“There is no free lunch,’’ Dr. Sharpless said. “We are all doomed.”

September 8, 2006 1:29 PM

The evolutionary reason behind senescence^ is one of the great mysteries of biology. Now cancer researchers may have discovered the key to why we age.
posted by Arthur "Two Sheds" Jackson (57 comments total)

This theory is not entirely new. Some previous evidence described here.
posted by Arthur "Two Sheds" Jackson at 1:31 PM on September 8, 2006

Well, I hope that means they can reverse it, because I am not fond of it.
posted by Astro Zombie at 1:31 PM on September 8, 2006

Using the caret to link to wikipedia articles is frowned upon.
posted by delmoi at 1:33 PM on September 8, 2006

Not by everybody.
posted by Astro Zombie at 1:35 PM on September 8, 2006

Thanks for the links. I learned some interesting stuff.
posted by chudmonkey at 1:35 PM on September 8, 2006

Once our genes are done with us, they dispose of us.
posted by delmoi at 1:35 PM on September 8, 2006 [1 favorite]

Once our genes are done with us, they dispose of us.

Also true of our lovers.
posted by Astro Zombie at 1:37 PM on September 8, 2006

"There is no free lunch"

I wonder if oncogenes evolved in turn with sexual reproduction?
posted by Blazecock Pileon at 1:40 PM on September 8, 2006

I thought the caret wikipedia link was an elegant solution.
posted by papercake at 1:44 PM on September 8, 2006

This is the correct character combination for Wikipedia links:

..
^
posted by mmrtnt at 1:48 PM on September 8, 2006

Get rid of caret wikipedia links with arbitrary text.

It's a lot less annoying.
posted by bob sarabia at 1:49 PM on September 8, 2006

I thought that the evolutionary reason we all die was because it would be counter-adaptive for old genes to hang around to mix with new offspring.
posted by Brian B. at 1:57 PM on September 8, 2006

^
posted by Arthur "Two Sheds" Jackson at 1:59 PM on September 8, 2006

^
posted by Blazecock Pileon at 2:06 PM on September 8, 2006 [1 favorite]

: I wonder if oncogenes evolved in turn with sexual reproduction?

Depends on what you mean by that. I don't tend to think of oncogenes as evolving, since they're more like a disease state of a normal gene (the proto-oncogene). Sexual reproduction does let organisms survive with deleterious mutations, to an extent; mixing different versions of each gene (one version from each parent) can dilute the effect. But the same process also lets those mutations get weeded out much more efficiently than asexual reproduction.
posted by zennie at 2:09 PM on September 8, 2006

I thought that the evolutionary reason we all die was because it would be counter-adaptive for old genes to hang around to mix with new offspring.

According to the wikipedia article it's because mutations, or other genetic properties (Alleles?) that cause harm after reproductive age don't matter in terms of evolution.

But think about it this way, we evolved from single-celled organisms, and we reproduce by creating a single new cell, which grows into a new person. The DNA controls the growth of the cell, but it doesn’t know anything about 'fixing' a person beyond a few simple healing processes which don't put things back how they started anyway.

So once babies are born, what difference does it make what happens to the parents? Nothing really, so there is no evolutionary pressure to extend life beyond a certain point.
posted by delmoi at 2:09 PM on September 8, 2006

“We are all doomed.”

News at 11:00.

Most interesting though.
posted by scheptech at 2:11 PM on September 8, 2006

Using the caret to link to wikipedia articles is frowned upon.

The use of passive voice is also frowned upon.
posted by Iridic at 2:13 PM on September 8, 2006

A classic case of damned if you do, damned if you don't.

Use stem cells to cure diseases at the risk of cancer.
I guess if I were a really smart biodude I'd come up with something that replaces this gene's programming with something that does the balancing act a little better: allow stem cells to divide but instead of senescence figure out how to limit stem cell division to where and when it needs to be used.

Nanobot time!
posted by linux at 2:15 PM on September 8, 2006

Depends on what you mean by that

Genes that kill off adults after they have reproduced and raised offspring can help reduce resource strain for a population of people. This might favor selection of oncogenes, among other senesence mechanisms, all of which help make sexual reproduction work in population biology terms, i.e. to increase overall genetic variability and health in a population.
posted by Blazecock Pileon at 2:15 PM on September 8, 2006

Being doomed is frowned upon.
posted by Pastabagel at 2:18 PM on September 8, 2006

^
posted by Smart Dalek at 2:20 PM on September 8, 2006

oh snap! some of ya'll just got called out by a n00b!
posted by casconed at 2:28 PM on September 8, 2006

“There is no free lunch,’’ Dr. Sharpless said. “We are all doomed.”

heh...i like that guy.
posted by cgs at 2:29 PM on September 8, 2006

This could be an interesting thread, if only you people would actually talk about what the post is about.

