What Is Aging? Most Scientists Still Get It Wrong | Hacker News Reader

What Is Aging? Most Scientists Still Get It Wrong

joshmitteldorf.scienceblog.com

197 pointssjcsjc130 comments

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_Unrep...

This is true, but either fortunately or unfortunately humans seem to be resembling lab animals more than wild animals.

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.

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.

Thanks for your detailed follow-up! My apologies for only reading it now. I was always a bit sceptical of the fasting experiments being representative of humans, but I'd never looked at the specifics of it.

If it means anything I think fasting may help in humans - not by slowing ageing directly, but by improving glucose control. I would expect an increase in average life expectancy from intermittent fasting while having little effect on maximum life expectancy.

I started intermittent fasting around a year ago, and usually I do do reasonable amount of exercise. I had a health review as part of my work three months after I started. I really wanted to stop, because the fasting was difficult (I was doing two days a week). While before I was fairly healthy, my blood pressure has always been a bit high, as with my cholesterol. After fasting they were both gone down to good levels.

Anyway I cut down to one day a week, which is far more manageable (I am pretty skinny, and I was struggling to keep my weight up). Now it feels good. I have a feeling it is to do with insulin sensitivity, as I no longer feel hunger pangs, and don't get the sleepy feeling after having a huge lunch.

So yes, I consider myself reasonably healthy, but even so I had blood pressure and cholesterol that were bordering between normal and high levels.

I'm strongly considering starting this. Any tips? (Feel free to email if you don't want to share publicly.)

First month is tough, getting gradually easier. Probably easier to have a few small snacks to make up your day, followed by a bulky low calorie meal in the evening (I used to go for a small chicken breast in a stir fry with minimal oil - protein feels more satisfying).

Now I kind of enjoy it (one day a week). I occasionally stop, i.e. on holiday, and I do notice a bit of lethargy creeping in a time to time.

Otherwise, just get a cookbook and go for recipes that are less than 600 calories (that's the total I allow my self on a fast day).

Should have the same health test in March, so hopefully one day a week is still doing well (I have a blood pressure monitor to check that and and mine still down, actually it improved when I went from 2 to 1 day a week, maybe because I was eating a lot of crap to try and keep my weight up).

Have a google about for BBC's Horizon "Eat fast live longer". I can't find a full length version on youtube just now, but I am sure it is somewhere on the web. That's what inspired me.

Thanks for the tips! Can you still work out on the fasting days or would that be ridiculous? Can you concentrate at work?

First few times is a bit tricky concentrating at work - actually I started feeling really high towards the end of the first evening. After two or three weeks its fine. Feels a bit more tired towards the end of the day - like you might after a long hike or something - pleasant tired, and want to go to bed an hour earlier than usual.

I personally avoid exercise on the fast days, but some people swear by it (reddit has some subs on keto diet, which I think is combining exercise fasting and diet), but I am probably in a minority that I am not trying to loose weight with it.

Actually in the afternoon / evening it feels a lot like you have been on a long hike or something similar - probably due to using up your blood glycogen. You likely wouldn't really want to go to the gym after that.

Did you normally get enough sleep before starting the fasting? You mention that you now get more sleep, and I wonder how much of a factor that is in improving your blood pressure and cholesterol.

Its only on the fasting days that I feel tired earlier, and sleep an hour more. (I used to get more sleep a couple of years ago, before I moved in with my GF - she wakes us up an hour earlier than I used).

The most important thing to keep in mind is that your own body is your best experimental lab, and that you should pay attention to what works FOR YOU and keep a diary. Other people's experience is good for giving you ideas of things to try, but people vary considerably, and you will find your own experience changes from week to week, as well as evolving over time.

IF is not necessarily calorie restriction, it's more caloric timing. You can use IF to optimize gaining lean weight (muscle mass) just as you can use it to aid weight-loss.

