here’s a fascinating new finding from Malin Hernebring in Sweden. Here’s the technical paper, from a few years ago; it’s part of Hernebring’s Ph.D. thesis work. (Via Richard Dawkins’s site.)
As we age, our cells gradually decay; the DNA stays relatively intact, but proteins degrade with time. This is a big part of the aging process, leading to wrinkled skin as well as more serious consequences. When you think about it a bit, that raises a puzzle. A newborn baby arises out of the cells of its parents. So if the proteins simply decay without repair, every generation would get handed down a degraded set of proteins. At some point, therefore, there has to be some repair job, so that the baby gets fully functioning proteins.
If this idea is right, you might guess that the repairs happen at the level of ovum and sperm; maybe when these cells are created, extra effort goes into tuning up their proteins into working order. But the new research says no — it’s actually after conception that the clean-up crew arrives. The newly conceived embryo consists of stem cells that soon begin differentiating themselves into the different kind of mature cells. It turns out that it’s during this differentiation process that proteasomes go to work, breaking down the damaged proteins and generally tuning up the engine. (Maybe this is when the soul is implanted in the embryo?)
The next obvious question is: why can’t these cellular clean-up crews be active all the time? There are clear implications for studies of (and therapeutic approaches to) aging. Nature wants all the individual animal organisms to die, making room for new generations; but there’s no reason we have to go along with the plan.
Along somewhat similar lines see:
http://www.sciencedaily.com/releases/2011/09/110920163215.htm
“Researchers have shown they can reverse the aging process for human adult stem cells, which are responsible for helping old or damaged tissues regenerate. The findings could lead to medical treatments that may repair a host of ailments that occur because of tissue damage as people age.”
Now, if I can just hold on long enough 😉
Cool research, but:
“Nature wants all the individual animal organisms to die, making room for new generations”
*cringe*
The idea that we die for the good of the species (by making room for the youngins) isn’t really accurate. We die because nature doesn’t care. More precisely, nature has us live as long as needed to make babies, and after that, with allowances for raising said babies, it couldn’t care less. Any adaptation that let us live longer would have been wasting energy better spent baby-making.
“the DNA stays relatively intact, but proteins degrade with time”
i dont think that quite right,
proteins are continually recycled.
as we age for each cell generation the DNA telomere gets continually shorter
I have to echo the *cringe*. Neither nature nor evolution is an agent, and it is rarely useful to model either as one. Products of evolution can be, and it can be extremely useful to talk about their wants (conscious or not) in terms of what has been successful.
I think the cells are conserving energy and work by only revamping the cells that have made a baby instead of revamping every cell. Working smart instead of working hard.
Oh Science !
I hope we find a cure to aging soon thanks to stem cell research. This disease touching 6.3 billion of the population is quite troublesome.
Hopefully great people like Mr Aubrey De Gray will help change the minds about immortality and why we should cure aging.
“At some point, therefore, there has to be some repair job, so that the baby gets fully functioning proteins.”
Where does one think the fresh proteins in offspring come from? From the parents? The genetic endowment in the DNA in the chromosomes code for manufacturing proteins from scratch (or from suitably simple molecules that aren’t complex enough to be easily damaged, such as amino acids). The ‘repair job’ is the act of reproduction itself: throw out the old, age-damaged and contaminated models (typically the female and male parents who have contributed their genetic heritage to the offspring) and start over again from the top, that is, from the least complex stage in the most compact possible package (the fertilized egg or its immediate antecedents) that contains all the information necessary to deploy a fully-functional adult. Repeat as often as opportunity and resources permit before age-related degradation prevents reproductive success.
Death is a crucial function of life.
Anchor,
You say that “[d]eath is a crucial function of life.”
But it doesn’t have to be, does it? Do you think there is some fundamental reason why we can’t come up with a repair job that doesn’t involve reproduction in the sense you describe, and death?
One may have religious, moral, ethical or philosophical complaints — which I wouldn’t agree with anyway — but isn’t finding an alternative way to implement such repair “simply” a matter of gaining greater understanding and then engineering a solution?
?!