Taking the new scientific finding at face value, how could this happen? It makes perfect sense evolutionarily, if we assume that people without this senescence mechanism had a higher chance of developing cancer as young adults.

Your score in the Darwinian game is how many grandchildren you have. The goal is to have kids, for them to become adults, and then for them to have kids. The more grandchildren you have, the better rated your overall complement of genes are. Based on a generational time of about 20 years (plus or minus) that means that the evolutionary goal is for you to live to about age 40 in reasonable health. By that point, in tribal life, you're either a grandparent or you aren't.

Thats why Huntington's disease hasn't been bred out of the race: it doesn't start to affect a person until their 40's, usually, and by that point the person has already either won or lost the Darwinian game.

So if we have one person who has a higher chance of dying young of cancer but also a chance of living 100 years in reasonable health, and another person who probably will only make 60 years before senescence sets in but whose chance of getting cancer when young is far lower, evolution favors the latter person.

There's an interesting factoid about mammals: based on an internal clock, the heart, all mammals live about the same length of time. Over a normal lifespan, the number of times the heart beats is about the same for all mammals.

Except for one: modern technological humans live about twice as long as they should. We're preprogrammed to live about 40 years, because that's how long it takes to win or lose the Darwinian game. What happens to us after that doesn't matter in terms of the Darwinian game.

People with the senescence gene are more likely to reach age 40 in good health, and that's why it's been selected for. (Of course, it isn't just humans; this gene goes back a very long way.)
posted by Steven C. Den Beste at 2:32 PM on September 8, 2006 [1 favorite]

Using the caret to link to wikipedia articles is frowned upon... especially when the word itself is linkable, like this:

...senescence...

Heard about this on NPR. Does anyone else remember that article linked here a while back using an extended metaphor comparing death to a giant dragon which we sacrifice our old and aging to?
posted by muddgirl at 2:36 PM on September 8, 2006

dorkus/

Once our genes are done with us, they dispose of us.

Also true of our lovers.

I much rather we dispose of our jeans in the prescence of our lovers.

/dorkus
posted by CynicalKnight at 2:39 PM on September 8, 2006

cgs beat me to it.

MetaFilter: There is no free lunch. We are all doomed.
posted by GuyZero at 2:40 PM on September 8, 2006

an extended metaphor comparing death to a giant dragon which we sacrifice our old and aging to?

That article would almost certainly be this one by Nick Bostrom.
posted by sonofsamiam at 2:41 PM on September 8, 2006

Just for SvdB, I'll make a real comment.

So, if the levels of this protien in old people is so high, how come they still get cancer? And the article seems to take for granted that cancer is "inevitable". This, to me, seems odd. Why is it inevitable? And couldn't we do something to change the levels of this protein in the body to counteract its effects?

Also, some diseases of age are truly wear & tear based. You soak up a lot of UV radiation over your life - cataracts, melanoma, generally saggy skin - I don't see how any of that is caused by this protien. Though perhaps I've missed the connection.
posted by GuyZero at 2:45 PM on September 8, 2006

I always thought we aged because of entropy. Silly me.
posted by ZenMasterThis at 2:55 PM on September 8, 2006

ZenMasterThis, if we aged because of entropy, how come we give birth to youthful offspring?
posted by Arthur "Two Sheds" Jackson at 2:58 PM on September 8, 2006

So, if the levels of this protien in old people is so high, how come they still get cancer?

Simple. Cell reproduction can be likened to a game of "telephone"; after so many-odd reiterations, some information gets disorted. The delicacy of cell structure isn't affected solely by random errors; inherited genes, and metabolic changes spurred by injury, lifestyle, diet, body changes due to other illnesses play a role as well, in varying degrees. Chemicals, radiation, gasses and the like can raise the likelyhood but not necessairily the definate chance of contracting cancer; finding a vaccine or unified treatment becomes difficult, as the history and progress will greatly vary on a per-person basis. The ground gained in catching up is through careful observation and better understanding of the body's limits in cell longevity, durability, and propagation.
posted by Smart Dalek at 3:08 PM on September 8, 2006

Wasn't there a child discovered a few years ago who didn't seem to age? Though she was five or six years old, her mental and physical development had apparently halted in late infancy. I remember that she was covered in a People article, but despite my usually decent Google skills, I'm unable to track her down. Scientists at the time seemed to think that after they'd found out what went wrong with her genes, they'd be able to apply what they'd glean to the general problems of aging.
posted by Iridic at 3:08 PM on September 8, 2006

Wasn't there a child discovered a few years ago who didn't seem to age? Though she was five or six years old, her mental and physical development had

Yes there was.

they'd be able to apply what they'd glean to the general problems of aging.

