13 ms·

What Is Aging? Most Scientists Still Get It Wrong

197 points by sjcsjc 12y ago

unseraphim 12y ago
Excellent article. Not meant to be rigorous; only to give the broad stokes of a perspective that many have failed to grasp. Ever since I worked with embryos undergoing apoptosis under the influence of thalidomide in the late 1960s-early 1970s, it has been clear to me that aging is a programmed mechanism created by natural selection. The cumulative-error hypothesis should have been discarded long ago.
ExpiredLink 12y ago
You need not be a scientist to understand aging.
Widdershin 12y ago
This is truly the most amazing time to be alive (so far). No matter what repercussions the destruction of aging might have, it awes me that we talk of dramatically extended life and the colonization of the stars not only as something feasible, but even possible within the next century.
- collyw 12y ago
  Scientifically I agree with you economically not. We still base our economics system on infinite growth, but that is clearly reaching its limits. People living longer is only going to compound the problems.
  - Widdershin 12y ago
    I couldn't agree with you more. We have a fundamental culture of constant growth. It is by definition unsustainable. My hope is that if we did manage to ward off death for a bit longer, we might transcend some of our flawed notions. Who knows? Maybe young humans are fools, and that's the problem.
    - femto 12y ago
      Alternatively, mortality might make us selfless and less prone to flawed notions, as death forces us to eventually pass the baton to the next generation. Does wisdom come from age, or from impending death?
    - marcus_holmes 12y ago
      I kinda take issue with the "infinite growth is unsustainable" notion. If 1 dollar = 1 natural resource then clearly, yes, growth is constrained. But it isn't. My example for this is clerical work. Banks (for example) used to employ vast rooms of clerks, who spent entire days performing simple, repetitive maths in double-entry ledgers to make sure the bank knew where all the money was. Now all of that is done by computers, and so cheaply that banks now offer massively increased services. More value, for less cost. That's growth. Given that this is HN and frequented by legions of hackers trying to find problems to solve that create real value (by reducing costs or improving services), then this is the last place I'd expect the "growth is limited" mantra to be trotted out.
      - furyofantares 12y ago
        Ultimately, growth is limited by physical constraints, given our current understanding of physics. But it seems extremely premature to be worrying about this much unless you believe a singularity is right around the corner. And even then the idea of the singularity implies to me that we have no ability to predict what will happen - perhaps there are still enormous leaps to be made in physics that make our assumptions unfounded, or perhaps a greatly increased understanding of ourselves will eliminate our desire to continue to pursue growth indefinitely.
      - collyw 12y ago
        Derivatives and complex financial products now mean that no one knows where the money is, and seems to be a big part of the financial crisis. Here in Europe the banks are offering almost no interest on savings as a result. Looks like the US is the same. >"Given that this is HN and frequented by legions of hackers trying to find problems to solve that create real value" Looking at the list of YCombinator funded startups on the front page (Reddit, Airbnb, Scribd), none of them seem to be tackling the big issues of climate change, pollution, seas being over-fished, deforestation, lack of physical resources for a growing population. Sure they increase efficiency in some small area, but I don't see any that even address environmental issues. You need to remember that the majority of the worlds population live on very little money, and don't have the comfy lifestyles that many of us in the west have.
  - IndianAstronaut 12y ago
    We are not even close to discovering the cure for aging, so worrying about how it will change society is very premature. Until we can get a C eelegans worm to live for years, we are not remotely close to stopping aging.
    - lars 12y ago
      I thought the entirety of the C. elegans 302 neuron neural network had been implemented in code. If we're able to implement accurate copies of them, we have effectively made them immortal. Scale this up to human brains, and we are immortal ourselves.
      - IndianAstronaut 12y ago
        I suppose in a way that is correct, but I was refeering to getting the actual animal to live for a long time.
      - deleted 12y ago
        [deleted]
      - collyw 12y ago
        You are making pretty big assumptions about neural networks and consciousness. When people are in a vegetative state after a bad accident, their brains are still functioning to some extent - but it hardly means they are living / conscious.
- givan 12y ago
  Unfortunately it's just talking, there is no real progress in either space exploration let alone colonization or aging, hygiene and antibiotics was and it's still is the only thing that prolonged life in the last century, we still have a long way in both directions.
  - Widdershin 12y ago
    At least it will probably be interesting either way.
  - sergiosgc 12y ago
    Not really. Life expectancy at birth has steadily climbed: https://en.wikipedia.org/wiki/Life_expectancy#mediaviewer/File:Life_Expectancy_at_Birth_by_Region_1950-2050.png https://en.wikipedia.org/wiki/Life_expectancy#mediaviewer/Fi... The effect continued past the large effects of hygiene, antibiotics and child vaccination. You may argue that the curve is clearly asymptotic, and that a maximum age genetic barrier is clearly visible. You can't argue, however, that there isn't real progress after antibiotics and hygiene. This type of barrier is typical of technological evolution. We do strain a technology until returns are minimal, and only then sidestep to the next level of evolution. Steam machines were mechanical wonders before the combustion engine. Valves were amazing right before the transistor made an entrance. Current "corrective medicine" will reach its peak right before "manipulative medicine" enters the fray.
    - ekianjo 12y ago
      > The effect continued past the large effects of hygiene, antibiotics and child vaccination. You may argue that the curve is clearly asymptotic, and that a maximum age genetic barrier is clearly visible. You can't argue, however, that there isn't real progress after antibiotics and hygiene. we are seeing a resurgence of bacteria resistant to antibiotics, though, and we have no new lines of antibiotics to fight them. These advances may only be temporary.
      - venomsnake 12y ago
        > we are seeing a resurgence of bacteria resistant to antibiotics, though, and we have no new lines of antibiotics to fight them. These advances may only be temporary. We don't develop such, due to the broken way our pharmacy research is done. It makes no sense for pharma companies to develop antibiotics due to low ROI and lifetime of the product. A better approach for this is government to fund researchers for areas that private sector has abandoned.
- onion2k 12y ago
  This is truly the most amazing time to be alive (so far). If you're in the group of people privileged to have access to those innovations, yes. For everyone else it kind of sucks seeing what the elite get to play with.
  - Strom 12y ago
    From what I've observed, a great number of people who don't yet directly have access to new innovations aren't jealous, but are excited about the prospect of these innovations eventually getting wider application.
Htsthbjig 12y ago
It is important to note that the fact "Starvation is also a way to live longer." is probably wrong as some scientist have noticed. The problem is that animals in laboratories are "coach potatoes". They don't do the exercise they naturally do in their habitat searching for food. They live overcrowded in small cages and overstressed. Most lab animals are already ill from their artificial habitat, they have diabetes and other disorders. Strong social animals are isolated so they don't create problems like fighting each other(what are thy going to do if not?). Imagine you were forced to live in a sofa, or in your bed, all your life, with no sunlight but LED lighting. Most of those animals are overeating for their activity, so making them starve is better than not doing it. But this tells us nothing about real animals in the real world. http://www.vivisectioninformation.com/index.php?p=1_27_Unreproducable-results-from-the-animal-lab http://www.vivisectioninformation.com/index.php?p=1_27_Unrep...
- danieltillett 12y ago
  This is true, but either fortunately or unfortunately humans seem to be resembling lab animals more than wild animals.
  - irremediable 12y ago
    Is your claim as true for people who care about their health? The kind of person who has the dedication to do intermittent fasting probably has the dedication to do a fair amount of exercise.
    - danieltillett 12y ago
