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Why Do Cells Age? Extremely Long-Lived Proteins (sciencedaily.com)
69 points by llambda on Feb 5, 2012 | hide | past | favorite | 52 comments



This reminds me of a paper I read a few days ago. Melatonin, when bonded to MT1 receptors, can prevent cell death from neurodegenerative such as Huntingtons and Alzheimer's. The melatonin prevents the mitochondria from releasing an enzyme which lights the fuse on cell death mechanisms. Very, very cool.


Link to paper please...



This is most likely a lesser contribution - and remember this is only of practical interest in very long-lived cells, such as the neurons that never turn over and are as old as you are. Compare this mechanism with failure of the lysosome due to buildup of indigestible lipofuscin, or mitochondrial DNA damage, or the cell being battered by higher levels of surrounding AGEs and amyloid or other aggregates, and so forth.

What this does tend to point out, however, is the very long term need for ways to replace or completely repair currently irreplacable cells. That isn't the low-hanging fruit, but it's the sort if thing to be working in once SENS is realized.

By then, of course, the options will be veering off into the space of molecular manufacturing and medical nanorobotics and synthetic replacements for biological molecular machinery.


As a biologist, this is a major pet-peeve of mine: we don't need "medical nanorobotics". Not only is this a nonsense term, but nature has already provided a much better solution.

It's called an enzyme.

Enzymes are hugely efficient "nanorobots" that don't require science fiction. They "manufacture molecules" all the time, every day, at catalytic rates that would make high-tech manufacturing factories blush.


I always wonder why creating synthetic nanorobots to replace organic ones seems more attractive than learning to control what we already have inside. Maybe it's because of the natural repulsion to biology that most people have...


>I always wonder why creating synthetic nanorobots to replace organic ones seems more attractive than learning to control what we already have inside.

Would you like to reuse a result of a process that went on for millions of years and reverse engineer all evolutionary accretions created by a random mutation process ? It's not hard to figure out why developers don't like that option, if they work maintaining a large codebase they probably have hands on expirience with that kind of work. It's not something I would unleash on my brain.


My theory is because most sci-fi enthusiasts are not biologists. They simply do not understand how powerful enzymes are and prefer to think about synthetic nanorobots instead. Plus it sounds cooler.

You don't need to reverse engineer your entire body to understand a single enzyme. We do it all the time in biology. Furthermore, even if you create something that goes haywire in an unanticipated scenario, your body has good defense mechanisms against biological abnormalities.

It doesn't know what the hell to do to quantum dots or nano-scale inorganic materials


Good point, however we could learn to make the organic bots do what we need them to without having to learn everything else about how they work - kind of like driving a car without knowing how to disassemble its engine. They're also much more tightly integrated into the existing infrastructure...


"Need" is a slippery word, and while it is indeed likely that many or most nanoscale tools of future medicine will be fairly directly derived from cells and cell components, and we could probably achieve all of the design goals for agelessness and disease immunity with those, "medical nanorobotics" is not a nonsense term. It explicitly refers to the design and construction of non-biological nanoscale-featured devices - which is a concept far removed from enzymes. There are some things you can do with these designs that are impossible for presently available or plausible biological machinery.

See, for example:

http://en.wikipedia.org/wiki/Respirocyte

http://jetpress.org/v16/freitas.pdf

http://www.nanomedicine.com/


Everything you linked is still theoretical/hypothetical.

Those links basically prove my point. What you linked is possible right now using biology. We don't need nanorobots to modify DNA, we have enzymes and viruses that work really, really well.


Cells age mostly because of telomere shortening.

http://en.wikipedia.org/wiki/Telomere#Telomere_shortening


Sorta, but I wouldn't classify it as "aging". It's more akin to automated self-destruction after a certain amount of time. Aging implies a slow breakdown of function, whereas the limit imposed by telomeres is more of a binary event.

You're good until you run out of telemoeres, then shit gets crazy and you enter apoptosis because your cell is no longer functioning correctly.


