Why die?

A very interesting paper in PLOS Biology makes a convincing case that a mutation in a gene called APOC3 is linked to long life in people. Nir Barzilai, of the Albert Einstein College of Medicine, and his team looked for this particular genetic needle in a haystack of 214 centenarians. This was smart, because centenarians are obviously long-lived; if there is a genetic basis for longevity, it should show up. They further reduced the haystack by selecting their centenarians from Ashkenazi Jews. Historical and genetic evidence suggests that all Ashkenazi Jews descend from a small population of about 30,000 people about 500 years ago. The small original founder group means that the population today is more genetically uniform than people selected at random, improving the odds of being able to link a particular genotype with survival to exceptional old age.

The old folks have obviously avoided most types of cardiovascular disease and previous studies indicated that this would be a good area in which to seek genetic differences. The team measured several markers of heart disease, such as blood lipids, “good” and “bad” cholesterol, insulin and others. They also measured single-nucleotide polymorphisms (SNPs) in 36 genes associated with lipid metabolism.

One mutation of APOC3 was much more common in the centenarians. More than a quarter of the centenarians had two copies of the mutation. Of their children, 20% had the mutation. But among an unrelated sample, matched in age to the children, a rather neat way of getting round the difficulty of finding suitable controls for their ancient parents, fewer than 1 in 12 had the mutation.

All this is very nice, and illuminating. APOC3 is one of many genes involved in lipid metabolism, all closely linked to one another on chromosome 11. If it isn’t the actual gene “for” longevity, one of the others will be. But what surprises me is that nowhere in the paper or the commentaries on it I have seen do the authors discuss the evolution of longevity.

Or to put it another way: why do living things die?

Richard Dawkins has a good explanation of Sir Peter Medawar’s theory of aging in The Selfish Gene.

“Successful genes will have ... a tendency to postpone the death of their survival machines at least until after reproduction”.

Genes tend to exert their effects at some particular stage in an animal’s life. Lethal genes, for example, may well kill an animal before it is born. A gene that causes cancer in young children will be very rare. But less lethal genes, like the ones associated with cardiovascular disease, may well spread through the population if they have their effect after their holder has successfully reproduced. The bodily decay associated with aging is then the inevitable by-product of accumulated late-acting lethal genes.

Medawar’s explanation stressed that genes that delay the effects of other, harmful genes will themselves be selected for, as will genes that hasten the effect of good genes. One of its more interesting predictions is that delaying the age of reproduction should increase lifespan, because harmful genes that would previously have acted after reproduction are now selected out before they have had a chance to reproduce. Dawkins speculates that “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.”

He then adds that he “cannot imagine that anyone would seriously want to institute such a policy”. Maybe not, in humans. In fruit flies, however, delaying reproduction over several generations increases longevity. Mice too, though less clearly.

So here's my question: do Ashkenazi Jews have their children later in life than other people?

Here is a good review of evolutionary theories of aging.