      My response was a bit of a throwaway pointing out that humans and lab animinals have rather converged in our lifestyles. What is more of a problem is the observation that human ageing has slowed rather dramatically in an evolutionary short time. The concern is that we have evolved this slower ageing physiology via a few simple adaptions (the low hanging fruit) and these are not reflected in the animal models. The fear is that when we use animal models the interventions we find in them will not apply to humans because we are already utilising these strategies naturally. For example, the level of Uric acid in humans is very high, so high that it tends to precipitate out in the extremities causing gout. One theory of why we have such high levels of Uric acid in our bloodstream is because it is protecting us from age related damage - it is one of the simple 'hacks' that we use to age slowly. Getting to your question there is some concern that calorie restriction won't work in humans for the same reason - we are already using the same pathways activated by calorie restriction in lab animals.
amelius 12y ago
I wonder what are the currently best established DIY techniques to slow aging. I know low food intake could help, but what else?
- sanxiyn 12y ago
  There is nothing else. Basically, calorie restriction works, and nothing else does. I recommend Fight Aging! if you are interested. https://www.fightaging.org/faq/ https://www.fightaging.org/faq/
  - Madmallard 12y ago
    I'm not so sure those are the only two. I'm fairly certain high dietary intake of various vegetables, fruits, and legumes over processed foods would probably greatly add to the life expectancy of regular people. Don't have a lot of hard evidence but I have relatives who outlived their brothers and sisters by 10-20 years because they just ate significantly healthier and moved around more.
    - sanxiyn 12y ago
      Healthy diet keeps you healthy, but it does not slow aging. It prevents death from reasons other than aging. To prove "slowing aging", you need to demonstrate increase in maximum lifespan, not average lifespan. Exercise, diet, etc. increase average lifespan. There is no evidence they increase maximum lifespan, none at all.
    - codexjourneys 12y ago
      "Moving around more" actually does significantly lower your risk of death from cardiovascular events (at the very least). http://healthland.time.com/2013/12/19/how-many-steps-does-it-take-to-avoid-a-heart-attack-researchers-find-out/ http://healthland.time.com/2013/12/19/how-many-steps-does-it... Common sense, while harder to study in a lab than a new specific medicine XYZ, actually can serve us well in the messy real world.
  - nhstanley 12y ago
givan 12y ago
Aging is encoded in our DNA with a purpose, if we will be able to fully understand how DNA works me might be able to partially disable it but will we want to? maybe when we will reach that level of knowledge we will also have the wisdom to understand the implications.
- sanxiyn 12y ago
  Do you want to die? Of course we will want to. I am sure there will be lots of side effects, but almost anything beats dying.
  - perlgeek 12y ago
    > Do you want to die? IMHO this is the wrong question to ask. As long as you continue to age, and your body degrades, you'll eventually not object to dying any more, because living isn't much fun. The much more interesting question is: do you want to age beyond a certain point?
    - akurilin 12y ago
      Then, can we dramatically slow down the body's natural degradation mechanisms, or even better, start reversing a few of them? That'd be a very good question to answer.
    - tarpherder 12y ago
      Not aging implies that you won't age beyond a certain point, or do you mean something different? Also, the question you ask is relevant even today with regular aging, and it's already hotly debated looking at euthanasia. I'm guessing euthanasia will have to be legalized if we ever do find a "cure" for aging.
      - perlgeek 12y ago
        > Not aging implies that you won't age beyond a certain point, or do you mean something different? I mean that I don't want my 4 year old to stop ageing, please :-) So "stop ageing" is only good as long as we have some decent measure of control over it. (I feel like I'm really stating the obvious here, but I don't know the whole discussion well enough to know if I can assume that obvious stuff is well-understood...)
quonn 12y ago
"These compromises have been made up ad hoc to avoid the inference that aging evolved to benefit the community, not the individual." Isn't this just group selection again? Has this view become more accepted nowadays among biologists? There are very compelling arguments against it. Maybe a better way to phrase it would be to say that aging has evolved to benefit the offspring, which traditionally happened to make up a significant part of the community?
- facepalm 12y ago
  What arguments are there against it? I had assumed that evolution applies on all levels (and not only to organisms). and what about ants - their evolution would always be to benefit the community, I suppose?
  - Nevermark 12y ago
    Ants are often siblings of each other due to the high number of ants produced by a single queen, so "group selection" for ants is really just "offspring selection". Most cases where group/community selection appears to take place have been explained by individual selection. Similarly, most (if not all) cases of symbiotic and cooperative behavior between species have been explained by an evolution of selfish survival behavior of each species. In both cases cooperation is not being directly selected for, but occurs as a special case of individual/selfish selection.
    - facepalm 12y ago
      You mean groups are selected for because the group benefits the individual? Sure - but that seems to me to just be a point of view, not a refutation of group selection. For example (to clarify), would you say religions are subject to evolution?
  - tokenadult 12y ago
    Thank you for asking a follow-up question asking for more information. In general, most biologists are convinced that there is no need for "group selection" processes to explain any biological phenomenon, as individual selection alongside kin selection seem to do the job of explaining phenomena observed so far in evolution.[1] [1] http://whyevolutionistrue.wordpress.com/2012/06/24/the-demise-of-group-selection/ http://whyevolutionistrue.wordpress.com/2012/06/24/the-demis... http://whyevolutionistrue.wordpress.com/2013/02/27/another-case-of-individual-selection-trumping-group-selection/ http://whyevolutionistrue.wordpress.com/2013/02/27/another-c...
danieltillett 12y ago
Ageing like everything in biology is incredibly complex. About the only thing we know for sure is that everyone with a simple theory to explain ageing is wrong. Ageing is at least as complex as cancer, but has received 1000th the study. If we assume understanding of a field correlates with resources committed then ageing research is in the 1920s. If you read the scientific literature from 1920s on cancer you will find everyone had a theory and everyone was wrong.
reasonattlm 12y ago
Despite the fact that the principal, fundamental biochemical differences distinguishing old tissue from young tissue are a largely settled and defensible consensus these past twenty years [1], there are many theories of aging [2]. From the point of view of development of treatments for aging, the most important divide is between programmed aging theories (a loud minority) and the view of aging as accumulated damage (the majority). A simplistic way of looking at it is to say that in the programmed aging view epigenetic change causes damage, while in the aging as damage view the damage is a side-effect of the normal operation of metabolism and leads to epigenetic changes as a reaction. (This simplistic view obscures a lot of argument within programmed aging, just as there is a lot of argument within the aging as damage view. The author of this article has developed a novel evolutionary theory of programmed aging to compare and contrast with a range of others, such as the hyperfunction theory of aging). At the present time we are entering an age of genetics. Whether the research community thinks of aging as a program or not is very important from the point of view of which treatments they try to chase. If aging is programmed, we'd expect damage repair to be of limited utility. If aging is accumulated damage, we'd expect attempts to change epigenetic patterns and gene expression levels to be of limited utility. Strangely, despite the fact that most researchers think of aging as damage accumulation, the research community actually spends much more time on trying to catalog and alter epigenetic and gene expression changes - the path that clearly won't have any great impact on the underlying causes of aging in that model. So if you do support programmed aging you should be pretty happy with the way things are going. If you don't, you really shouldn't: the field is heading in the wrong direction, for bad reasons. i.e. that it is easier to raise funds for the study and alteration of epigenetics, or the Big Pharma style development of drugs to do the same, which is the very hard exploration of how to safely alter a massively complex system