Yes, thank you for correction, I used the wrong word. What I tried to say is that telomere shortening is the main cause of cell destruction, and unless its solved, cell death is inevitable


Sorry to correct you again (I'm a biologist...I can't help it!), but cell death is actually a very good thing. Your cells are programmed to die so they don't turn into cancer, or start degenerating into something equally unpleasant.

Aging occurs because your body becomes less capable of replacing these cells over time, and either replaces with less robust cells or stops entirely. Or you get cancer.


Hey, I always welcome constructive corrections. Btw, I actually attended International Biology Olympiads twice, but it was too long ago for me to remember the details.(Ever since I was too remote from biology)


Awesome! I hope it was a good experience! More people should be exposed to biology, it is very cool and under-appreciated. :)


I think the idea is that cell death isn't the problem. Cells die all the time and get replaced, that's not really a problem.

A problem is cells that don't die, but instead start working poorer.


Or maybe the cells that should die but fail to do so?(cancer cells)


omg, so by achieving immortality we would become a sort of cancer in the grand scheme of things?


Thats why I think we were built by aliens. They put an expiration date in our DNA. :)

We just need to figure out how to diffuse the bomb!


It is pretty amazing how complicated our bodies are, but I think the expiration date is there to prevent overpopulation - if our ancestors didn't die, the planet would be overpopulated with lazy apes who don't evolve cause there's no need to :-).

Once we're smart enough to fully control ourselves and our environment, immortality becomes an advantage - sadly, I don't think we're there yet...

Edit: by immortality, I always mean living longer than ~400 years. I'm pretty sure it's impossible to live forever (sooner or later, you'll die of an accident anyway), but living longer and living without any disease should be great...


1> Current actuarial tables have us dying by 550-650 even if there was no aging. Stuff like car accidents, slipping in the shower, etc.

2> "I think the expiration date is there to prevent overpopulation" implies evolution has a purpose. You know when you work at a company, and the processes just change over time and change over time and 5 years in no one remembers why you file a tps report before going on vacation? That's what evolution is like: Whatever processes happened to survive. That TPS report may have some value, it may be easily replaced by a more logical item, or it may be completely useless. Just the fact the process of filing a TPS report before leaving for vacation exists, doesn't mean it's necessary for the health of the organization.

3> Populations the world over are manually dropping their procreation rates to near replacement levels. I'm sure many people would drop it further if they had a few hundred extra years. http://www.guttmacher.org/pubs/journals/3201400.html


>>It is pretty amazing how complicated our bodies are, but I think the expiration date is there to prevent overpopulation - if our ancestors didn't die, the planet would be overpopulated

That is an argument based on group evolution, largely disproved (some unusual edge cases might exist).

I'd recommend reading "The Selfish Gene", it is an incredibly fun journey in beautiful English (Disclaimer: I'm a non-native English speaker.) It will probably change your world view.


I was assuming, of course, that the drive to reproduce would still be there - but, yes, on a closer look, the reproduction rate would diminish, while evolution would continue for the existing individuals...


Want to create a startup that truly has an impact on the world? Make the breakthroughs needed to deliver immortality.


I think mankind should treat aging as the biggest threat it faces, and pour our every last resource into delivering us from its tyranny. It's like we all have this really slow and really insidious fatal disease (aging) and no one wants to admit that it's beatable.

The downside to immortality is that the wealthy would just keep getting wealthier (since building wealth is at least partly a function of having wealth and having experience accumulating wealth) until eventually they are more important than governments. And the great War of 2188 will be of the nation of Zuckerberg vs the nation of the United States of Buffett, winner gets Earth, loser is expelled to roam space for all time.

Ok, I should drink less coffee. :)


> I think mankind should treat aging as the biggest threat it faces

This is absolutely outrageous.

We are already immortal. My children and my children's children are my continuation. They are me. More than that, your infinite existence is harmful and is a threat to your children, who are essentially you. It's very important that you die. Otherwise, your children will have to compete for resources not only with everyone else, but you as well.

