Why do we age?

We’re all familiar with what ageing actually looks like. We all have elderly relatives, et cetera, or are ageing ourselves, grey hair, wrinkly skin. But an interesting issue is why do we actually age? Can we understand it in terms of Darwinian evolution, from an evolutionary point of view? Well, the first thing to consider - is it actually adaptive? Are there good reasons for us to age, and perhaps increase the chances of dying. Well, some people do believe it is, and talk about programme for ageing just like in development. Now in that case, individuals age and increase the chances of dying, are removed from the population, make space for the next generation. It makes sense in evolutionary terms. But does it?

There’s real caveats and problems with that argument. The first thing is that, in the case of humans for example, we would only really drop dead or remove ourselves from the population if we can really benefit our immediate kin, our children, our grandchildren. We wouldn’t voluntarily drop dead for the benefit of unrelated kin. That just doesn’t make evolutionary sense. And in fact for humans, it’s actually not feasible for us to be so directive on how our removal - who would benefit from that. The second reason that programmed ageing doesn’t work is, in fact, in humans, in natural state - natural fertility, natural mortality - there’s very few elderly individuals in those populations just because life is so tough.

There’s very few individuals that reach old age. Selection is actually very weak at old ages. So in fact actually, there’s very little selection on removing those individuals from the population. It sort of just misunderstands the whole process of evolution to propose that a programme can exist for ageing. So what alternatives are there? The first real alternative was proposed in the early ’50s by Peter Medawar. Now, he was thinking about this issue that the force of natural selection declines with age. And he was thinking, well perhaps, over evolutionary time, if certain genes are late-acting and have accumulated mutations over the generations, then perhaps those genes are difficult to remove through the selective process.

And their expression is what we’re seeing, when we see an ageing individual. He had in mind a disease called Huntington’s disease, which is a very serious neurological disorder, that’s created by a mutation in the gene huntingtin. And what he realised was although it’s a very serious disease, the effects are really only observed in ages beyond 40 or 50. Now that is the age in humans after which most people have had their children. So in fact the children have already been born and are maybe even carrying that mutation. And they’ll also be experiencing Huntington’s disease in later age, or at least 50% of them will be.

And so if he extended that to say that perhaps this was true of many genes, what he termed mutation accumulation could account for a large part of ageing. So that was one idea from genetics. An alternative idea was put forward in the late ’50s by a guy called George Williams. He was obviously aware that many genes have pleiotropic behaviour. They act in different ways in different circumstances. And what he thought was perhaps these genes, or in the case of genes that have effects in early life, maybe they have different effects in late life. Beneficial in early life and detrimental in late life, and he termed this antagonistic pleiotropy.

Genes that he was thinking about were genes for - oestrogen, for example - that’s beneficial in terms of fertility early in life, but are detrimental in terms of increased levels of cancer in later life. Another gene that has been mentioned is P53, which is protective in early life against DNA damage, the arrival of cancers, but perhaps is detrimental to tissue function in later life by increasing levels of apoptosis. So these two theories are feasible and perhaps contribute to ageing.

But about 15 years or so ago, through examining the contribution of genetics to ageing in monozygotic and dizygotic twins, researchers were able to establish that only about 25% of differences in ageing can be accounted for by genes, such as through a process like mutation accumulation or antagonistic pleiotropy. 75% of the variation therefore is unaccounted for. So how are we going to deal with this? Well, an alternative way of thinking about this was proposed by Tom Kirkwood in the late ’70s, and he termed this disposable soma theory of aging.

What it’s based on is thinking about individuals, individual humans, as organisms that take in resources - food, micronutrients, et cetera - and partition those resources between different physiological processes of growth, reproduction, maintenance, keeping ourselves in good condition. Obviously in early life, most of the resources go into growth. But on maturity, there’s is a decision on how much resources should go into reproduction, and how much resources should go into maintenance to keep ourselves in good condition so that we live long enough to have several reproductive efforts. And it is that trade-off between reproduction and maintenance that can explain the ageing process.

Basically from an evolutionary point of view, we all need to have babies, and that is at the expense of our maintenance processes. Because after all, resources are finite. This other 75% of variation therefore can be accounted for by differences in the way that these resources are allocated. So what further evidence is there of decisions, plasticity in the way resources are allocated? Well interestingly, there’s a major programme of research that followed on from the discovery in the mid ’30s that if you reduce diet in rodents, you can observe a substantial extension in lifespan.

Basically what seems to be happening is these mice, rats, seem to be shutting down their reproduction and using all their resources in maintenance, enhancing maintenance processes, and keeping themselves in a more youthful condition, and thereby living longer. But these animals are largely infertile. Now are the same processes true in humans? Some humans believe they are. And some people are subjecting themselves to voluntarily caloric restriction, or food restriction, and are constantly monitoring how much they eat per day, and trying to keep their diet at very low levels, severely low levels, about half of what we ideally like to eat, in the hope that they’re going to live a long life.

Now in humans, there’s not a lot of evidence that we are going to benefit like small organisms, such as rodents. Although clearly there will be some initial benefit from the conditions of overeating. So the jury’s out really on whether undernourishment is actually going to benefit us in the same way it has in rodents. The most important issue though to take from this evolutionary argument is that we can explore the plasticity in ageing through this framework of disposable soma theory, for example. And thereby, by doing that, we’re far more confidence in actually proposing interventions in ageing to extend lifespan that makes sense from our biology, our underlying biology, from how it’s been built over evolutionary time.

And if we can do that, of course, then we’ll have far less side effects in any interventions that we actually establish in the future.