that is very poorly understood, while it is much harder to raise funds to aim at rejuvenation through repair of damage, as this latter is a comparatively new approach in medicine. So despite the fact that the majority of the field thinks that aging is damage, next to no groups work on damage repair. They are largely working on building a catalog of the precise way in which damage interacts with metabolism in great detail, a part of the ongoing process of producing a complete map of metabolism, a process that has only just started in the grand scheme of things: what we have today is just the sketch of an outline. But that list of forms of damage that cause aging? That's good and defensible and therapies could be built starting now, with a proposed ten year timeline to get to working prototypes in mice given $100m/yr funding. The whole and main point of the SENS strategies for aging is that we can skip over the need for full understanding of the detailed operation of metabolism and just fix the damage we know distinguishes old tissue from young tissue. This is the logical way to go if aging is thought to be damage. And yet it has taken a decade of advocacy to get even a small number of researchers in the field to support this approach. [3] Want to prove whether aging is programmed or not? Implement SENS therapies, a clear and very detailed research program with a billion dollar price tag (much less than has already been spent on investigating sirtuins and mTOR, efforts that have produced nothing but knowledge of metabolism, and none of the promised treatments to modestly slow aging in healthy individuals). If that produces actual rejuvenation in mice, then aging is damage accumulation. If it doesn't, then it is programmed. End of story, fastest way to the target, job done. [1]: http://sens.org/research/introduction-to-sens-research http://sens.org/research/introduction-to-sens-research [2]: http://www.senescence.info/aging_theories.html http://www.senescence.info/aging_theories.html [3]: http://sens.org/about/leadership/research-advisory-board http://sens.org/about/leadership/research-advisory-board
teekert 12y ago
Oh how nice a couple of references to some peer reviewed articles would have been. Quotes like "This is my own perspective, shared by a handful of world-class aging scientists, but it is not yet mainstream." make all my scientific alarms go off. It is an interesting way of looking at it though.
- sorokod 12y ago
  "aging scientists"
- reasonattlm 12y ago
  Is it really so hard to run a PubMed search on someone with a distinctive name? http://www.ncbi.nlm.nih.gov/pubmed?term=Mitteldorf%20JJ%5BAuthor%20-%20Last%5D http://www.ncbi.nlm.nih.gov/pubmed?term=Mitteldorf%20JJ%5BAu... Biochemistry (Mosc) is a hotbed of programmed aging theory, and much of the theorizing in this area is generated by the Russian gerontology community.
- hnnewguy 12y ago
  >all my scientific alarms go off Is it required on HN that every article be terse list of peer-reviewed facts?
  - jacquesm 12y ago
    No, but when you make claims like those in the title then those peer-reviewed facts make all the difference. There's a ton of pseudo science and outright bs in the anti-aging scene so some references would definitely help in this case. Articles that don't make grandiose claims don't need to put their evidence up front. For 'most scientists' in the title read 'most scientists that hold a view contrary to that of the author'.
  - anoonmoose 12y ago
    Some days it just feels like every "scientific" article posted to HN is just someone's opinion with no data, and the only reason they even get upvoted is because people who probably didn't even read the article wanted to argue about it.
netforay 12y ago
To be Immortal, or not to be, that is the question for each cell. Here is simple explanation of Aging(and probably cure) https://www.authorea.com/users/13335/articles/13690/_show_article https://www.authorea.com/users/13335/articles/13690/_show_ar... This is a result of more than year of research by the Author.
jamesfisher 12y ago
> It is the body shutting itself down, putting itself out of the way after it has done its job, finished reproduction. Males' reproductive abilities continue into much later life. Wouldn't this theory then suggest that males would live longer? The opposite is in fact the case.
sorokod 12y ago
Can't take seriously an article with this kind of anthropomorphic attitude to biology
ekianjo 12y ago
This article gets so many things wrong I dont know where to start. The argument that "our bodies are useless after reproduction therefore aging makes us die when we are done" is so flawed in itself. If that was even remotely true, women would die much earlier than men since their bodies' reproductive age stops way earlier. So what is in nature's interest to have women live in their 80s versus men die in their 70s ? There is just no good "purpose" to justify those difference which are anyway way beyond the best times for reproductive ages for both genders.
- reasonattlm 12y ago
  In answer to your questions: The grandmother hypothesis: https://en.wikipedia.org/wiki/Grandmother_hypothesis https://en.wikipedia.org/wiki/Grandmother_hypothesis Evolution of sexually dimorphic longevity in humans: http://www.impactaging.com/papers/v6/n2/full/100640.html http://www.impactaging.com/papers/v6/n2/full/100640.html
  - ealloc 12y ago
    I like another theory I read recently: That it's because women's mitochondria are more fine-tuned to their nuclear genome: "The inheritance of mitochondria is asymmetric: you only get them from your mother, and your father makes no mitochondrial contribution at all. Your father’s mitochondrial contribution dies with him and is not passed on. What does that mean? It means that there can be no selection to fine tune mitochondria to the male nuclear genome." Mitochondria are extrmely important to the cell and have been linked to many effects of aging. The reasoning above suggests that mitochondria work more poorly in males. And indeed, the paper (linked below) explains that in fruit flies, mitochondrial genes in males are expressed with much higher variability than females. Your two links depend on human biology, but early male death is a much more general phenomenon. Males die earlier in the vast majority of animals (with gender). This idea could explain it. http://scienceblogs.com/pharyngula/2013/02/06/mothers-curse/ http://scienceblogs.com/pharyngula/2013/02/06/mothers-curse/ http://www.ncbi.nlm.nih.gov/pubmed/23281153 http://www.ncbi.nlm.nih.gov/pubmed/23281153
dschiptsov 12y ago
This "hard-wired cease of regeneration/renew" is a nice high-level theory, while attempts to find a single cause (or a single gene) to stop or reverse the process, is, probably, waste of time. There is no single process to be stopped, leave alone reversed. Each major subsystem (if not each major cell type) probably has its own "enough markers". That's why there are so many different causes of "natural" death.
- uniformlyrandom 12y ago
  Well, it is possible that every subsystem has its own self-destruction procedures, but that would be such an inefficient way to design a system. And nature is usually a very efficient designer.
  - edanm 12y ago
    "And nature is usually a very efficient designer." In what sense? For most senses of the word efficient, I think I'd disagree with that.
  - dschiptsov 12y ago
    It is not self-destruction, I think, it is rather "never evolved/selected for a long run". Everything "important" is supposed to happen in youth, at peak and then "doesn't matter". It is rather "stopping investing in repair" rather than "intentional self-destruction". But I think there is no single "marker/indicator" for this. So, they could keep regeneration of some specific kind of cells in a lab animal, by manipulating some hormone, but it doesn't affect the other parallel processes in different kinds of cells.
breck 12y ago
I enjoyed the post. Have one thing to add. IIRC the role of telomeres in aging has been known for twenty or thirty years. I'm blanking on the name, but there was a biotech company that went public in the 90's that had a drug in the works to lengthen or prevent the shortening of telomeres. But two decades later they haven't made much progress.
throwaway786534 12y ago
Aging isn't just one thing. It's not just the telomeres, or the hormonal changes. There's also the accumulated DNA damage which leads to cancer. And there are the evolutionary compromises, which was mentioned briefly at the end. One notable example of this is how children learn some things faster than adults. The brain shuts down expression of certain genes after childhood, and it's known that drugs like valproate can reverse this effect. Why did evolution make this tradeoff? Because all that extra brain activity requires more sleep, and that would leave us with fewer working hours. That was a useful tradeoff a century ago, but maybe not for some people today.
gabriel34 12y ago
