nature wants you to die
Oct. 1st, 2014 02:34 pm![[personal profile]](https://www.dreamwidth.org/img/silk/identity/user.png){kind=small}
stormsewerSo, I've been thinking a lot about death lately.
Everyone knows that everything dies, but why? If you're like me you immediately want to shout "ENTROPY," and then sit back and relax to the soothing sounds of your deep understanding of the universe. But if you think a little more deeply you'll realize that that doesn't explain it at all.
For starters, it takes a lot more energy to build an entirely new human body than it does to repair an existing one. As long as the sunlight stays on and the cows still come in from the pasture, there's more than enough free energy around to counter all the effects of entropy on a human body, short of spontaneous combustion. So why are we constantly tossing the old ones on the compost pile and investing all the time and energy to make new ones? There are actually some creatures, like the hydra, that seem to be essentially immortal. So why can't we be?
As with most biological questions, things start to make more sense in the light of evolution.
One answer is cancer. Your body is a communist utopia of cells. If you think that runs counter to Darwinian ideas of competition and survival of the fittest, you're not entirely wrong. While it does turn out that cooperation can be an extremely competitive choice evolutionarily (the details of why are a topic for another post), it is also true that simple facts such as "those who take more get more" and "those who grow faster push out those who don't" remain in force at the cellular level, and sooner or later some renegade, spouting off about rational self-interest and the dangers of collectivism [1] will slip past all the safeguards and start growing exponentially as if its resource base is infinite and it itself is solely responsible for everything good that ever happened to it [2]. And that in turn inevitably crashes the whole system and kills all the cells if it isn't stopped. As your life span goes to infinity, your chances of getting cancer go to 100%. So even if the spontaneous combustion doesn’t get you, cancer will.
But even if we take cancer out of the equation entirely, people's bodies still start breaking down as they get older, and people still die of "natural causes." Why does it have to be that way? Again, if you're like me, you'll likely then say, "Fine, evolution, then. Evolution is about successfully breeding, so it makes sense that once you've done that, you can go to hell for all Nature cares." But that is yet another answer that is simple, neat, and wrong. Or at least incomplete. Because (A), if you stayed alive forever you could keep successfully breeding forever, and (B) slowdown starts well before your reproductive years are over– athletes are typically considered over the hill by 30, for example. So why would nature set it up this way?
The most common scientific explanation these days comes from the observation that, since the longer you live the greater your chances of getting sucked into a jet engine or having your mind consumed by Cthulhu, evolution must have optimized you to maximize your chances of breeding as soon as possible. So if the hacks and quick fixes that were schlepped in to get that to happen cause problems down the line, Nature doesn't really care. They call this the "pleiotropic theory of aging" [3]. A pleiotropic gene is simply one that affects many different traits, so the name comes from the idea that nature favors genes that help you when you're young but have other unintended consequences when you get older.
One of the predictions of the theory is actually that the decline will be systemic and that there will be no obvious fix to achieve immortality, because if it was a simple matter to stay healthy longer without comprising development or fertility, evolution would already have made it so [4]. This also makes it hard to pick out specific examples of the theory in action, but testosterone, which obviously makes young males strong competitors and lively mates but tends to lead to prostate cancer later in life, is probably one. Cancer generally is likely an example, since teaching your cells to grow quickly when young may increase the chances of some of those cells wanting to continue growing quickly when old. Also, the cause of cancer and its onset are often widely spaced in years, which makes it easy for evolution to pick a tweak that gives a fifteen-year-old her boundless energy in exchange for cancer at 50. Insulin-like growth factors are another good example; if you have less of them you live longer but take a hit in fertility (and they're also involved with all kinds of body systems, so trying to mess with them is an iffy idea) [5]. And a number of studies with long-lived worms, flies, and mice have shown that they usually have extra problems earlier in life, especially under non-ideal circumstances like starvation or extreme temperatures [6].
But wait, there's more! Yeast past a certain age have been found to actively commit suicide under starvation conditions. Some very interesting work [7] showed that under such conditions, the suicidal yeast can outcompete strains that live longer. There seem to be two reasons for this: (1) the yeast that die bequeath their nutrients to the young, and (2) long-lived yeast tend to have lower mutation rates, which makes their lineages slower to adapt to changing conditions. The cell-suicide pathways found in these yeast are very similar to those in human cells.
The idea that death is selected for to keep the old from hogging resources that newer, presumably better-adapted generations might use was actually proposed in 1870 or so by Alfred Wallace (the guy who nearly beat Darwin to the natural selection punch) [8]. Subsequent generations dropped the idea under the assumption that creatures generally don't live long enough for it to matter, but that's clearly not necessarily the case, and it's definitely not the case for modern humans. This is something we should consider as we try to push our lifespans to the maximum. Living too long might impede our species's ability to adapt, and make it harder for new generations to find their place in the world. It seems nature wants us to die. And maybe we should, too.
