What Is Aging? Most Scientists Still Get It Wrong • Hacker News Board

Re: What Is Aging? Most Scientists Still Get It Wrong

#111

Post by IndianAstronaut » Mon, Jan 05, 2015, 6:18 PM UTC

lars wrote: post #82

IndianAstronaut wrote: post #32

Earlier quoted context omitted.

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.

Re: What Is Aging? Most Scientists Still Get It Wrong

#112

Post by givan » Mon, Jan 05, 2015, 6:28 PM UTC

ekianjo wrote: post #42

givan wrote: post #11

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.

> 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.

Re: What Is Aging? Most Scientists Still Get It Wrong

#113

Post by sbalea » Mon, Jan 05, 2015, 6:32 PM UTC

nicky0 wrote: post #17

sanxiyn wrote: post #13

Earlier quoted context omitted.

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 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.

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.

Re: What Is Aging? Most Scientists Still Get It Wrong

#114

Post by xaa » Mon, Jan 05, 2015, 7:39 PM UTC

gabriel34 wrote: post #96

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.…

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.

Re: What Is Aging? Most Scientists Still Get It Wrong

#115

Post by xaa » Mon, Jan 05, 2015, 7:50 PM UTC

aetherson wrote: post #106

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 bas…

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).

Re: What Is Aging? Most Scientists Still Get It Wrong

#116

Post by Houshalter » Mon, Jan 05, 2015, 8:02 PM UTC

rwissmann wrote: post #108

Houshalter wrote: post #107

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/rever…

"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.

Re: What Is Aging? Most Scientists Still Get It Wrong

#117

Post by xaa » Mon, Jan 05, 2015, 8:03 PM UTC

Htsthbjig wrote: post #5

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…

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.

Re: What Is Aging? Most Scientists Still Get It Wrong

#118

Post by xaa » Mon, Jan 05, 2015, 8:36 PM UTC

jrh555 wrote: post #104

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 mi…

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.

Re: What Is Aging? Most Scientists Still Get It Wrong

#119

Post by jrh555 » Mon, Jan 05, 2015, 10:14 PM UTC

xaa wrote: post #118

jrh555 wrote: post #104

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 mi…

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 reprodu…

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.

Re: What Is Aging? Most Scientists Still Get It Wrong

#120

Post by collyw » Mon, Jan 05, 2015, 11:15 PM UTC

mrfusion wrote: post #91

collyw wrote: post #84

Earlier quoted context omitted.

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…

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.