IF is about managing appetite mostly, as the hormone that plays a large role in driving hunger (ghrelin) is highly habitual; the more often you eat, the more often you're going to be hungry. So by reducing the time-window in which you eat, you reduce the window when you'll feel hungry, which can dramatically aid diet adherence.

But that's more the everyday form of IF. If you're on a eat-stop-eat type protocol and fast once or twice a week, you're probably using it to ensure you maintain a caloric deficit each week. You're bundling all your reduction in food consumption into one day a week instead of ensuring you're at TDEE-400 calories every day.

Exercise and living a sedentary life are not mutually exclusive. Pretty much everybody on HN has to remain still for most of the day -- however much exercise they do.

Good point. As ever, things are more complicated than they might appear at first...

The ones with diabetes are usually bred that way in order to study the disease. A friend told me about a strain of rats that is literally so prone to obesity they will start eating themselves if no food is available.

Sure...makes sense. Humans have very often resorted to cannibalism when faced with death-by-starvation conditions.

I meant that that one rat would literally start eating parts of its own body. Or that's what I understood from her (she was a biologist).

Yeah, the story about lab mouses which came from farms already with diabetes is good one.

But it seems that it is one extreme case. Another extreme would be stories about wandering (note that "wandering") Indian ascetics, who had very modest and not regular meals (low calories, not abundant) but display a very good fitness (compared to average consumers).

The truth is still out there.)

You mischaracterize calorie restriction with optimal nutrition by calling it starvation, and you mischaracterize the current research situation.

The evidence for it to extend healthy, mean, and maximum life span in a wide range of species is very extensive: mice, flies, nematodes, etc, etc, etc. The primate evidence for life span extension is mixed at this time, partially because the two decades-long studies were poorly designed in hindsight, and the expectation is that it doesn't extend life greatly in humans. Nonetheless, it has enormously impressive short term health effects in we primates [1]. If calorie restriction was a pill rather than a lifestyle, you'd beat a path to the manufacturer's door, as it has far greater positive effects on health for basically healthy people than any presently available medical technology.

It is true that there is some concern in the research community over the degree to which laboratory mice are not good reflections of what is being studied. This is not unknown, and it is not unacknowledged. A range of rigorous testing programs aim to do something about past less rigorous results - see for example the NIA Interventions Testing Program [2].

Interestingly it is worthy of note that many past research programs were tainted by inadvertent calorie restriction - the things they tested led to led to lab animals eating less. The effects of calorie restriction on health and life span are many times larger than those produced by most other things under testing.

To address your subtext of animal abuse, the only thing worse than running animal studies to advance medicine and life science knowledge is to not run those studies. Even the path to the future in which near all studies are carried out in tissue engineered flesh or simulation, causing no harm to creatures capable of suffering, requires present animal studies. Researchers want that future as it is better on all counts. Further, studies of calorie restriction and longevity are about the most benign of animal studies: these animals are healthier and longer-lived as a result of the restriction. If you want to do something about animal suffering, farming is the place to start, not research, as it accounts for 99.9% of the harms you dislike.

[1]: http://impactaging.com/papers/v5/n7/full/100581.html

[2]: http://www.nia.nih.gov/research/dab/interventions-testing-pr...

Is it OK to try to establish a correlation between calorie intake and lifespan without taking into account variety in calorie spending, or a "life style"?

It seems that excess of calories have a big negative effect for an "idle/aged" lifestyle, and almost no effect for "hyper-active/young" lifestyle.

It seems also related to urban vs. rural populations.

Calorie restriction still works in mice in cages with wheels (they often run 6 miles per night). I do not know if it has been tried with different numbers of mice per cage or in "enriched" environments.

See for a very good review: http://jn.nutrition.org/content/137/4/1078.full

But I do acknowledge your underlying point -- that it is exceedingly difficult to know how well results from mouse studies can be generalized to humans. It is a big problem.

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.

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.