Footnotes
[1] Note: Cells do not actually spout off about rational self-interest and the dangers of collectivism.
[2] I kid, I kid. But seriously, it's surprising how many people in this country have forgotten that selfishness is not the solution to all problems.
[3] The paper that more or less introduced the idea is pretty readable, if you're interested: Williams. Pleiotropy, natural selection, and the evolution of senescence. Evolution 11: 398-411 (1957).
[4] This is something to keep in mind when talking about doing genetic engineering to make humans or some other organism "better." If it's really better, why didn't it evolve to be that way in the first place? Sometimes the genetic engineers have a good answer to this question, and sometimes they don't. I'm certainly not trying to say that gene therapy or genetically modified organisms are necessarily a bad thing, but if we want our genetic tweaks to work out, it's important to remember that things are the way they are for a reason. In his article (see footnote 3), Williams drops this little gem: "This conclusion banishes the 'fountain of youth' to the limbo of scientific impossibilities where other human aspirations, like the perpetual motion machine and Laplace's 'superman' have already been placed by other theoretical considerations. Such conclusions are always disappointing, but they have the desirable consequence of channeling research in directions that are likely to be fruitful." For a long time longevity research has indeed been a backwater, and though that has changed recently, the philosopher's stone has yet to appear...
[5] Carter et al. A critical analysis of the role of growth hormone and IGF-1 in aging and lifespan. Trends Genet. 18, 295–301 (2002).
[6] You know you want references. Here's some to get you started:
Walker et al. Natural selection: Evolution of lifespan in C. elegans. Nature 405: 296-297 (2000).
Marden et al. Conditional tradeoffs between aging and organismal performance of Indy long-lived mutant flies. PNAS 100:3369-3373 (2003).
Kurosu et al. Suppression of aging in mice by the hormone Klotho. Science 309: 1829–1833 (2005).
Casanueva et al. Fitness Trade-Offs and Environmentally Induced Mutation Buffering in Isogenic C. elegans. Science 335: 82-85 (2012).
[7] Fabrizio et al. Superoxide is a mediator of an altruistic aging program in Saccharomyces cerevisiae. J Cell Biol 166:1055-1067 (2004).
[8] Not published until it was quoted in August Weissman's Essays upon Heredity (1889), specifically the first essay, "The Duration of Life," dated as 1881.
Everyone knows that everything dies, but why? If you're like me you immediately want to shout "ENTROPY," and then sit back and relax to the soothing sounds of your deep understanding of the universe. But if you think a little more deeply you'll realize that that doesn't explain it at all.
For starters, it takes a lot more energy to build an entirely new human body than it does to repair an existing one. As long as the sunlight stays on and the cows still come in from the pasture, there's more than enough free energy around to counter all the effects of entropy on a human body, short of spontaneous combustion. So why are we constantly tossing the old ones on the compost pile and investing all the time and energy to make new ones? There are actually some creatures, like the hydra, that seem to be essentially immortal. So why can't we be?
As with most biological questions, things start to make more sense in the light of evolution.
One answer is cancer. Your body is a communist utopia of cells. If you think that runs counter to Darwinian ideas of competition and survival of the fittest, you're not entirely wrong. While it does turn out that cooperation can be an extremely competitive choice evolutionarily (the details of why are a topic for another post), it is also true that simple facts such as "those who take more get more" and "those who grow faster push out those who don't" remain in force at the cellular level, and sooner or later some renegade, spouting off about rational self-interest and the dangers of collectivism [1] will slip past all the safeguards and start growing exponentially as if its resource base is infinite and it itself is solely responsible for everything good that ever happened to it [2]. And that in turn inevitably crashes the whole system and kills all the cells if it isn't stopped. As your life span goes to infinity, your chances of getting cancer go to 100%. So even if the spontaneous combustion doesn’t get you, cancer will.
But even if we take cancer out of the equation entirely, people's bodies still start breaking down as they get older, and people still die of "natural causes." Why does it have to be that way? Again, if you're like me, you'll likely then say, "Fine, evolution, then. Evolution is about successfully breeding, so it makes sense that once you've done that, you can go to hell for all Nature cares." But that is yet another answer that is simple, neat, and wrong. Or at least incomplete. Because (A), if you stayed alive forever you could keep successfully breeding forever, and (B) slowdown starts well before your reproductive years are over– athletes are typically considered over the hill by 30, for example. So why would nature set it up this way?