What percentage of the proteins (or even the DNA) in an adult human (or a newborn baby, for that matter) originate in the parents? And how did the marvellous Mother Nature squeeze them all into the gamete?
According to the usual evolutionary thinking, the purpose of death is not to ‘make room’, nor does it lose interest after making babies. It’s a mechanism for resisting diseases and parasites. Pathogens usually have very short life cycles and so evolve and adapt rapidly to break our immune defences. We can’t keep up, with our much slower reproductive cycle, and can only build in so much protection. It’s like every cell in our bodies is set with a combination lock, that the immune system uses to tell friend from intruder. It only takes so long for the pathogens to search through all the combinations. And the body can’t change the combinations on all its cells simultaneously – there would be an awkward period part way through, where bits of the immune system and bits of the body had mismatched codes and would attack one another. So evolution achieves the effect by changing the combination in one cell and then throwing the rest of the body away – the one cell being multiplied to make a new body. It’s shockingly wasteful and inefficient, but effective. Better designs are no doubt possible, but not easy to evolve by blind exploration.
You don’t want old and out-of-date models hanging around as they provide a reservoir for diseases – just as immunisation programmes have to cover a big enough proportion of the population or the unimmunised act as a reservoir for new epidemics. Hence death is to some extent programmed in.
If we were to somehow engineer our immune systems to eliminate all disease, then immortality would evenually evolve naturally. (Continuing to have babies is more efficient than taking a 16-year break every generation to grow a new body.) Conversely, if we turn off aging and death without first dealing with disease, we will face ever-more-precisely adapted plagues that circumvent all our defences, one by one. It’s like the story of antibiotic-resistance – it would start off as a miracle story to banish death forever, until you realise that over-use has shortened its time of effectiveness, and ‘forever’ isn’t as long as you thought. You have to keep moving.
Rejuvenating cells is certainly a useful trick to know, and undoubtedly will be part of the ultimate solution. But a better trick would be to be able to switch immune system recognition signals smoothly, mid-life.
@6: Oh, he’s called Aubrey, now, is he?
@#8 Mike: “Do you think there is some fundamental reason why we can’t come up with a repair job that doesn’t involve reproduction in the sense you describe, and death?”
No. Does the sense of what I describe suggest that I think we can’t?
“One may have religious, moral, ethical or philosophical complaints — which I wouldn’t agree with anyway — but isn’t finding an alternative way to implement such repair “simply” a matter of gaining greater understanding and then engineering a solution?”
Sure. Why not? (Without the slightest religious, moral, ethical or philosophical compunctions, even if I did see any relevance in applying those arbitrary filters when mentioning the D-word).
There’s an encouraging difference between how nature does something and how human ingenuity (which one must acknowledge ultimately is a product of natural selection) can be brought to bear on a problem. While nature doesn’t care about generating or maintaining organized complexity, humans can at least recognize a ‘problem’ or a shortcoming in the natural means that may be addressed by alternative solutions. Nature doesn’t have to worry about it, but we can. We have a stake in being alive.
Nevertheless. It is easy to see that life and evolution has depended on death and extinction. That IS how organized complexity in matter has emerged naturally. A thermodynamic opportunity (survival of a given complex configuration) presents itself in the ‘systematic rejection’ of faulty parts or in throwing out the trash. A potential niche becomes vacant. It tends to get filled. Recycling the broken bits in the form of useful raw material for the support of existing living systems enters into the scheme, to be sure. But it takes effort to segregate the signal from the noise, and however one cuts it (what’s essential from what’s not in terms of order) under the dispassionate glare of entropy, ‘death’ by any other name will remain a fact of life.
Anchor,
Thanks for the response. I agree that natural selection is how organized complexity in matter has emerged naturally. Not sure that bringing the ultimate arbiter entropy into the picture is meaningful in any practical sense. As for me, I’m only looking for a little progress in the very near future. 😉
“Not sure that bringing the ultimate arbiter entropy into the picture is meaningful in any practical sense.”