On top of all of that, we all go through phases as we age. Those phases are essential to our maturing and experiencing life. To stop aging is the equivalent of stopping the maturation process and stunting life itself.

Death is as natural as birth. We are born, we grow, we experience, we die. To break that cycle is a perversion in itself and would destroy any concept of humanity that currently exists.

We should fear untimely death, certainly. However, timely death should be embraced as much as birth. It is the completion of a cycle. There is absolutely no need to fear it.


Wow.

My children and my children's children are my continuation. They are me.

No, they aren't.

More than that, your infinite existence is harmful

Citation needed.

Otherwise, your children will have to compete for resources not only with everyone else, but you as well.

Yes, that's why we're so much worse off today than we were when the human population was 100 million.

Death is as natural as birth.

As is a 50% childhood mortality rate, people with bad eyesight being eaten by bears, cancer and Alzheimer's.

To break that cycle is a perversion in itself and would destroy any concept of humanity that currently exists.

Wow.

Aging is terrible. Not only does it cause immense suffering and reduced quality of life, it's the major cause of the impending Medicare fiscal train wreck. Although by your "logic" we could get rid of all of that humanity-destroying medicine and solve that problem...


This standpoint is a common example of an appeal to nature. In my opinion, it is specious reasoning; death may be natural, but that doesn't mean it's virtuous.

Your children are certainly the continuation of some of your genes, but the personality we commonly refer to as 'you' almost certainly does not persist after death.

As for resource competition, my preferred deal is simple - I would like to not be dealloced, and in return I will abstain from copying myself :)


Meh... you're entitled to your opinion. I wont lament the 'threat' to my unborn children's children. Of course if you're content to treat death as 'natural' then you're free to embrace it. I for one wish for eternal life... I can't imagine this ever getting boring.


The current accidental death and non-age based disease mortality still has us averaging a death at around 550-650. It's not forever.


If humans didn't age, weaken and die, would you vote to introduce it?


> If humans didn't age, weaken and die, would you vote to introduce it?

No. My advocacy of aging is based on the fact that it was a balance achieved by evolution. Every piece of evidence we have about aging points to it being a well-balanced and curated process of either evolution or design, whichever you prefer.

There are plants on this planet that live thousands of years. Animals that live hundreds. We are not among them. If you think that's a result of bad luck or some such thing, then I'm sorry, you need to go read a bit about evolutionary biology.

Longevity is a trait, crafted by an evolutionary path and the environment. Our life-spans are not an accident. They are not random. They are optimal.

They might change over time. Get shorter. Get longer. Whatever the optimal solution, I'm for it. However, I'm definitely against treating various parts of our nature as if it is some sort of a disease.


Right. So wisdom teeth, cancer and age-related poor vision are all AWESOME, let's leave those in too.

Evolution doesn't have a purpose. It's just stuff that happened to work out. The fact that really long lived humans don't exist now doesn't mean they shouldn't, it just means they didn't happen to exist in the past and show a particular advantage then that was bigger than the advantages other groups had. It doesn't mean they ever existed, so they may be far MORE optimal.

Evolution trends towards local fitness maximums for given solutions when there is competition for scarce resources. It doesn't find global solutions necessarily, nor does it even get to local maximumums even.


> Right. So wisdom teeth, cancer and age-related poor vision are all AWESOME, let's leave those in too.

There is a difference between a malfunction and a trait. A malfunction happens to some people, but always a minority. All of the things you mention are malfunctions.

Aging happens to all of us. It is a trait. At this point, I'm sounding like a broken record, but there is a mountain of evidence that suggests our lifespan is highly selected for by evolution. Please look up the Red Queen.


Cancer happens in 44% of men.

Wisdom teeth happen in over 90% of people

Age-related farsightedness occurs in EVERYONE (it's caused by continual growth of the lens).

If you even read the blurb of the red queen book, it's "contraversial" aka "usually strung together by a popsci writer"


> Cancer happens in 44% of men.

First, that's still a minority. Second, for the overwhelming majority of that 44%, you can easily categorize it as age related.