The most common scientific explanation these days comes from the observation that, since the longer you live the greater your chances of getting sucked into a jet engine or having your mind consumed by Cthulhu, evolution must have optimized you to maximize your chances of breeding as soon as possible. So if the hacks and quick fixes that were schlepped in to get that to happen cause problems down the line, Nature doesn't really care. They call this the "pleiotropic theory of aging" [3]. A pleiotropic gene is simply one that affects many different traits, so the name comes from the idea that nature favors genes that help you when you're young but have other unintended consequences when you get older.
One of the predictions of the theory is actually that the decline will be systemic and that there will be no obvious fix to achieve immortality, because if it was a simple matter to stay healthy longer without comprising development or fertility, evolution would already have made it so [4]. This also makes it hard to pick out specific examples of the theory in action, but testosterone, which obviously makes young males strong competitors and lively mates but tends to lead to prostate cancer later in life, is probably one. Cancer generally is likely an example, since teaching your cells to grow quickly when young may increase the chances of some of those cells wanting to continue growing quickly when old. Also, the cause of cancer and its onset are often widely spaced in years, which makes it easy for evolution to pick a tweak that gives a fifteen-year-old her boundless energy in exchange for cancer at 50. Insulin-like growth factors are another good example; if you have less of them you live longer but take a hit in fertility (and they're also involved with all kinds of body systems, so trying to mess with them is an iffy idea) [5]. And a number of studies with long-lived worms, flies, and mice have shown that they usually have extra problems earlier in life, especially under non-ideal circumstances like starvation or extreme temperatures [6].
But wait, there's more! Yeast past a certain age have been found to actively commit suicide under starvation conditions. Some very interesting work [7] showed that under such conditions, the suicidal yeast can outcompete strains that live longer. There seem to be two reasons for this: (1) the yeast that die bequeath their nutrients to the young, and (2) long-lived yeast tend to have lower mutation rates, which makes their lineages slower to adapt to changing conditions. The cell-suicide pathways found in these yeast are very similar to those in human cells.
The idea that death is selected for to keep the old from hogging resources that newer, presumably better-adapted generations might use was actually proposed in 1870 or so by Alfred Wallace (the guy who nearly beat Darwin to the natural selection punch) [8]. Subsequent generations dropped the idea under the assumption that creatures generally don't live long enough for it to matter, but that's clearly not necessarily the case, and it's definitely not the case for modern humans. This is something we should consider as we try to push our lifespans to the maximum. Living too long might impede our species's ability to adapt, and make it harder for new generations to find their place in the world. It seems nature wants us to die. And maybe we should, too.
Footnotes
[1] Note: Cells do not actually spout off about rational self-interest and the dangers of collectivism.
[2] I kid, I kid. But seriously, it's surprising how many people in this country have forgotten that selfishness is not the solution to all problems.
[3] The paper that more or less introduced the idea is pretty readable, if you're interested: Williams. Pleiotropy, natural selection, and the evolution of senescence. Evolution 11: 398-411 (1957).
[4] This is something to keep in mind when talking about doing genetic engineering to make humans or some other organism "better." If it's really better, why didn't it evolve to be that way in the first place? Sometimes the genetic engineers have a good answer to this question, and sometimes they don't. I'm certainly not trying to say that gene therapy or genetically modified organisms are necessarily a bad thing, but if we want our genetic tweaks to work out, it's important to remember that things are the way they are for a reason. In his article (see footnote 3), Williams drops this little gem: "This conclusion banishes the 'fountain of youth' to the limbo of scientific impossibilities where other human aspirations, like the perpetual motion machine and Laplace's 'superman' have already been placed by other theoretical considerations. Such conclusions are always disappointing, but they have the desirable consequence of channeling research in directions that are likely to be fruitful." For a long time longevity research has indeed been a backwater, and though that has changed recently, the philosopher's stone has yet to appear...
[5] Carter et al. A critical analysis of the role of growth hormone and IGF-1 in aging and lifespan. Trends Genet. 18, 295–301 (2002).
[6] You know you want references. Here's some to get you started:
Walker et al. Natural selection: Evolution of lifespan in C. elegans. Nature 405: 296-297 (2000).
Marden et al. Conditional tradeoffs between aging and organismal performance of Indy long-lived mutant flies. PNAS 100:3369-3373 (2003).
Kurosu et al. Suppression of aging in mice by the hormone Klotho. Science 309: 1829–1833 (2005).
Casanueva et al. Fitness Trade-Offs and Environmentally Induced Mutation Buffering in Isogenic C. elegans. Science 335: 82-85 (2012).
[7] Fabrizio et al. Superoxide is a mediator of an altruistic aging program in Saccharomyces cerevisiae. J Cell Biol 166:1055-1067 (2004).
[8] Not published until it was quoted in August Weissman's Essays upon Heredity (1889), specifically the first essay, "The Duration of Life," dated as 1881.