The best explanation I found was on the book The Value of Tomorrow by Eduardo Giannetti, Brazilian philosopher and economist (in this chapter he had several consultants): If there is a trade-off between longer lifespan and reproductive capacity at a young age, there will also be a point of equilibrium. Suppose there was no senescence, we all lived perfectly healthy and at peak capacity for the duration of our lives. We would still have limited lifespan in nature, because of diseases, natural predators, etc. There would be a life expectancy, since people would not live forever. Now suppose a mutation occurs that grants the individual a boost in body functions at a young age with a caveat: a gradual decline in body functions after a certain age. If this certain age is way past the life expectancy of the population, this mutation would give competitive advantage to its bearers, with no real downside, since nobody lives way past the life expectancy anyway. This mutation would spread throughout the entire population and aging would establish itself in this population. The point of equilibrium in these trade-offs would be different for each population, since the environments and species are different, hence why hummingbirds, dogs, humans and turtles have wildly varying life expectancies. Trying to stop aging would involve stopping or mitigating these mechanisms, which are deeply ingrained in our systems. The consequences of doing so are far from straightforward, both to the individual (if we could not stop side effects to have the cake and eat it too) and to the population as a whole.
- UhUhUhUh 12y ago
  Yup. And the trade off between reproduction and aging is extremely well documented in biology. In short, reproduction prioritizes the set over the element. Kinda Borg-ish but that's what we have so far.
  - mitteldorf 12y ago
    The tradeoff between reproduction and aging is sometimes present and sometimes absent. The successes are over-reported and the failures under-reported, so you might get the impression of "extremely well documented" with a cursory reading. Here is an example from Cynthia Kenyon's lab, "Healthy Animals with Extreme Longevity" http://www.sciencemag.org/content/302/5645/611.full http://www.sciencemag.org/content/302/5645/611.full
jostmey 12y ago
My favorite explanation of Againg comes from William Hamilton. He took advantage of the Euler-Lotka equation to calculate the number of offspring that would be alive at any given point in the future. Using this equation from the field of demographics, he showed that senescence has only a marginal effect on fitness. As such, selective pressure would not be strong enough to filter out mutations that might result in aging. Finally, he was able to derive various mortality curves that "seem" to match pretty well with real living systems.
- mitteldorf 12y ago
  Marginal effect on INDIVIDUAL fitness, but a huge effect on THE FITNESS OF ECOSYSTEMS. Without aging, ecosystems would be unstable dynamic systems, and would not last more than a single generation. Without aging, everyone would die at once, in famines and natural disasters. Aging is necessary to spread out the death rate, so that populations don't swing wildly up and down.
jrh555 12y ago
One idea that I'm surprised I've never seen mentioned is the possibility that life ages in the same way that companies do. New high growth companies often have lots of money to hire new people, buy new equipment, build new office buildings, etc. When revenue eventually levels off or drops, often there are no longer enough resources to support everything that was built up in the growth phase. In older companies you might see a lot of old worn out equipment and infrastructure that is not getting repaired due to lack of resources. This effect can be seen on a larger scale in cities or even nations that experience a slowdown in growth. What if aging is simply a side effect of the fact that we stop growing at a certain age? It could be that certain key resources needed to fully repair the body are reduced or shut off once growth stops. Aging might even be a kind of negative growth. It's interesting that the effects of aging don't start showing up until after we stop growing. Also, the rate at which different forms of life age seems to be related to the growth rate. Some types of turtle can live to be over 200 years old but take 50 years to grow to full size. I'd be curious to see if there is any research into aging along these lines. If aging is related to growth, perhaps an anti-aging treatment could be as simple as finding a way to restart growth for short periods of time to generate the additional resources needed to repair damaged tissue. I have heard of human growth hormone being used as an anti-aging treatment though something tells me there would be more involved than just one hormone.
- xaa 12y ago
  Well, if the problem were "not enough resources", then you would expect that calories consumed would positively correlate with lifespan. But of course, calorie restriction increases lifespan. This theory was rather popular before 1950 and part of why people found calorie restriction's success surprising. A more modern and sophisticated version is called the "disposable soma" theory of aging, which states that reproduction competes with maintenance activities for the body's resources. But it too suffers from the same problem, and the additional problem that some organisms do not appreciably age. Yes, you are right that lifespan correlates with body mass/volume among species quite nicely, with some exceptions. And it is indeed quite suspicious that aging begins just about the same time growth stops. Growth hormone (GH) levels drop with age and GH supplementation can slow some age-related phenotypes. But, on the other hand, GH-deficient mice have increased lifespan, and GH is induced by cancer and its supplementation may increase cancer risk. There is a similar story for other growth hormones like IGF-1. Of course, these hormones, especially IGF-1, are intimately connected with metabolism, which is probably the set of pathways most heavily implicated in aging. So I am not sure this "coincidence" of aging starting when growth stops has a known explanation. It would however make an intriguing sci-fi novel if the "cure" for aging involved always growing larger and larger in size.
aetherson 12y ago
Does anyone here have the background to address this author's claims about telomeres? It seems like if telomeres were really a silver bullet to stop cellular aging, we'd have huge scientific consensus about it right now. My impression was that it was a promising line of investigation 20 years ago that didn't have the dramatic results that were hoped for. But I'm not in biology or medicine, and I may be wildly off base. I'm naturally cynical about the presence of a silver bullet for aging, though.
- xaa 12y ago
  The most convincing piece of evidence that telomeres are important in aging is that lack of telomerase (the protein that extends telomeres) or otherwise shortened telomeres causes progeroid (premature aging) disorders. But there are problems. First, telomerase is activated in many cancers to allow cancer cells to divide indefinitely, so there is a fear that adding telomerase as an anti-aging treatment would increase cancer risk. It is assumed that the finite length and existence of telomeres is an anti-cancer mechanism by cells. Secondly and even more problematic, aging occurs in tissues, and aging-like gene expression signatures in cells, which still have ample telomeres. There is a lot of evidence that other things like inflammation and metabolism, which have no direct connection to telomeres, are critical to aging. So telomerase/telomere lengthening is exceedingly unlikely to be a "silver bullet" for aging. Experiments show that it can extend lifespan in mice modestly. Conversely, though, upregulating or downregulating many other proteins which have nothing to do with telomeres can also increase lifespan. It is possible that telomeres are important in stem cell maintenance, since stem cells have to last a long time and replicate repeatedly (stem cells themselves are a very hot topic in aging right now).
Houshalter 12y ago
I was extremely skeptical of the title, but he makes a good case. Still it's very unlikely aging is evolved. An animal that lives longer would be able to reproduce more, therefore there is selection pressure for longer (reproductive) life spans. It's far more likely there are other reasons. For example limited telomeres prevent cells from multiplying out of control. And if aging was easy to biologically prevent/reverse, we would expect to find a few people out of billions that live far outside the normal life expectancy. Like someone with a rare combination of genes that happens to have longer telomeres or younger hormones etc. Instead everyone dies pretty consistently within 90 years, give or take a decade.
- rwissmann 12y ago
  "therefore there is selection pressure for longer (reproductive) life spans" this is too simplistic. there is also selection pressure for shorter generational cycles, leading to faster evolution. keeping older generations around would consume extra resources.
  - Houshalter 12y ago
    You are anthropomorphising evolution. Natural selection only favors individuals, not the species as a whole. Plus it's not clear if that would actually be a benefit. An organism which has survived and reproduced for hundreds of years probably has very fit genes.