She still aged, she just didn't grow. Her skin and body had obviously deteriorated the way and adults would
posted by delmoi at 3:15 PM on September 8, 2006

: Genes that kill off adults after they have reproduced and raised offspring can help reduce resource strain for a population of people. This might favor selection of oncogenes, among other senescence mechanisms, all of which help make sexual reproduction work in population biology terms, i.e. to increase overall genetic variability and health in a population.

I have not heard it suggested that oncogenes are a kind of senescence mechanism. They are definitely not a cellular senescence mechanism, since the evidence points to cellular senescence as an anti-cancer process. The underlying question would be, "are proto-oncogenes preserved in an almost-cancer-causing state for the purpose of shortening life-span?" Gut answer: uh... not likely.

: Also, some diseases of age are truly wear & tear based. You soak up a lot of UV radiation over your life - cataracts, melanoma, generally saggy skin - I don't see how any of that is caused by this protien. Though perhaps I've missed the connection.

This gene doesn't cause all forms of aging. Think of it as causing the slow-down part. Normal tissue maintenance requires cell division to regenerate cells, and cell division involves pulling apart and copying genetic material. Mistakes are made in the copying, and there are molecular mechanisms in place to fix them, but they're not always fixed, and over time more and more mistakes are left in... like degradation that occurs when you photocopy a photocopy of a photocopy. You can include the "wear and tear" idea in that too.

When cells undergo fewer divisions, or divide at a slower rate, there is less of a chance that a problem-causing genetic event, like cancer mutation, will occur. So what this gene does as aging progresses (based on what I could get out of the NYT article) is cause the stem cells to stop dividing. The stem cells are like the "originals" in the photocopy metaphor, and even originals do not last forever. Eventually, there are not stem cells to maintain the optimal tissue health, and degenerative disease begins to occur.
posted by zennie at 3:26 PM on September 8, 2006

I read this carefully, and didn't find my theory, which is that the effect of senescence is big at one end, much, much smaller in the middle, and then big again at the other end. At one end, a nearly immortal species wouldn't evolve much at all, since (discounting extrinsic mortality) it would have no strong need or desire to reproduce, and could not compete in the evolutionary race. At the other end, short life spans decrease the time between generations, therefore accelerating the effects of natural selection. Organisms that reproduce quickly and die quickly (like bacteria) should therefore be the most evolved on the planet. And they probably were, in the early days. But they must not be so quick or successful as to put themselves out of business for lack of a host. And their hosts started developing brains. And when the going gets tough, brains trump pure reproductive speed because the evolution of the organism and the evolution of tools, weapons, defense, shelter, food gathering methods, etc. have separated. Since brains take time to develop and assimilate information, natural selection has chosen an optimum life span for highly evolved, intelligent species like humans. The problem we now face is that our tools and weapons have evolved to the point where they will shortly put us out of business unless the brains controlling them start catching up. The bacteria are waiting with bated breath.
posted by weapons-grade pandemonium at 3:48 PM on September 8, 2006 [1 favorite]

It's nice agreeing with SDB 100% for a change.

I've always thought that appendicitis was Darwin's way of clearing the playing field for the younguns (in times of scarcity Darwin wants the food to go to the reproductive generations, not the old folks). Perhaps I picked this up from Dawkins, but I forget.
posted by Heywood Mogroot at 4:16 PM on September 8, 2006

: Since brains take time to develop and assimilate information, natural selection has chosen an optimum life span for highly evolved, intelligent species like humans.

The thing is, compared to most species, most human beings outlive the theoretical optimum. It's the same reason that rats can live longer in captivity than in the wild. Our societies and technology actually allow us to escape our fate, at least for a little while. We are the only species that's been successful in passing down not only genes and basic social memes, but an immense body of applicable knowledge. So while there may be "no free lunch," there seems to be an intelligence-based discount for those in the club.
posted by zennie at 4:29 PM on September 8, 2006

Thanks for this post, Arthur.