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

This is the standard antagonistic pleiotropy hypothesis. While there are some examples of specific proteins and pathways that work this way (beneficial in early life, detrimental in late life), it is far from certain that this is the key driver of aging in evolution (for animals in general, as well as for humans specifically).

For one thing, even in primitive human societies, the life expectancy is well into the 30s or higher (after you discount infant and early-life mortality). Yet aging starts rapidly deteriorating physical capabilities in the mid 20s.

Secondly, one of the key definitions of aging is decreasing resilience with increasing age: so in reality, you cannot treat average lifespan as if it is a constant and the rate of aging is evolutionarily determined from that. Even in primitive man, which died of predation and infectious disease primarily, aging makes older humans much more susceptible to these things (physically weaker and weaker immune system).

Finally, antagonistic pleiotropy does not explain why different organisms have very different maximum lifespans (in protected conditions), and some do not seem to appreciably age at all.

Some more detailed criticisms: http://www.programmed-aging.org/theories/antagonistic_pleiot...

Antagonstic pleiotropy probably plays some role, but it is a needlessly complex explanation when a simpler one exists: the body is a system, and over time, systems degrade and components are damaged. Its ability to repair this damage is considerable, but finite, since the repair mechanisms themselves can become damaged.

This way of thinking assumes that all life is evolved for maximum reproductive fitness. This is false. It is bedrock evolutionary biology, but it is also false. It turns out that the way evolution works is much more subtle than the postulates of R. A. Fisher's system, which dominated evolutionary thinking during the 20th century. Here is a good read on the subject: http://aeon.co/magazine/science/why-its-time-to-lay-the-self...

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.

"aging scientists"

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%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.

>all my scientific alarms go off

Is it required on HN that every article be terse list of peer-reviewed facts?

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'.

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.

It's like citing Bible verses for fundamentalist positivists, so yes.

Never mind that the quality of published research itself varies wildly, or that this requirement creates an intrinsic tunnel-vision bias toward premature convergence at local maxima. If the measure of veracity is citations, then that creates a network effect, etc.

Not saying citations are a bad thing, just that they're not prima facie indicators of truth or rationality.

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.

In answer to your questions:

The 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

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://www.ncbi.nlm.nih.gov/pubmed/23281153

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.

> 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.

"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?

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?

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.

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?

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-demis...

http://whyevolutionistrue.wordpress.com/2013/02/27/another-c...

Is there a way to explain the aging process using the selfish gene theory? I suppose that's what you're hinting at.

Yes it is called the disposable soma theory [1].

1. http://en.m.wikipedia.org/wiki/Evolution_of_ageing#Disposabl...

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.

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).

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.

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.

By resources I wasn't necessarily referring to calories consumed. I was thinking of something like stem cells or some other resource useful for repairing damaged tissues that might be deliberately restricted or "turned off" by the body as part of the process of shutting down overall growth.

The rate of aging seems to be tied to the rate of growth with slower growing organisms also aging more slowly so you might expect GH-deficient mice to live longer if it resulted in a slower rate of growth.

Hopefully turning growth back on for a short period of time would not result in the body actually growing larger in size. With luck, resources made available by new growth would go to repair tissues damaged by aging before initiating new growth.

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.

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.

"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.

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.

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

[2]: http://www.senescence.info/aging_theories.html

[3]: http://sens.org/about/leadership/research-advisory-board

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

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.

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.

"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.

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.

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.

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.

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

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/

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.

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.

"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...

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.

> Basically, calorie restriction works, and nothing else does

We don't even know that for sure. There were two big studies in rhesus monkeys which disagreed on that.[1] Evidence from mice, where this idea originated, is dubious at best considering the mice most studies use.

[1] http://www.nytimes.com/2014/04/02/science/a-new-salvo-in-deb...

The author of this article has a site where he summarizes his suggestions to slow aging http://agingadvice.org/

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.

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.

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.

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?

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.

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.

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.

>It is by definition unsustainable.