197 points by sjcsjc 12y ago

Excellent article. Not meant to be rigorous; only to give the broad stokes of a perspective that many have failed to grasp. Ever since I worked with embryos undergoing apoptosis under the influence of thalidomide in the late 1960s-early 1970s, it has been clear to me that aging is a programmed mechanism created by natural selection. The cumulative-error hypothesis should have been discarded long ago.

ExpiredLink 12y ago

You need not be a scientist to understand aging.

Widdershin 12y ago

This is truly the most amazing time to be alive (so far). No matter what repercussions the destruction of aging might have, it awes me that we talk of dramatically extended life and the colonization of the stars not only as something feasible, but even possible within the next century.

collyw 12y ago
Scientifically I agree with you economically not. We still base our economics system on infinite growth, but that is clearly reaching its limits. People living longer is only going to compound the problems.
- Widdershin 12y ago
  I couldn't agree with you more. We have a fundamental culture of constant growth. It is by definition unsustainable. My hope is that if we did manage to ward off death for a bit longer, we might transcend some of our flawed notions. Who knows? Maybe young humans are fools, and that's the problem.
  - femto 12y ago
    Alternatively, mortality might make us selfless and less prone to flawed notions, as death forces us to eventually pass the baton to the next generation. Does wisdom come from age, or from impending death?
  - marcus_holmes 12y ago
    I kinda take issue with the "infinite growth is unsustainable" notion. If 1 dollar = 1 natural resource then clearly, yes, growth is constrained. But it isn't. My example for this is clerical work. Banks (for example) used to employ vast rooms of clerks, who spent entire days performing simple, repetitive maths in double-entry ledgers to make sure the bank knew where all the money was. Now all of that is done by computers, and so cheaply that banks now offer massively increased services. More value, for less cost. That's growth. Given that this is HN and frequented by legions of hackers trying to find problems to solve that create real value (by reducing costs or improving services), then this is the last place I'd expect the "growth is limited" mantra to be trotted out.
    - furyofantares 12y ago
      Ultimately, growth is limited by physical constraints, given our current understanding of physics. But it seems extremely premature to be worrying about this much unless you believe a singularity is right around the corner. And even then the idea of the singularity implies to me that we have no ability to predict what will happen - perhaps there are still enormous leaps to be made in physics that make our assumptions unfounded, or perhaps a greatly increased understanding of ourselves will eliminate our desire to continue to pursue growth indefinitely.
    - collyw 12y ago
      Derivatives and complex financial products now mean that no one knows where the money is, and seems to be a big part of the financial crisis. Here in Europe the banks are offering almost no interest on savings as a result. Looks like the US is the same. >"Given that this is HN and frequented by legions of hackers trying to find problems to solve that create real value" Looking at the list of YCombinator funded startups on the front page (Reddit, Airbnb, Scribd), none of them seem to be tackling the big issues of climate change, pollution, seas being over-fished, deforestation, lack of physical resources for a growing population. Sure they increase efficiency in some small area, but I don't see any that even address environmental issues. You need to remember that the majority of the worlds population live on very little money, and don't have the comfy lifestyles that many of us in the west have.
- IndianAstronaut 12y ago
  We are not even close to discovering the cure for aging, so worrying about how it will change society is very premature. Until we can get a C eelegans worm to live for years, we are not remotely close to stopping aging.
  - lars 12y ago
    I thought the entirety of the C. elegans 302 neuron neural network had been implemented in code. If we're able to implement accurate copies of them, we have effectively made them immortal. Scale this up to human brains, and we are immortal ourselves.
    - IndianAstronaut 12y ago
      I suppose in a way that is correct, but I was refeering to getting the actual animal to live for a long time.
    - deleted 12y ago
      [deleted]
    - collyw 12y ago
      You are making pretty big assumptions about neural networks and consciousness. When people are in a vegetative state after a bad accident, their brains are still functioning to some extent - but it hardly means they are living / conscious.
givan 12y ago
Unfortunately it's just talking, there is no real progress in either space exploration let alone colonization or aging, hygiene and antibiotics was and it's still is the only thing that prolonged life in the last century, we still have a long way in both directions.
- Widdershin 12y ago
  At least it will probably be interesting either way.
- sergiosgc 12y ago
  Not really. Life expectancy at birth has steadily climbed: https://en.wikipedia.org/wiki/Life_expectancy#mediaviewer/File:Life_Expectancy_at_Birth_by_Region_1950-2050.png https://en.wikipedia.org/wiki/Life_expectancy#mediaviewer/Fi... The effect continued past the large effects of hygiene, antibiotics and child vaccination. You may argue that the curve is clearly asymptotic, and that a maximum age genetic barrier is clearly visible. You can't argue, however, that there isn't real progress after antibiotics and hygiene. This type of barrier is typical of technological evolution. We do strain a technology until returns are minimal, and only then sidestep to the next level of evolution. Steam machines were mechanical wonders before the combustion engine. Valves were amazing right before the transistor made an entrance. Current "corrective medicine" will reach its peak right before "manipulative medicine" enters the fray.
  - ekianjo 12y ago
    > The effect continued past the large effects of hygiene, antibiotics and child vaccination. You may argue that the curve is clearly asymptotic, and that a maximum age genetic barrier is clearly visible. You can't argue, however, that there isn't real progress after antibiotics and hygiene. we are seeing a resurgence of bacteria resistant to antibiotics, though, and we have no new lines of antibiotics to fight them. These advances may only be temporary.
    - venomsnake 12y ago
      > we are seeing a resurgence of bacteria resistant to antibiotics, though, and we have no new lines of antibiotics to fight them. These advances may only be temporary. We don't develop such, due to the broken way our pharmacy research is done. It makes no sense for pharma companies to develop antibiotics due to low ROI and lifetime of the product. A better approach for this is government to fund researchers for areas that private sector has abandoned.
onion2k 12y ago
This is truly the most amazing time to be alive (so far). If you're in the group of people privileged to have access to those innovations, yes. For everyone else it kind of sucks seeing what the elite get to play with.
- Strom 12y ago
  From what I've observed, a great number of people who don't yet directly have access to new innovations aren't jealous, but are excited about the prospect of these innovations eventually getting wider application.

Htsthbjig 12y ago

It is important to note that the fact "Starvation is also a way to live longer." is probably wrong as some scientist have noticed. The problem is that animals in laboratories are "coach potatoes". They don't do the exercise they naturally do in their habitat searching for food. They live overcrowded in small cages and overstressed. Most lab animals are already ill from their artificial habitat, they have diabetes and other disorders. Strong social animals are isolated so they don't create problems like fighting each other(what are thy going to do if not?). Imagine you were forced to live in a sofa, or in your bed, all your life, with no sunlight but LED lighting. Most of those animals are overeating for their activity, so making them starve is better than not doing it. But this tells us nothing about real animals in the real world. http://www.vivisectioninformation.com/index.php?p=1_27_Unreproducable-results-from-the-animal-lab http://www.vivisectioninformation.com/index.php?p=1_27_Unrep...