No “practical” sense implied in the meaning, I assure you. 😉
Just saying that whatever we may do to mitigate aging or delay death, our solutions will inevitably have to comply with natural laws, and that circumstance must continue to satisfy the appetite of entropy. If there is any meaning to be had at all, I submit it is there.
I am beginning to see an interesting convergence between biology and physics. A prediction can be made that the zeitgeist of the 21st century will be one where unusual sychronicities will begin appearing between biological processes and physics processes. Certainly this process of organism regeneration may have interesting correlations with a so called “bouncing universe”. I’m not thinking so much about the means, proteasomes, as with an overarching structure of death, regeneration, and recycling of an existing universe into a new baby universe. (Not at all thinking multiverses here. Hate the concept.)
For instance one could think of differentiation of cellular structure through stem cells as similar to differentiation of fields, forces, dimensions, and ultimately particles through asymptotic freedom in the early condensed state of the universe. Gradually these are pared away as the organism grows. Internal dependencies between biological structures then start manifesting themselves just as internal dependencies in solid-state physics manifests themselves as the universe cools and expands. At some very late stage in the development of the organism or universe everything will have become interdependent and there will be no excess material remaining for regeneration and the organism and the universe collapse, or bounce, into something new. ( and hopefully improved). 🙂
“Nature wants all the individual animal organisms to die, making room for new generations…”
Lets be a little more scientific here. Nature doesn’t care. Natural Selection also doesn’t care about extending your life (beyond a certain point) because you are probably already dead from a predator (by a certain point) so there is not much gain in fitness for extending your life past that point.
Comments above that suggest that there is “selection for” death should provide a reference. It is certainly not “easy to see” or the mainstream viewpoint of those that study evolution.
Really great post that, Nullius in Verba, thanks!
“Comments above that suggest that there is “selection for” death…”
Where is this suggestion?
“It is certainly not “easy to see” or the mainstream viewpoint of those that study evolution.”
Considering that the suggestion doesn’t exist and a false context is placed in its stead, its even easier to see how some people seem to prefer to make things up rather than read carefully.
As I understand it, cancer has been one of the monsters stalking efforts at extending life.
@2. David H.,
So all we have to do then, is to continue making babies beyond the usual biological timeframes? In fact indefinitely!
😉
Of course even it works, we are then faced with the problem of what to do with all those babies. In a world where their ancestors are not going to their, er, greater reward?
Soylent Green anyone?
🙁
So new cells in our bodies (the ones we’re making all the time) don’t get made using new proteins? Why not??
Heck, depending on how you decide who I am, I’ve been alive for three billion years or so, though I admit it gets pretty dicey passing through all those microscopic phases.
Of course there is selection for timely death, it’s due to limitation of resources and evolutionary arms race. Lifespan of all organisms is carefully tuned and linked to reproductive lifespan.
Due to natural selection each new generation is in general better adapted then the last one. It follows that once new generation is sexually mature it is better for it to take over the task of producing offspring from the last one (to ensure adaptation is as fast as possible). Keeping the old generation fertile for much longer would be counterproductive.
On the other hand keeping infertile individuals alive only makes sense if they can provide some benefit to the group which outweighs the cost of resources they consume, this may be for example helping with caring for the young and passing knowledge to them but eventually that job is also over (as new generation of elders comes along) and by that time they should die. If they were to keep on living they would imperil their own offspring.
Aging also serves its purpose – it is a great mechanism to ensure that in times of stress (limited resources, predators, etc) it is those old individuals who will die first, this prevents them from outcompeting the younger generations.
AI,
Your view seems to be based on two incorrect assumptions:
1. Humans may figure out the very complicated process of prolonging lifespans, but will not figure out to implement favorable adaptations, perhaps even better than through natural selection.
2. Humans living longer create mainly problems for society, imperiling offspring, using scarce resources and the like. Why isn’t the opposite the more likely outcome. What’s to stop it from happening? Not the laws of physics, but merely our current lack of understanding.
