Wednesday, October 26, 2011
Another field within biology that focuses heavily on understanding aging is biogerontology. Biogerontology focuses on understanding the mechanistic basis of aging at the cellular and molecular level. They describe aging as a process of narrowing of the homeodynamic space, often due to accumulation of damage. Homeodynamic space is a concept related to homeostasis (the tendency of organisms to push their physiological state back to some optimum), but with the recognition that the goal that the individual is pushing towards, and its options for pushing, change over time. For example, as the cells in an organism accumulate mutations, it becomes more dangerous to allow them to continue replicating, because this could spawn a cancer. So the cells are forced to turn down expression of genes that allow for cell replication. But if your cells are replicating less, then you should be more reluctant to allow apoptosis, programmed cell death, because cells that die can't as easily be replaced. But if you've down-regulated the genes involved in apoptosis, this means infected cells will be less likely to kill themselves, so you need to have a stronger inflammation response, so that white blood cells will be brought to areas of infection and kill the infected cells from the outside. But increased inflammation has all sorts of nasty side effects, which themselves need to be compensated for. Note that I am just making this chain up as an example. The point being that the organism, in order to deal with the accumulation of damage, has to adjust various aspects of its physiology, which can cause damage or challenges to the system, which requires further adjustments. The organism gradually loses wiggle room, paints itself into a corner as it were. When this homeodynamic space gets too small, the organism can't respond to whatever insults (internal or external) come along and gets killed.
Reading papers in biogerontology, I am struck by two things. The first is how naive and outdated their evolutionary assumptions tend to be. For example, they still will state that aging is not observed in the wild because no individual lives long enough to grow old in the wild, an opinion that evolutionary biologists began to reject in the 1960s and have now disproved with data from numerous species from plankton to humans and birds to aphids. But I am also struck by how naive they would think our assumptions about age-specific genes are. They state as one of the basic principles of biogerontology that are no genes whose roll it is to cause aging, or which act at a particular age to regulate the chance of death. You will remember I said that such age-specific gene effects, from unspecified genes, are at the center of much of the theory behind evolutionary demography. Yet biogerontologists know such genes not to exist. So our assumptions about the mechanisms are as naive and simplistic as their assumptions regarding the demography.
This lack of communication, with each field basing its thinking on ideas the other has long since rejected, is common in science. There are simply too many journals, papers, conferences, etc., too many fields that may produce important information, for anyone to keep a useful fraction of an eye on most of them. So the lack of communication between fields is to some extent inevitable, but it does have significant consequences.
This is obvious when we introduce the gerontological observation that gene expression is not highly age specific (at least not late in life) to the evolutionary literature on post-reproductive lifespan (PRLS). Much of the study of PRLS has been motivated by the idea that PRLS shouldn't exist unless post-reproductive individuals do something useful for their younger kin. This idea arises from the evolutionary demographic theory of aging I described above. If an individual has reached the age where it can no longer reproduce, the genes it is expressing at that age should be genes that selection doesn't care about at all, because whether she dies at that age has no effect on how many offspring she has. So mutations that kill post-reproductive individuals should accumulate rapidly, unopposed by natural selection. W.D. Hamilton, a preeminent evolutionary theorist of the mid-20th century, wrote in 1966 that “In the absence of complications due to parental care or other altruistic contributions due to post-reproductives, the [mortality] curve should be roughly asymptotic to the age of the ending of reproduction.” By this he means that as the individual approaches the end of her reproductive period, her chance of dying at each instant should approach 100%. This has been dubbed "Hamilton's Wall of Death." Hamilton's work is influential enough, and his basic logic sound enough, that many of my colleagues still believe we should find the Wall of Death. But in fact we can find PRLS in a huge range of organisms where there is no parental care or anything comparable, and the Wall of Death is nowhere to be found. Hamilton's prediction fails because his model is built around high age-specificity of gene expression, which we now know not to exist. Genes which are being expressed at and after the age of reproductive cessation are the same genes being expressed prior to that age, doing the same things they did prior to that age (except of course reproduction) and so they can't just suddenly cause all sorts of lethal effects. This represents a major constraint on the ways selection can shape the pattern of mortality over age, and we evolutionary demographers are just starting to come to terms with the ramifications of this. When I have time to write another longish post, I'll explain how this leads to a major question in evolutionary demography that I have been thinking about but don't yet have any plausible answer to.