danieltillett 12y ago
This is true, but either fortunately or unfortunately humans seem to be resembling lab animals more than wild animals.
- irremediable 12y ago
  Is your claim as true for people who care about their health? The kind of person who has the dedication to do intermittent fasting probably has the dedication to do a fair amount of exercise.
  - danieltillett 12y ago
    My response was a bit of a throwaway pointing out that humans and lab animinals have rather converged in our lifestyles. What is more of a problem is the observation that human ageing has slowed rather dramatically in an evolutionary short time. The concern is that we have evolved this slower ageing physiology via a few simple adaptions (the low hanging fruit) and these are not reflected in the animal models. The fear is that when we use animal models the interventions we find in them will not apply to humans because we are already utilising these strategies naturally. For example, the level of Uric acid in humans is very high, so high that it tends to precipitate out in the extremities causing gout. One theory of why we have such high levels of Uric acid in our bloodstream is because it is protecting us from age related damage - it is one of the simple 'hacks' that we use to age slowly. Getting to your question there is some concern that calorie restriction won't work in humans for the same reason - we are already using the same pathways activated by calorie restriction in lab animals.

amelius 12y ago

I wonder what are the currently best established DIY techniques to slow aging. I know low food intake could help, but what else?

sanxiyn 12y ago
There is nothing else. Basically, calorie restriction works, and nothing else does. I recommend Fight Aging! if you are interested. https://www.fightaging.org/faq/ https://www.fightaging.org/faq/
- Madmallard 12y ago
  I'm not so sure those are the only two. I'm fairly certain high dietary intake of various vegetables, fruits, and legumes over processed foods would probably greatly add to the life expectancy of regular people. Don't have a lot of hard evidence but I have relatives who outlived their brothers and sisters by 10-20 years because they just ate significantly healthier and moved around more.
  - sanxiyn 12y ago
    Healthy diet keeps you healthy, but it does not slow aging. It prevents death from reasons other than aging. To prove "slowing aging", you need to demonstrate increase in maximum lifespan, not average lifespan. Exercise, diet, etc. increase average lifespan. There is no evidence they increase maximum lifespan, none at all.
  - codexjourneys 12y ago
    "Moving around more" actually does significantly lower your risk of death from cardiovascular events (at the very least). http://healthland.time.com/2013/12/19/how-many-steps-does-it-take-to-avoid-a-heart-attack-researchers-find-out/ http://healthland.time.com/2013/12/19/how-many-steps-does-it... Common sense, while harder to study in a lab than a new specific medicine XYZ, actually can serve us well in the messy real world.
- nhstanley 12y ago

givan 12y ago

Aging is encoded in our DNA with a purpose, if we will be able to fully understand how DNA works me might be able to partially disable it but will we want to? maybe when we will reach that level of knowledge we will also have the wisdom to understand the implications.

sanxiyn 12y ago
Do you want to die? Of course we will want to. I am sure there will be lots of side effects, but almost anything beats dying.
- perlgeek 12y ago
  > Do you want to die? IMHO this is the wrong question to ask. As long as you continue to age, and your body degrades, you'll eventually not object to dying any more, because living isn't much fun. The much more interesting question is: do you want to age beyond a certain point?
  - akurilin 12y ago
    Then, can we dramatically slow down the body's natural degradation mechanisms, or even better, start reversing a few of them? That'd be a very good question to answer.
  - tarpherder 12y ago
    Not aging implies that you won't age beyond a certain point, or do you mean something different? Also, the question you ask is relevant even today with regular aging, and it's already hotly debated looking at euthanasia. I'm guessing euthanasia will have to be legalized if we ever do find a "cure" for aging.
    - perlgeek 12y ago
      > Not aging implies that you won't age beyond a certain point, or do you mean something different? I mean that I don't want my 4 year old to stop ageing, please :-) So "stop ageing" is only good as long as we have some decent measure of control over it. (I feel like I'm really stating the obvious here, but I don't know the whole discussion well enough to know if I can assume that obvious stuff is well-understood...)

quonn 12y ago

"These compromises have been made up ad hoc to avoid the inference that aging evolved to benefit the community, not the individual." Isn't this just group selection again? Has this view become more accepted nowadays among biologists? There are very compelling arguments against it. Maybe a better way to phrase it would be to say that aging has evolved to benefit the offspring, which traditionally happened to make up a significant part of the community?

facepalm 12y ago
What arguments are there against it? I had assumed that evolution applies on all levels (and not only to organisms). and what about ants - their evolution would always be to benefit the community, I suppose?
- Nevermark 12y ago
  Ants are often siblings of each other due to the high number of ants produced by a single queen, so "group selection" for ants is really just "offspring selection". Most cases where group/community selection appears to take place have been explained by individual selection. Similarly, most (if not all) cases of symbiotic and cooperative behavior between species have been explained by an evolution of selfish survival behavior of each species. In both cases cooperation is not being directly selected for, but occurs as a special case of individual/selfish selection.
  - facepalm 12y ago
    You mean groups are selected for because the group benefits the individual? Sure - but that seems to me to just be a point of view, not a refutation of group selection. For example (to clarify), would you say religions are subject to evolution?
- tokenadult 12y ago
  Thank you for asking a follow-up question asking for more information. In general, most biologists are convinced that there is no need for "group selection" processes to explain any biological phenomenon, as individual selection alongside kin selection seem to do the job of explaining phenomena observed so far in evolution.[1] [1] http://whyevolutionistrue.wordpress.com/2012/06/24/the-demise-of-group-selection/ http://whyevolutionistrue.wordpress.com/2012/06/24/the-demis... http://whyevolutionistrue.wordpress.com/2013/02/27/another-case-of-individual-selection-trumping-group-selection/ http://whyevolutionistrue.wordpress.com/2013/02/27/another-c...

danieltillett 12y ago

Ageing like everything in biology is incredibly complex. About the only thing we know for sure is that everyone with a simple theory to explain ageing is wrong. Ageing is at least as complex as cancer, but has received 1000th the study. If we assume understanding of a field correlates with resources committed then ageing research is in the 1920s. If you read the scientific literature from 1920s on cancer you will find everyone had a theory and everyone was wrong.

reasonattlm 12y ago

Despite the fact that the principal, fundamental biochemical differences distinguishing old tissue from young tissue are a largely settled and defensible consensus these past twenty years [1], there are many theories of aging [2]. From the point of view of development of treatments for aging, the most important divide is between programmed aging theories (a loud minority) and the view of aging as accumulated damage (the majority). A simplistic way of looking at it is to say that in the programmed aging view epigenetic change causes damage, while in the aging as damage view the damage is a side-effect of the normal operation of metabolism and leads to epigenetic changes as a reaction. (This simplistic view obscures a lot of argument within programmed aging, just as there is a lot of argument within the aging as damage view. The author of this article has developed a novel evolutionary theory of programmed aging to compare and contrast with a range of others, such as the hyperfunction theory of aging). At the present time we are entering an age of genetics. Whether the research community thinks of aging as a program or not is very important from the point of view of which treatments they try to chase. If aging is programmed, we'd expect damage repair to be of limited utility. If aging is accumulated damage, we'd expect attempts to change epigenetic patterns and gene expression levels to be of limited utility. Strangely, despite the fact that most researchers think of aging as damage accumulation, the research community actually spends much more time on trying to catalog and alter epigenetic and gene expression changes - the path that clearly won't have any great impact on the underlying causes of aging in that model. So if you do support programmed aging you should be pretty happy with the way things are going. If you don't, you really shouldn't: the field is heading in the wrong direction, for bad reasons. i.e. that it is easier to raise funds for the study and alteration of epigenetics, or the Big Pharma style development of drugs to do the same, which is the very hard exploration of how to safely alter a massively complex system that is very poorly understood, while it is much harder to raise funds to aim at rejuvenation through repair of damage, as this latter is a comparatively new approach in medicine. So despite the fact that the majority of the field thinks that aging is damage, next to no groups work on damage repair. They are largely working on building a catalog of the precise way in which damage interacts with metabolism in great detail, a part of the ongoing process of producing a complete map of metabolism, a process that has only just started in the grand scheme of things: what we have today is just the sketch of an outline. But that list of forms of damage that cause aging? That's good and defensible and therapies could be built starting now, with a proposed ten year timeline to get to working prototypes in mice given $100m/yr funding. The whole and main point of the SENS strategies for aging is that we can skip over the need for full understanding of the detailed operation of metabolism and just fix the damage we know distinguishes old tissue from young tissue. This is the logical way to go if aging is thought to be damage. And yet it has taken a decade of advocacy to get even a small number of researchers in the field to support this approach. [3] Want to prove whether aging is programmed or not? Implement SENS therapies, a clear and very detailed research program with a billion dollar price tag (much less than has already been spent on investigating sirtuins and mTOR, efforts that have produced nothing but knowledge of metabolism, and none of the promised treatments to modestly slow aging in healthy individuals). If that produces actual rejuvenation in mice, then aging is damage accumulation. If it doesn't, then it is programmed. End of story, fastest way to the target, job done. [1]: http://sens.org/research/introduction-to-sens-research http://sens.org/research/introduction-to-sens-research [2]: http://www.senescence.info/aging_theories.html http://www.senescence.info/aging_theories.html [3]: http://sens.org/about/leadership/research-advisory-board http://sens.org/about/leadership/research-advisory-board

