Breaking through constraints: the origin of ageing

A frequent theme on this blog is the evolutionary underpinning of various concepts in molecular and biomedical sciences. Tomorrow I have an interview for a PhD position researching signalling events in cardiac tissue. So, what is the point in researching this? How can understanding cell signalling events help us to develop drugs for those recovering from heart attacks, for example?

To explain this, we must look at the way that evolution is constrained from producing perfection. There are almost certainly many different ways in which unknown hypothetical mutations could give us better hearts, but they have not spread through the population because of constraints of perfection. The obvious constraint is that mutation is random, and many of the hypothetical mutations may never have arisen. Another constraint is that genes are not isolated from each other, and they have multiple effects throughout the body: a mutation that is beneficial to heart tissue might be harmful to other tissues. Some of the hypothetical mutations may put an unacceptable burden on energy use, even when we're healthy. For an abundance of reasons, including constraints on perfection, we have a limited lifespan, and, perhaps more importantly, a limited section of that lifespan during which our bodies are capable of reproduction. This fact provides another constraint on perfection: mutations that do not show their beneficial characteristics until that section of one's life has passed, will have a much reduced effect on evolution: during the extra years the mutation has given you, there is little you can do to propagate that mutation.

This is reflected in how our bodies are built and maintained, the damage and diseases we suffer from, and our defences against those. The principal diseases that young people suffer from are very rare genetic diseases – a constraint on perfection in the sense that mutation rates can't reach zero without the population being wiped out when an environmental change occurs – and infections from viral, bacterial and parasitic organisms – a constraint on perfection in the sense that those organisms are evolving too, in an arms race with our defences (the immune system) which hasn't yet caught up with them. Children also suffer knocks and cuts, but are excellent at repairing them, with built in blood clotting, bone setting, and damage limitation systems. Otherwise, our organs and tissues are strong and healthy before and during that period where we can reproduce.

Beyond this age things begin to go wrong. The heart weakens, atherosclerotic plaque in the coronary artery approaches critical volume. The result of the heart attack is not entirely dissimilar to trauma in skeletal muscle, and the body employs some similar tactics in repairing the damage: some cells die, some proliferate, the tissue becomes inflamed during the repair process, and scarring may occur. The repair process is therefore far from satisfactory, and the heart is left weak: more than a quarter die within a year of the heart attack, and quality of life is permanently reduced for the majority of patients.

What can we learn from cell signalling then? Well, we can learn what the heart is doing during its feeble attempt to recover. We can see if different patterns of cell signalling (and gene expression) correlate with different prognoses, and therefore find potential targets for drugs to switch on or off. And we can look at what was happening when the heart was being constructed from scratch in the embryo: perhaps it will be possible to fool the heart (or stem cells?) into recapitulating some aspects of that embryonic development, and produce new, strong, and scar free heart muscle.