How'd you come by two sheds?
posted by goodnewsfortheinsane at 5:10 PM on September 8, 2006

Death.html
posted by owhydididoit at 5:13 PM on September 8, 2006

I read this as good news, at least for those of us who'd like to live a long time (and live healthy during that time). If senescence is a deliberate anti-cancer strategy, that means that curing cancer would also take us pretty far in addressing senescence as well.
posted by bjrubble at 5:42 PM on September 8, 2006

the article seems to take for granted that cancer is "inevitable".

I'm no medical professional or anything, so maybe someone else can come along and be smart at us, but cancer's just unchecked cell growth, right? It's sort of inevitable because, given any amount of time, and the however many million cells in the human body, it only takes a few of them freaking out (i.e. a mutation in one division in the right place) and deciding to uncontrollably divide, and, poof, cancer.

Regulating cell growth and senescence and cancer and certain parts of aging are apparently all tied together, which makes sense. What we'd need to do, to become cancer-proof immortals (ha) is figure out how to stabilize cell growth throughout adulthood so that we're all like 25-year-olds, no longer growing but still quite able to mend and repair. But, like people have said, the wear and tear of being human is hard to avoid.

The life cycle of a body is ridiculously, amazingly complex. We are making progress, though -- and this was a good post.
posted by blacklite at 5:53 PM on September 8, 2006

I've always thought that appendicitis was Darwin's way of clearing the playing field for the younguns (in times of scarcity Darwin wants the food to go to the reproductive generations, not the old folks).

Darwin wants his daughter back. What you said, not so much.
posted by delmoi at 5:58 PM on September 8, 2006

If senescence is a deliberate anti-cancer strategy, that means that curing cancer would also take us pretty far in addressing senescence as well.

Heard this today on Science Friday and was thinking the same thing while reading the news article link.
posted by effwerd at 6:01 PM on September 8, 2006

I'm no medical professional or anything, so maybe someone else can come along and be smart at us, but cancer's just unchecked cell growth, right? It's sort of inevitable because, given any amount of time, and the however many million cells in the human body, it only takes a few of them freaking out (i.e. a mutation in one division in the right place) and deciding to uncontrollably divide, and, poof, cancer.

Not quite, since cancer cells need blood to survive, they need to generate their own networks of blood veins. So not all unchecked cell growth turns into harmful tumors, only certain types. There are also cancers that don't involve tumors. The way to cure cancer is to attack each specific type, which is what's being done. There will never (I believe) be a purely general cure for cancer.
posted by delmoi at 6:03 PM on September 8, 2006

I dunno. There's a theory that says that cancer isn't the disease we think it is.

Most people think that "cancer" is cells which start to grow out of control. But what this theory says is that uncontrolled growth of cells like that happens all the time to everyone. However, in most people the immune system detects it happening and kills off the cells which are out of control.

So the disease we think of as "cancer" isn't uncontrolled growth, it's a failure of the immune system to adequately detect and destroy those cells.

One interesting consequence of this theory is that chemotherapy is just about the worst way to treat cancer, since it tends to hammer any kind of cell which is actively dividing. Hence chemotherapy tends to cause trouble in the stomach and intestines, and it also tends to affect the bone marrow where new blood -- including white blood cells -- is being produced.

The theory suggests that the right thing to do is to study how the immune system detects cancer, and why it sometimes misses it, and to see if there's a way to change it so that it doesn't miss it after all.

If this is correct (or even partially correct) it may well be possible to vaccinate for cancer -- and vaccines for certain kinds of cancers are in testing right now.

And it's not outside the bounds of possibility that a small number of antigens may be discovered which uniquely identify cancer cells of all kinds, and which could be the basis for a general protection against cancer.
posted by Steven C. Den Beste at 6:17 PM on September 8, 2006

I thought the caret wikipedia link was an elegant solution.

To what problem? Seriously, what on earth is broken about linking the word "senescence" instead of introducing the caret *after* the word senescence? The Wikicaret does nothing but draw attention to the fact that a link is to a Wikipedia page. What problem does that solve, exactly?
posted by mediareport at 6:31 PM on September 8, 2006

very interesting---so many people get cancer, but so many people are now living far longer than their ancestors (even their parents and grandparents) ever did--it's really only the past 70? 50? years that life expectancy shot up, no? And we can also recognize and diagnose so many more cancers that we couldn't years ago.