teekert 12y ago

Oh how nice a couple of references to some peer reviewed articles would have been. Quotes like "This is my own perspective, shared by a handful of world-class aging scientists, but it is not yet mainstream." make all my scientific alarms go off. It is an interesting way of looking at it though.

sorokod 12y ago
"aging scientists"
reasonattlm 12y ago
Is it really so hard to run a PubMed search on someone with a distinctive name? http://www.ncbi.nlm.nih.gov/pubmed?term=Mitteldorf%20JJ%5BAuthor%20-%20Last%5D http://www.ncbi.nlm.nih.gov/pubmed?term=Mitteldorf%20JJ%5BAu... Biochemistry (Mosc) is a hotbed of programmed aging theory, and much of the theorizing in this area is generated by the Russian gerontology community.
hnnewguy 12y ago
>all my scientific alarms go off Is it required on HN that every article be terse list of peer-reviewed facts?
- jacquesm 12y ago
  No, but when you make claims like those in the title then those peer-reviewed facts make all the difference. There's a ton of pseudo science and outright bs in the anti-aging scene so some references would definitely help in this case. Articles that don't make grandiose claims don't need to put their evidence up front. For 'most scientists' in the title read 'most scientists that hold a view contrary to that of the author'.
- anoonmoose 12y ago
  Some days it just feels like every "scientific" article posted to HN is just someone's opinion with no data, and the only reason they even get upvoted is because people who probably didn't even read the article wanted to argue about it.

netforay 12y ago

To be Immortal, or not to be, that is the question for each cell. Here is simple explanation of Aging(and probably cure) https://www.authorea.com/users/13335/articles/13690/_show_article https://www.authorea.com/users/13335/articles/13690/_show_ar... This is a result of more than year of research by the Author.

jamesfisher 12y ago

> It is the body shutting itself down, putting itself out of the way after it has done its job, finished reproduction. Males' reproductive abilities continue into much later life. Wouldn't this theory then suggest that males would live longer? The opposite is in fact the case.

sorokod 12y ago

Can't take seriously an article with this kind of anthropomorphic attitude to biology

ekianjo 12y ago

This article gets so many things wrong I dont know where to start. The argument that "our bodies are useless after reproduction therefore aging makes us die when we are done" is so flawed in itself. If that was even remotely true, women would die much earlier than men since their bodies' reproductive age stops way earlier. So what is in nature's interest to have women live in their 80s versus men die in their 70s ? There is just no good "purpose" to justify those difference which are anyway way beyond the best times for reproductive ages for both genders.

reasonattlm 12y ago
In answer to your questions: The grandmother hypothesis: https://en.wikipedia.org/wiki/Grandmother_hypothesis https://en.wikipedia.org/wiki/Grandmother_hypothesis Evolution of sexually dimorphic longevity in humans: http://www.impactaging.com/papers/v6/n2/full/100640.html http://www.impactaging.com/papers/v6/n2/full/100640.html
- ealloc 12y ago
  I like another theory I read recently: That it's because women's mitochondria are more fine-tuned to their nuclear genome: "The inheritance of mitochondria is asymmetric: you only get them from your mother, and your father makes no mitochondrial contribution at all. Your father’s mitochondrial contribution dies with him and is not passed on. What does that mean? It means that there can be no selection to fine tune mitochondria to the male nuclear genome." Mitochondria are extrmely important to the cell and have been linked to many effects of aging. The reasoning above suggests that mitochondria work more poorly in males. And indeed, the paper (linked below) explains that in fruit flies, mitochondrial genes in males are expressed with much higher variability than females. Your two links depend on human biology, but early male death is a much more general phenomenon. Males die earlier in the vast majority of animals (with gender). This idea could explain it. http://scienceblogs.com/pharyngula/2013/02/06/mothers-curse/ http://scienceblogs.com/pharyngula/2013/02/06/mothers-curse/ http://www.ncbi.nlm.nih.gov/pubmed/23281153 http://www.ncbi.nlm.nih.gov/pubmed/23281153

dschiptsov 12y ago

This "hard-wired cease of regeneration/renew" is a nice high-level theory, while attempts to find a single cause (or a single gene) to stop or reverse the process, is, probably, waste of time. There is no single process to be stopped, leave alone reversed. Each major subsystem (if not each major cell type) probably has its own "enough markers". That's why there are so many different causes of "natural" death.

uniformlyrandom 12y ago
Well, it is possible that every subsystem has its own self-destruction procedures, but that would be such an inefficient way to design a system. And nature is usually a very efficient designer.
- edanm 12y ago
  "And nature is usually a very efficient designer." In what sense? For most senses of the word efficient, I think I'd disagree with that.
- dschiptsov 12y ago
  It is not self-destruction, I think, it is rather "never evolved/selected for a long run". Everything "important" is supposed to happen in youth, at peak and then "doesn't matter". It is rather "stopping investing in repair" rather than "intentional self-destruction". But I think there is no single "marker/indicator" for this. So, they could keep regeneration of some specific kind of cells in a lab animal, by manipulating some hormone, but it doesn't affect the other parallel processes in different kinds of cells.

breck 12y ago

I enjoyed the post. Have one thing to add. IIRC the role of telomeres in aging has been known for twenty or thirty years. I'm blanking on the name, but there was a biotech company that went public in the 90's that had a drug in the works to lengthen or prevent the shortening of telomeres. But two decades later they haven't made much progress.

throwaway786534 12y ago

Aging isn't just one thing. It's not just the telomeres, or the hormonal changes. There's also the accumulated DNA damage which leads to cancer. And there are the evolutionary compromises, which was mentioned briefly at the end. One notable example of this is how children learn some things faster than adults. The brain shuts down expression of certain genes after childhood, and it's known that drugs like valproate can reverse this effect. Why did evolution make this tradeoff? Because all that extra brain activity requires more sleep, and that would leave us with fewer working hours. That was a useful tradeoff a century ago, but maybe not for some people today.

