Muting questions #5 – Why do we age and die??

Welcome back to our Muting questions series, where just by reading the title we fall into despair and void due to the inability of answering the question, in principle so easy to answer.

Let’s start with why it makes sense asking the question “Why do we age”. As any other physical or biological phenomenon, if it happens it means that it can be explained by the laws of physics. So saying that for us, ageing is natural, doesn’t answer our question at all. Just for the fact that we’re used to it, it doesn’t make it universally true. If ageing is a thing we should be able to explain it or at least we should try to.

I say that we need an explanation not only because this phenomenon happens to everybody (and thus affect us very closely, making it very interesting to study) but because it doesn’t make sense in an evolutionary perspective as well. Let me be clearer: Evolution always promotes traits that improve fitness of an individual, such as its reproductive success during the lifetime. Hence, reducing the lifetime of an organism, by ageing and dying, seems counterintuitive according to evolutionary standards.

Here we see some hypothesis that have been raised to explain this Darwinian’s puzzle.

A pure mechanistic theory has been called “the rate of living theory” based on evidence that molecular processes, cells and more unclearly organisms have an intrinsic error nature in every metabolic process. This means that just for the fact that we’re living our lives and that we live according to the second law of thermodynamic, we can’t be 100% efficient and thus we accumulate errors throughout our lives. The higher our metabolic rate the higher the error rate will be. Thus we expect that organisms at a very old age (relatively to the species) got to the limits of their error-resisting threshold. From that point on they will die due to irreparable error accumulation. This will give 2 predictions: 1 – Individuals should have a lifespan proportional to their basic metabolic rate and 2 – Individuals shouldn’t be able to evolve longer lifespans since they already got to their limits. We won’t go into details, but unfortunately there’s no a lot of evidence supporting these predictions at the organism’s level, the only reason this theory is still around is because it moderatly holds for cell cultures.

Two more evolutionary hypothesis have been advanced to explain ageing. The first one is called “The mutation accumulation hypothesis”. Similar to the previous idea, this theory predicts that individuals accumulate mutations during their lives. But this time, these mutations don’t have an effect on the body until old age. Almost like a switch. We examples of this for example in tumors that are genetically determined by come out only at old age (see figure). This theory says that since these mutations have an effect only at old age, they won’t be negatively selected very strongly simply for the fact that at old age the reproductive success is very low anyway. A relatively mathematical model, which we won’t go into, can simply explain this. What we need to understand is that if these late-acting mutations are not selected against, they will stay in the population and will keep causing ageing and death. Apparently, ageing could be just a consequence of weak selection against ageing itself.

cancer_mutations_degregori
There’s clear tendency to support the mutation accumulation theory. Looking at this simple plot proves it very easily.

The last theory we will go through is “The antagonistic pleiothropy theory”. I know it could appear a mouthful of words but it can be simply explained. Assume a mutation arise that will cause an individual living less but becoming reproductively active earlier in life. This is defined as antagonistic pleiothropy because a single mutation causes 2 effects (ageing and becoming sexually mature earlier) and because the effects on fitness (reproductive success) are opposite, or antagonistic.

So if such a mutation can arise in the population, we can prove, through a mathematical model, that this mutation will become more and more popular simply because it’s advantageous. Intuitively you can understand that if I become sexually mature 2 years earlier I can more offspring even if I die 10 years earlier. This is just due to the fact that young organisms are very sexually active and don’t mind dying young if they can propagate their genes in their younger years. So, this theory predicts that having this mutation is actually good for organisms and so that ageing and dying is actually favored.

Pretty cool huh? There’s no need to say that we still don’t know why we age and consequently die, but we can at least speculate. Different theories can give you different perspectives on life itself. These are powerful, if not muting questions. Let me tell you another story..

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