Monday, October 10, 2011
One type of constraint that is particularly hard to build theory around is that natural selection can only favor those traits that exist. That is, a trait may be drastically suboptimal, but if all individuals in the population have that trait, and the genes which determine it cannot easily be altered by mutation such that they allow a higher fitness solution, the population will continue being far from optimal.
A classic example of this type of suboptimality is known as the 'obstetric dilemma.' This is the problem that humans have narrow pelvises and big heads, and the head has to pass through the pelvis during birth. In a (now somewhat out of date but still sound for our purposes) summary of one hypothesis of how humans diverged from our chimply relatives, Kristen Hawkes (the anthropologist behind the Grandmother Hypothesis) described (in 2003) the central role this obstetric dilemma played in human evolution thusly:
* Drying environments in the late Tertiary constricted African forests, making capacities to use alternative foods more advantageous among ancestral apes.
* Bipedalism was then favored because it freed hands for tool use, which
increased success at hunting big animals, and this put a premium
on larger brains.
* But the mechanics of bipedal locomotion limited pelvic width, so brain expansion created an ‘‘obstetrical dilemma’’ requiring most brain growth to be postnatal.
Consequently, children with developing brains were immature longer and were more dependent, for a longer time, on maternal care.
* The care requirements interfered with maternal hunting, so mothers relied on
provisioning from hunting mates. This help from fathers allowed mothers to produce more surviving offspring.
* Thus, parents formed lasting bonds and nuclear families became the fundamental
units of cooperation in which a sexual division of labor served familial goals of production and reproduction.
Now according to this story, variations of which are still supported by the scientific evidence,much of the distinctness of human life-history comes through:
1. The need for large brains and small pelvises
2. Which explains why our babies are so undeveloped
3. Which explains we take so long to mature
4. Which is an important part in explaining why we end up with our social system.
5. Which explains why we live so long.
So the optimality of a narrow pelvis, the optimality of a large brain and the need for
that brain to pass through that pelvis ends up being a central fact of human evolution. And why, we may ask, is it optimal for the baby's skull to pass through the mother's pelvis? The apparent answer is that if there is only one possible trait, that trait is the best of all possible traits.
The pattern of vertebrates expelling their young through their pelvis dates back to
before vertebrates actually had pelvises.
Note that this fish has its gonads above and in front of its pelvic fin. That is a common trait among fish, including the lobe-finned fish from which all terrestiral vertebrates are descended. The lobe-finned fishes had bony feet with which they could support themselves on the sea floor, and the bones in their pelvic fins would eventually be modified by evolution into the legs and pelvis.
Now the first terrestrial vertebrates were amphibians, and like most frogs and salamanders, laid small soft eggs, so it was probably no problem for them to continue having the gonads in front and running a tube through the pelvis to the cloaca. This system only became problematic when the eggs got large and hard, as they are in reptiles like turtles. Turtle people like to talk about "pelvic consraint" when they discuss why turtles don't make bigger eggs.
The only non-fish vertebrates to escape the need to run the babies through the pelvis are those that no longer have ana full pelvis, like whales and most snakes. To my knowledge nobody has managed to invent an alternative outlet, so everybody, including us, has to find one way or another to get through the pelvis. In fact, the only alternative is a human invention, the cesarian section.
This obstetric dillema is a very obvious contraint of the 'no alternative' type. Whenever I get a chance to write another longish post, I'll give an example of a constraint where the lack of alternatives is less obvious because it is genetic rather than anatomical.