gabriel34 12y ago

The best explanation I found was on the book The Value of Tomorrow by Eduardo Giannetti, Brazilian philosopher and economist (in this chapter he had several consultants): If there is a trade-off between longer lifespan and reproductive capacity at a young age, there will also be a point of equilibrium. Suppose there was no senescence, we all lived perfectly healthy and at peak capacity for the duration of our lives. We would still have limited lifespan in nature, because of diseases, natural predators, etc. There would be a life expectancy, since people would not live forever. Now suppose a mutation occurs that grants the individual a boost in body functions at a young age with a caveat: a gradual decline in body functions after a certain age. If this certain age is way past the life expectancy of the population, this mutation would give competitive advantage to its bearers, with no real downside, since nobody lives way past the life expectancy anyway. This mutation would spread throughout the entire population and aging would establish itself in this population. The point of equilibrium in these trade-offs would be different for each population, since the environments and species are different, hence why hummingbirds, dogs, humans and turtles have wildly varying life expectancies. Trying to stop aging would involve stopping or mitigating these mechanisms, which are deeply ingrained in our systems. The consequences of doing so are far from straightforward, both to the individual (if we could not stop side effects to have the cake and eat it too) and to the population as a whole.

UhUhUhUh 12y ago
Yup. And the trade off between reproduction and aging is extremely well documented in biology. In short, reproduction prioritizes the set over the element. Kinda Borg-ish but that's what we have so far.
- mitteldorf 12y ago
  The tradeoff between reproduction and aging is sometimes present and sometimes absent. The successes are over-reported and the failures under-reported, so you might get the impression of "extremely well documented" with a cursory reading. Here is an example from Cynthia Kenyon's lab, "Healthy Animals with Extreme Longevity" http://www.sciencemag.org/content/302/5645/611.full http://www.sciencemag.org/content/302/5645/611.full

jostmey 12y ago

My favorite explanation of Againg comes from William Hamilton. He took advantage of the Euler-Lotka equation to calculate the number of offspring that would be alive at any given point in the future. Using this equation from the field of demographics, he showed that senescence has only a marginal effect on fitness. As such, selective pressure would not be strong enough to filter out mutations that might result in aging. Finally, he was able to derive various mortality curves that "seem" to match pretty well with real living systems.

mitteldorf 12y ago
Marginal effect on INDIVIDUAL fitness, but a huge effect on THE FITNESS OF ECOSYSTEMS. Without aging, ecosystems would be unstable dynamic systems, and would not last more than a single generation. Without aging, everyone would die at once, in famines and natural disasters. Aging is necessary to spread out the death rate, so that populations don't swing wildly up and down.

jrh555 12y ago

One idea that I'm surprised I've never seen mentioned is the possibility that life ages in the same way that companies do. New high growth companies often have lots of money to hire new people, buy new equipment, build new office buildings, etc. When revenue eventually levels off or drops, often there are no longer enough resources to support everything that was built up in the growth phase. In older companies you might see a lot of old worn out equipment and infrastructure that is not getting repaired due to lack of resources. This effect can be seen on a larger scale in cities or even nations that experience a slowdown in growth. What if aging is simply a side effect of the fact that we stop growing at a certain age? It could be that certain key resources needed to fully repair the body are reduced or shut off once growth stops. Aging might even be a kind of negative growth. It's interesting that the effects of aging don't start showing up until after we stop growing. Also, the rate at which different forms of life age seems to be related to the growth rate. Some types of turtle can live to be over 200 years old but take 50 years to grow to full size. I'd be curious to see if there is any research into aging along these lines. If aging is related to growth, perhaps an anti-aging treatment could be as simple as finding a way to restart growth for short periods of time to generate the additional resources needed to repair damaged tissue. I have heard of human growth hormone being used as an anti-aging treatment though something tells me there would be more involved than just one hormone.

xaa 12y ago
Well, if the problem were "not enough resources", then you would expect that calories consumed would positively correlate with lifespan. But of course, calorie restriction increases lifespan. This theory was rather popular before 1950 and part of why people found calorie restriction's success surprising. A more modern and sophisticated version is called the "disposable soma" theory of aging, which states that reproduction competes with maintenance activities for the body's resources. But it too suffers from the same problem, and the additional problem that some organisms do not appreciably age. Yes, you are right that lifespan correlates with body mass/volume among species quite nicely, with some exceptions. And it is indeed quite suspicious that aging begins just about the same time growth stops. Growth hormone (GH) levels drop with age and GH supplementation can slow some age-related phenotypes. But, on the other hand, GH-deficient mice have increased lifespan, and GH is induced by cancer and its supplementation may increase cancer risk. There is a similar story for other growth hormones like IGF-1. Of course, these hormones, especially IGF-1, are intimately connected with metabolism, which is probably the set of pathways most heavily implicated in aging. So I am not sure this "coincidence" of aging starting when growth stops has a known explanation. It would however make an intriguing sci-fi novel if the "cure" for aging involved always growing larger and larger in size.

aetherson 12y ago

Does anyone here have the background to address this author's claims about telomeres? It seems like if telomeres were really a silver bullet to stop cellular aging, we'd have huge scientific consensus about it right now. My impression was that it was a promising line of investigation 20 years ago that didn't have the dramatic results that were hoped for. But I'm not in biology or medicine, and I may be wildly off base. I'm naturally cynical about the presence of a silver bullet for aging, though.

xaa 12y ago
The most convincing piece of evidence that telomeres are important in aging is that lack of telomerase (the protein that extends telomeres) or otherwise shortened telomeres causes progeroid (premature aging) disorders. But there are problems. First, telomerase is activated in many cancers to allow cancer cells to divide indefinitely, so there is a fear that adding telomerase as an anti-aging treatment would increase cancer risk. It is assumed that the finite length and existence of telomeres is an anti-cancer mechanism by cells. Secondly and even more problematic, aging occurs in tissues, and aging-like gene expression signatures in cells, which still have ample telomeres. There is a lot of evidence that other things like inflammation and metabolism, which have no direct connection to telomeres, are critical to aging. So telomerase/telomere lengthening is exceedingly unlikely to be a "silver bullet" for aging. Experiments show that it can extend lifespan in mice modestly. Conversely, though, upregulating or downregulating many other proteins which have nothing to do with telomeres can also increase lifespan. It is possible that telomeres are important in stem cell maintenance, since stem cells have to last a long time and replicate repeatedly (stem cells themselves are a very hot topic in aging right now).

Houshalter 12y ago

I was extremely skeptical of the title, but he makes a good case. Still it's very unlikely aging is evolved. An animal that lives longer would be able to reproduce more, therefore there is selection pressure for longer (reproductive) life spans. It's far more likely there are other reasons. For example limited telomeres prevent cells from multiplying out of control. And if aging was easy to biologically prevent/reverse, we would expect to find a few people out of billions that live far outside the normal life expectancy. Like someone with a rare combination of genes that happens to have longer telomeres or younger hormones etc. Instead everyone dies pretty consistently within 90 years, give or take a decade.

rwissmann 12y ago
"therefore there is selection pressure for longer (reproductive) life spans" this is too simplistic. there is also selection pressure for shorter generational cycles, leading to faster evolution. keeping older generations around would consume extra resources.
- Houshalter 12y ago
  You are anthropomorphising evolution. Natural selection only favors individuals, not the species as a whole. Plus it's not clear if that would actually be a benefit. An organism which has survived and reproduced for hundreds of years probably has very fit genes.