Theories of Aging

There are three major theories of aging: that is it programmed; antagonistic pleiotropy (don't you just love that term? Should be a band name...); and that is the result of accidental damage accumulating over time. I discussed the first theory in my last post, so I'll look at the other two theories in this one.

Sir Peter Medawar (who won the Nobel Prize in Physiology or Medicine in 1960 "for discovery of acquired immunological tolerance" (along with Sir Frank Macfarlane Burnet, who was Australian - did I ever mention I'm Australian?)) suggested in 1952 that because organisms are exposed to constant sources of DNA damage such as background radiation and toxic chemicals, repair systems will eventually be overwhelmed. As mutations accumulate the cells become less and less capable of maintaining normal metabolism, and eventually they age and die.

A different take was presented by George Williams in 1957. He reasoned that natural selection operates far more strongly on young organisms in the reproductive phase of their life cycle than it does when they have already survived to adulthood and reproduced. So genes which produce traits which are beneficial in early life but damaging in later life (hence the 'antagonistic') are likely to persist and spread in a population. 'Pleiotropy' simply means the control by one gene of several different traits, in this case those that benefit the young and impair the old. So under this theory aging is the price we pay for youthful fitness benefits.

In 1977 Tom Kirkwood propsed the 'disposable soma' theory of aging, which pretty much subsumes the other two theories in a pretty neat way. I'll cover disposable soma in more detail next time; right now I'd better get back to a conference paper I'm writing.

Genes for Aging?

The suggestion that aging might be genetically programmed was first made by Alfred Russel Wallace in 1889. He suggested that "Natural selection…in many cases favours such races as die almost immediately after they have left successors" (Wallace, 1889). The idea is predicated upon the existence of group and/or kin selection; organisms which die free up resources, and if their rate of dispersal is low, the organisms which will benefit from these additional resources are highly likely to be kin.

There are some theoretical problems with this approach; for a start, it invokes the spectre of group selection, which is anathema to most evolutionary biologists. The idea that individuals will sacrifice themselves "for the good of the species" was still being taught when I was in high school (and we don't need to go into how long ago that was; it's enough that I'm still alive!), but is generally discredited today. The major problem with it is that the system is open to cheaters - mutant individuals who accept the sacrifices of others without doing their share. Because cheaters get more resources, they can reproduce more, and cheater genes will spread through the population. Apparent instances of suicidally altruistic behaviour such as birds alerting the rest of the flock to the presence of a predator via an attention-attracting call, can be explained in terms of individual, rather than group good. For a very nice introduction to the research in this area, I highly recommend Matt Ridley's book "The Origins of Virtue".

So group selection segued into kin selection, via William Hamilton in 1964. If, instead of the spoecies as a whole, your sacrifice benefits your genes by preserving copies of them - for example, those in your close kin - the sacrifice might be worth it. And the theory does seem to hold in many situations; you can use it to generate hypotheses which can be tested in the field or lab. But there is always a tradeoff between the benefits to the genes in the original owner, and those in the kin. There's an excellent page on the topic in the Stanford Encyclopedia of Philosophy.

I think that for us to be able to say, with some confidence, that aging is programmed, we need much more evidence than we currently have.

What is aging?

OK, maybe the updates won't be as frequent as I'd hoped! A couple of weeks ago we had an induction week for the new research centre I'm working for. The idea was for everyone involved to get to know each other, and discuss some basic issues in aging research. And the most fascinating question that came up, to my mind, was the simplest: what is aging?

A lot of people (in the literature as well as in general conversation) confound aging with longevity. If you're extending lifespan, the unspoken assumption goes, you must be slowing aging, right? Well, maybe. But you're not directly observing the aging process, so longevity remains a proxy. And yet we have strong gut feelings that there is such a thing as a rate of aging. You only have to look around you to see that some 40-year-olds look older than others. But we're interested in cells, and while it's easy to keep track of the chronological age of cells (how long since last division, how many times the population size has doubled, etc.), there's really no way to visually pick a young-for-its-age cell from its more hard-living fellows. So we turn to biomarkers, a topic I'll have some coherent thought on soon. Probably.