Why ? What stops mankind to go in space in go grow further in other planets and systems in the future ? There's AMPLE space for growth everywhere, if anything.

This is not true. No amount of space suffices for exponential growth.

Hubble length is less than 10^24 km. Earth radius is more than 10^3 km. Therefore there's at most room for 10^21 growth in one dimension, 10^63 growth in three dimensions. 10^63 growth is less than 210 doublings. Doubling is less than 70 years of 1% growth per year. 210 * 70 is less than 20,000. Therefore, we can't grow more than 20,000 years, 1% growth per year.

who talks about exponential growth ? Ongoing growth can be linear and has no need to be exponential. Nice strawman.

The way politicians describe growth, it is implicit that it is exponential. More people, producing more offspring, living longer, and using more resources, as more of them become middle class.

Well the tech isn't there for starters. Not in the foreseeable future either. Meanwhile the population continues to grow, the seas are over-fished and getting fill of plastic, the earth gets hotter, the rainforests are being destroyed. Energy from oil isn't going to last forever.

Yes all is fine and dandy, once we set up colonies on the moon.

> Meanwhile the population continues to grow

Population is very much expected and planned to grow up until 10 billions and then stagnate and decrease progressively. Not everyone on earth has tons of kids anymore, it's very much linked to the level of life. See Rosling's speech on the matter for a more detailed explanation.

The Earth does not get hotter by the way, we have like virtually no long term data on the temperature of the Earth and we should actually be VERY humble as to our ability to predict long term climate trends.

And the environment is currently being destroyed with the current population of 7 billion. Add another half again, and you think its all fine?

And 97% of scientists agree that climate change is happening, and is probably caused by man.

> And 97% of scientists agree that climate change is happening, and is probably caused by man.

You know, 97% of scientists believed that the Sun rotated around the Earth not too long ago, so "consensus" is rarely telling.

You are correct that they aren't entirely correct in their predictions. So far global warming has been greater than what they predicted a few years back.

> And the environment is currently being destroyed with the current population of 7 billion. Add another half again, and you think its all fine?

Yup, will be fine. In the early 20th century people said we would all starve when we reach 1 billion people. Look how far we have come without major starvation (apart from the ones causes by civil wars or Communism)

Well, solar energy is also by definition unsustainable - the Sun will die in a few billion years, right?

Our growth is sustainable for the foreseeable future, so I'd say let's first make ourselves immortal and then tackle on the issue of stagnating growth.

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.

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.

I suppose in a way that is correct, but I was refeering to getting the actual animal to live for a long time.

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.

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.

At least it will probably be interesting either way.

Not really. Life expectancy at birth has steadily climbed:

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.

> 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.

> 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.

> A better approach for this is government to fund researchers for areas that private sector has abandoned.

yeah, like Ebola research funding done by the government ? That was an efficient model.

> no real progress

but surely we've been accumulating knowledge and engineering abilities that will enable progress in those areas. It may enable the progress just by being a stepping stone. That is a kind of progress. (Note that I'm not saying we've been accumulating these as fast as we could have been).

Vaccination certainly has prolonged life in the last century.

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.

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.

You need not be a scientist to understand aging.

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_ar...

This is a result of more than year of research by the Author.

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.

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.

> 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?

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.

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.

> 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...)

I remember reading that even if we found a cure to ageing, our life expectancy would "only" be around 10 000 years because of various accidents (car crashes being probably the most major contributor).

If we cure aging, we will become much more cautious.

It sure seems this is the current trend. However, I am not sure that after a few millennia, people would not get bored and start experimenting with more extreme activities like base jumping or space travel.

Or even better, do we actually want to increase the maximum lifespan, or simply stop the body decay for as long as possible? I'd rather live 80 years in a body that worked as if it was still in its thirties, than 500 years in a senescent body.

Do you want to live forever? In a world where everyone lives forever? I'm pretty sure most people will have had enough after the first million or so years.