There’s repair at every level, molecular, cellular, tissue, system. DNA seems “stable” because there are active repair mechanisms at work all the time. Probably because the chemical structure of protein is so much more complex, and because no redundant copy of information about correct protein sequence exists outside of DNA, it’s a lot more feasible to simply destroy a protein and start from scratch than it is to repair it. This process happens all the time quite independently of aging. It’s an integral part of the cell’s many quality-control mechanisms, and even serves a very immediate regulatory roll. For instance, proteins that are no longer needed are actively targeted for destruction. Some proteins are even generated at a constitutive rate only to be chewed up on the proteasome within seconds so as to prime the cell for a hair-trigger response to specific stimuli, such as changes in the partial pressure of oxygen. Those cellular cleanup crews ARE active all the time. And by that I mean All. The. Time. Not a single protein gets synthesized without the proteasome standing in a sate of constant vigilance, ready to chew it to bits if it comes out wrong. All but the most quiescent of cells are constantly building proteins and breaking them down, and, again, this unremitting activity serves a variety of needs. If only anti-aging could be so easy.
I think there’s a LOT more to aging than old proteins hanging around. Steady loss of telomeric sequence and accumulated somatic mutations play a big roll in the degradation of correct protein synthesis and quality control as cells approach senescence. In very few cells and tissues is there no turnover. In fact, in most tissues, excepting very mitotically quiescent organs like the lens of the eye, the brain, the heart, there’s constant cellular turnover. That process requires constant remodeling of the extracellular matrix which virtually all cells outside of the circulatory system are in constant contact with. In fact, cells find it difficult to divide and migrate without burrowing through the protein matrix that they’re embedded in, and then having it be repaired in their wake.
All of this gets stuff gets creakier as we get older. It’s entropy, plain and simple, and it’s a ubiquitous problem. I hate to be a reflexive naysayer, but I find the notion that ramping up proteasomal activity would somehow reverse, or even slow, the aging process is way, way too optimistic.
So, I was being flippant with my earlier remark, I’m aware there’s still a lot of uncertainty regarding the role of aging. Nevertheless, I’m going to reiterate my skepticism for any theory of aging that claims it is an altruistic adaptation, adopted for the good of the species. Even the most ardent group-selectionist would raise an eyebrow at this claim. Keep in mind, evolution of altruistic traits is hard under any circumstance, and is constantly fighting against evolutionary pressure to be selfish. Could altruistic death evolve under some circumstances? Sure, and in fact, there are plenty of such cases. But aging is nearly universal among animals; for it to be altruistic, we’d need some kind of group selection operating on nearly every animal species on the planet. Take an example of extraordinarily successful altruism: multicellularity. Even here, selfish selection crops up routinely as cancer. And yet we don’t see methuseleh variants of organisms taking over and destroying entire species in the same way.
Nullius in Verba – Your model is interesting, I’ve never heard of it before, do you have any references? Infectious disease has been an important selection pressure on animals, and is probably critical to the evolution of sex, but I don’t see it being that useful a pressure to evolve aging, mainly for the reasons above.
AI – What you’re proposing is a classic example of group selection that just doesn’t work. Group selection only works when competition between groups overwhelms competition within groups. The advantage to an organism which cheated, and avoided dying to produce more offspring, or avoided dying off during famine would be tremendous, whereas the advantage to others provided by its dying would be spread over its children and every other organism in the population. A lot of this was covered a while ago, by GC Williams among others.
Everything points to this evolutionary truth: The fate of all multicellular organisms with proliferating cells is in either death by senescence or death by cancer. Natural selection insures it. All multicellular life has evolved to destroy cells that proliferate uncontrollably. If and when this check finally breaks down, cancer will claim the organism. Why? Because proliferating cells in the body evolve. Those that grow the fastest, furthest, and can gather resources the most successfully to those ends, will dominate. Hence, unless the whole organism goes down, cancer is an inevitability. The trick is to make the organism last long enough to reproduce before cancer or senescence claim it. All that is certain is that all multicellular life has adapted highly-conserved strategies to maintain this balance. In terms of the individual, nothing else matters from a reproductive and evolutionary standpoint.
So the fact that some organisms can live well past their reproductive stage is a bit of a mystery. Benefits conferred to younger generations is one plausible explanation, but far from iron-clad.