> Wisdom teeth happen in over 90% of people

The routine removal of wisdom teeth is unnecessary. It is only a necessity in a very small minority of people.

> Age-related farsightedness occurs in EVERYONE (it's caused by continual growth of the lens).

Uhmm, age related by definition. You do remember what we started to talk about originally, right?

> If you even read the blurb of the red queen book

No need to read a blurb when you read the book itself.

> it's "contraversial" aka "usually strung together by a popsci writer"

Do you frequently judge books without reading them? Oh well.


Yes, these are all age related. And they're all things we leave in. We also prevent tooth decay, which killed a large group of them. Etc.

I DO judge a book by the blurb the writer puts on the cover, yes. If they want to call out a controversial theory (by their own words), I'll wait until real scientists who are in that area look at the idea, not a pop-sci treatment of an idea that isn't actually being tested, especially a book advocating the death of billions.


What if the human brain is nothing more than evolution's play for an immortal creature? Create an animal with the capacity to make itself immortal, churn through them until one of them does. Seed the universe with them. Win.


> What if the human brain is nothing more than evolution's play for an immortal creature?

This makes no sense. There is no intelligence behind evolution. It simply selects for the most optimal outcome. It can't plan for anything. To say that we were imbued with intelligence to achieve some future goal makes no sense. Intelligence was selected for immediately apparent benefits.

If you need to believe in some grand design and intelligence, G-d is your answer. Evolution is not.

As I already said, there are animals and plants that are for all intents and purposes without any upper limit on their lifespan. We are not them. There is a reason for that.


>It simply selects for the most optimal outcome

This is not a reasonable conclusion, and is anthropomorphism as well.

Evolution is the process of changing traits by the process of slightly or greatly more fit creatures for a certain environment happening to survive and breed while less fit creatures did not.

There is no reason behind the way anything is, other than it happened to survive better than the alternatives which tried in the circumstances they were tried in. Things are not optimal at all.


And if death were inevitable but we got to pick the average live expectancy, what would you vote for? 80 years? 100? Perhaps go for a more natural 60-but-with-high-infant-mortality thing? Or perhaps if we push it out to 200 years, that would be more fun. Or 2000 years.

When do you think the ideal death age is?


Ideally, when you want to. If we could actually live "age" 20 indefinitely, we wouldn't be decrepid and weak and tired all the time. We could work to pay our way. We could collectively solve big problems like food and space in innovative ways.


It's worth noting that achieving immortality isn't just about medical breakthroughs.

Even if one were to have "immortal" cells, an accident resulting in fatal physical trauma would likely occur within about 400 years [0].

[0] http://simple.wikipedia.org/wiki/Immortality


Does this estimate account for more and more serious trauma being repairable with future technologies? If the entire body and even bits of brain can be regrown/rebuilt, does that still apply?

("In case of car crash, drop severed head in cryoliquid and take to hospital when convenient, preferably within 10 years")


In addition, behaviour would radically change once body immortality (short of smashed head) was available.

In other words, immortal people would be less likely to base jump, fish beyond Arctic circle, drive without a 5 point seatbelt and helmet, etc. They would use simulators for kicks like these.


The problem is that there is no immediate solution. You could bang away at the problem for the better part of a decade and still be 'almost there.'


You'll be doing fine if you manage to extend people's lives by at least one year per year. Think of it as lowering your burn rate. :-)

Of course, that's easier said than done, but living longer, healthier lives is important.


Solving the 'immortality problem' isn't like grinding in an RPG. You don't slowly increase the maximum lifespan at regular intervals.

Immortality would probably involve solving various different, discrete problems. When I said 'almost there' I meant in solving one of these issues.


The real problem is nobody is even trying. Then they all die.


There is even a clear and concise list of specific goals in biotechnology you could be working on or funding, all of which have many intermediary points of viable product and opportunities for incremental profitability:

http://sens.org/sens-research/research-themes

Use the links in the table in the middle of the page above to find explanations for the layperson, references, etc.




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