Someone must have written sci-fi of this.

http://www.multivax.com/last_question.html

A brilliant short story by asminov also briefly touches living forever and running out of space as it were.

I'd like to be able to choose when I die.

and what number would you choose ? waitbutwhy had an interesting discussion on this a few weeks back: http://waitbutwhy.com/table/how-long-would-you-live-if-you-c...

Thanks for the link. I think this is a fascinating question.

In Ian Banks Culture novels, the post-scarcity super-advanced civilization has lifespans of around 350 years (IIRC). They could be longer, but don't for cultural and social reasons. With Culture stories though, I'm never quite sure if Culture society has genuinely agreed on it's conventions freely, or if they are the result of subtle manipulation by the Minds (hyper-intelligent AIs that run the ships and habitats that host the Culture's biological population).

For me if a population of immortals means a population without children I'm not sure it's such a great idea. I'm concerned about intellectual, cultural and technological ossification and ultimately degeneration without a continually renewing population.

From a moral point of view, I don't buy the idea that death is something horrific to be avoided at all costs. Historically it's generally been accepted that there are things worth dying for, and countless throngs have sacrificed their lives, or at least willingly risked them, for causes they believed in. I'm specifically reminded of the case of a father a few years back that leaped in front of a lorry to push a child to safety, obviously knowing that he was sacrificing his own life to do so.

Human life is precious and valuable, but not infinitely so and it's not obvious to me that an existing life is necessarily more valuable than a potential new one. I don't expect it will be politicaly possible or desirable to suppress life extending treatments and I don't really have any idea how this will all play out, but for me it's not a foregone conclusion that a future in which it is normal to indefinitely extend life is an ideal one.

People could have opted for indefinite life-span if they so chose: http://en.wikipedia.org/wiki/The_Culture#Death

They had lots of children, overpopulation was not a problem because of huge habitats that hosted billions of individuals (and that were built with relative ease - The Player of Games). Also I don't agree with the intellectual degradation argument, it's just silly in the Culture AGI context.

Whatever the value of life I think it's best for the individual to decide what to do with it. Most would probably euthanasiate after a while anyway. I would very much prefer suicide than a random age related problem, but I don't really have a choice do I?

I think the worst part of being immortal will be having to deal with so many old people who will berate you for 'not growing up'.

Peter Hamilton's Commonwealth Saga has a pretty good treatment of the subject. His society has rejuvenation treatments that take care of aging bodies as well as artificial memory/personality backups. You age, you go through a rejuve, you die of unnatural causes, your insurance grows you a clone body and dumps your memories in from backup. Pretty interesting consequences. They also have wormhole technology and a budding star empire, so population expansion is not really an issue.

Our species changes a little bit with every generation, it's called evolution, delaying or canceling this process will have negative effects on our specie because it will stop adapting at our constantly changing environment, we might live longer as an individual but we might die as a specie breaking something we don't understand.

That purpose may be "kill the old to make sure the world keeps changing, make sure new genetic experiements (ie. kids/offspring) get a chance". As we hopefully all know, nature isn't afraid to kill off a few people to get more useful experiments (how many animals die trying to have sex, for instance. That is not "necessary")

Early animals didn't age, nor did they die. Some plants don't age (they still die due to illness or trauma, but not through old age). Even "mortal" animals today are offshoots of a central cell-line that doesn't age (ovi in women get their age reset upon birth then no longer age. Sperm get their age reset upon production. This goes for all animals that age, not just for humans). So you are immortal, in the sense that some of the cells that form part of your body won't age and die like the rest of you.

I agree - take a look at http://www.amnat.org/an/newpapers/SepMitteldorf.html http://mathforum.org/~josh/Mitteldorf&Martins_Programmed-Agi...

> Aging is encoded in our DNA with a purpose

Natural selection and evolution has no purpose. It does what works best in its environment. If mankind find that having longer and healthier lives benefits its species, we will probably go that way anyway.

The purpose is survival, failing to adapt means extinction.

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