Not a single one of your ancestors did die in childhood
… But another general quality that successful genes will have is a tendency to postpone the death of their survival machines at least until after reproduction. No doubt some of your cousins and great-uncles died in childhood, but not a single one of your ancestors did. Ancestors just don’t die young!
A gene that makes it possessors die is called a lethal gene. A semi-lethal gene has some debilitating effect, such that it makes death from other causes more probable. Any gene exerts its maximum effect on bodies at some particular stage of life, and lethals and semi-lethals are not exceptions.
- Most genes exert their influence during foetal life,
- others during childhood,
- other during young adulthood,
- others in middle age, and yet others in old age. (Reflect that a caterpillar and the butterfly it turns into have exactly the same set of genes.)
Obviously lethal genes will tend to be removed from the gene pool. But equally obviously a late-acting lethal will be more stable in the gene pool than an early-acting lethal. A gene that is lethal in an older body may still be successful in the gene pool, provided its lethal effect does not show itself until after the body has had time to do at least some reproducing. For instance, a gene that made old bodies develop cancer could be passed on to numerous offspring because the individuals would reproduce before they got cancer. On the other hand, a gene that made young adult bodies develop cancer would not be passed on to very many offspring, and a gene that made young children develop fatal cancer would not be passed on to any offspring at all. According to this theory then, senile decay is simply a by-product of the accumulation in the gene pool of late-acting lethal and semi-lethal genes, which have been allowed to slip through the net of natural selection simply because they are late-acting.
Richard Dawkins, The Selfish Gene. Chapter 3: Inmortal Coils. First Published 1976
What is Aging?
- Aging is often obvious because of a change in appearance.
- We can view aging as a loss of function.
- At the cellular and molecular levels, response to hormones decreases with age.
- Increasing age exponentially increases the risk for disease and death.
The first modern theory of mammal ageing was formulated by Peter Medawar in 1952. This theory formed in the previous decade with J. B. S. Haldane and his selection shadow concept. Their idea was that ageing was a matter of neglect, as nature is a highly competitive place. Almost all animals die in the wild from predators, disease, or accidents, which lowers the average age of death. Therefore, there is not much reason why the body should remain fit for the long haul because selection pressure is low for traits that would maintain viability past the time when most animals would have died anyway.
Medawar’s theory is referred to as Mutation Accumulation. This theory is based on the idea that random, germline mutations occur that are detrimental to overall health and survival later in life. Overall, senescence would occur through a summation of deleterious mutations, and would explain the overall phenotypic damage we associate with ageing.
Medawar’s theory was critiqued and later further developed by George C. Williams in 1957.
Williams eventually proposed his own hypothesis called antagonistic pleiotropy. Pleiotropy, alone, means one mutation that cause multiple effects on phenotype.
Antagonistic pleiotropy on the other hand deals with one gene that creates two traits with
- one being beneficial
- and the other being detrimental.
In essence, this refers to genes that offer benefits early in life, but accumulate a cost later on.
Although antagonistic pleiotropy is a prevailing theory today, this is largely by default, and has not been well verified. Research has shown that this is not true for all genes and may be thought of as partial validation of the theory, but it cuts the core premise: that genetic trade-offs are the root cause of ageing.
In breeding experiments, Michael R. Rose selected fruit flies for long lifespan. Based on antagonistic pleiotropy, Rose expected that this would surely reduce their fertility. His team found that they were able to breed flies that lived more than twice as long as the flies they started with, but to their surprise, the long-lived, inbred flies actually laid more eggs than the short-lived flies. This was another setback for pleiotropy theory, though Rose maintains it may be an experimental artifact.
Antagonistic pleiotropy suggests that genes have different effects at different stages of life. For example, a gene that increases growth and fertility but also increases the risk of cancer in old age means more children but a shorter life span. This gene would still spread in a given population because evolution favors survival of the gene, not the longevity of an individual life. One gene might have two different, unrelated effects (pleiotropy) that are seemingly at odds with one another (antagonistic). Survival of the gene is always given priority over longevity of the individual.
There is a particular gene that codes for a protein known as insulin-like growth factor 1 (IGF-1). High levels of IGF-1 promote growth, allowing organisms to grow larger, reproduce faster, and weather wounds better. That’s a huge advantage in the competition to survive in order to have children. However, in old age, high IGF-1 contributes to cancer, heart disease, and early death, and by that time, the gene has already passed into the next generation. When growth/reproduction comes up against longevity, evolution favors reproduction and high IGF-1 levels. This is the fundamental and natural balance between growth and longevity.
DiNicolantonio and Fung. The Longevity Solution
Consequences of Medawar Theory
… As an aside, one of the good features of this (Medawar) theory is that it leads us to some rather interesting speculations. For instance it follows from it that if we wanted to increase the human life span, there are two general ways in which we could do it.
Firstly, we could ban reproduction before a certain age, say forty. After some centuries of this the minimum age limit would be raised to fifty, and so on. It is conceivable that human longevity could be pushed up to several centuries by this means. I cannot imagine that anyone would seriously want to institute such a policy.
Secondly we could try to ‘fool’ genes into thinking that the body they are sitting in is younger than it really is. In practice this would mean identifying changes in the internal chemical environment of a body that take place during ageing. Any of these could be the ‘cues’ that ‘turn on’ late-acting lethal genes. By simulating the superficial chemical properties of a young body it might be possible to prevent the turning on of late-acting deleterious genes.
The interesting point is that chemical signals of old age need not in any normal sense be deleterious in themselves. For instance, suppose that it incidentally happens to be a fact that a substance
Sis more concentrated in the bodies of old individuals than of young individuals.
Sin itself might be quite harmless, perhaps some substance in the food which accumulates in the body over time. But automatically, any gene that just happened to exert a deleterious effect in the presence of
S, but which otherwise had a good effect, would be positively selected in the gene pool, and would in effect be a gene ‘for’ dying of old age. The cure would simply be to remove
Sfrom the body.
Richard Dawkins, The Selfish Gene.. Chapter 3: Inmortal Coils