Will there now be a way to regulate this for people who get cancer too early? (if that makes sense)
posted by amberglow at 6:53 PM on September 8, 2006

or following Steven's thing--to create a vaccine for those cancers that are proven to run in families? like the BRCA stuff?
posted by amberglow at 6:55 PM on September 8, 2006

Weird Friday evening thought

What if we "cure" cancer and senesence allowing people to live to 300. What if around, say 150, everyone got some Alzheimers-variant, call it AlzX, that erases their brain completely but for motor function. Once erased, the Alzheimer's thing goes away, and now you have a 150 year old infant, basically, who has to relearn everything, develop a new personality, etc. like ordinary children do. You'd essentially have two people who occupied the same body at different times.

Imagine the social structures that would develop. Friends, or better yet children, of the AlzX patient would hold sort of a funeral for the parent who is lost, but then they become the parent of the nascent personality that forms anew in the erased brain, raising it and shaping it the way any parent does for their children. Each generation does double duty as both child and parent of the previous generation.

Wouldn't that be weird? I think it would be weird. I'm going to finish my pie now.
posted by Pastabagel at 7:52 PM on September 8, 2006

It's actually not that weird--many people end up parenting their elderly parents due to Alzheimers and dementia and other things. The problem tho, would be with all the generations inbetween--if each generation has kids at 20 or 30 or 40, would those people and their kids only be responsible or would everyone inbetween also be responsible? or no one? how could you enforce it?
posted by amberglow at 8:49 PM on September 8, 2006

The Picture of Dorian Gray^{^}

"...what on earth could happen to you, Dorian? You have everything in the world that a man can want. There is no one who would not be delighted to change places with you."

"There is no one with whom I would not change places, Harry. Don't laugh like that. I am telling you the truth. The wretched peasant who has just died is better off than I am. I have no terror of death. It is the coming of death that terrifies me.

posted by cenoxo at 9:36 PM on September 8, 2006

I've always thought that appendicitis was Darwin's way of clearing the playing field for the younguns (in times of scarcity Darwin wants the food to go to the reproductive generations, not the old folks).

When you explain things this way the ID people start hopping up and down, saying "See, see?" Darwin (read evolution) doesn't want anything. Some species get appendicitis, some species don't. The species that don't get appendicitis take the food from the younger generations and therefore are not as successful. They may be just as likely to exist, but not as likely to compete and reproduce, ergo survive. Nobody is pulling appendix strings out there.
posted by weapons-grade pandemonium at 8:05 AM on September 9, 2006

it's a failure of the immune system to adequately detect and destroy those cells.it's a failure of the immune system to adequately detect and destroy those cells. [...]

The theory suggests that the right thing to do is to study how the immune system detects cancer, and why it sometimes misses it, and to see if there's a way to change it so that it doesn't miss it after all.

The Rosenberg tests (spotlighted in the SciFri podcast I linked to earlier) involved genetically engineered lymphocytes to recognize and attack tumors. Only 2 out of 17 had a response but they felt that it was a proof of concept. The two remain disease free after 18 months and still have high levels of the engineered cells in their blood.

Here is another article about the same kind of research.
posted by effwerd at 8:17 AM on September 9, 2006

Steven C. Den Beste

Good points but vaccines aren't going to be the answer for every cancer type. The main problem with targeting tumors with antibodies is that you have to find a specific marker on the tumor which separates it from every other cell in the body, and that often is not the case. Often times you'll find that the tumor has 40% more CD44 (just picking a random marker for example) than the normal cells surrounding it. So you can target the tumor cells to that marker but you're still going to kill a sifginifcant amount of normal cells. And a lot of cancer types they haven't found any significant change in the cell surface receptors that will allow researchers to target the tumors with vaccines.

Also, I'm going to say it is outside the bounds of possibility that they will discover antigens that are common in all cancers. They are just too many different types of cells and too many pathways for a cell to become cancerous for there to be one shared weak link among all cancers. And even if we found one today, by next week we'd find a new form of tumors that's resistant to it. It's how cells work.

As for cancer being inevitable, as far as we know it is because each cell division carries with it a certain error rate. Stop thinking of cancer as a disease so much as "the point at which my cells start losing proper functionality". They accumulate so many mistakes over your lifetime that eventually some are going to start growing unchecked.

(worked in a cancer-immuno lab at sloan kettering for a while, not sure if I have faith in immunology curing cancer in the next 5 years, it's simply way too tricky at the moment)
posted by slapshot57 at 11:30 AM on September 9, 2006

^
posted by Optimus Chyme at 1:20 PM on September 9, 2006