The gene of a happy old age

Geneticists have figured out how to find longevity genes in people.
However, they did not find very much, and there are objective reasons for that

Alexey Aleksenko, "Snob"

Since there are long–lived dynasties in the world – take the current English queen and her mother, for example - it makes sense to look for natural prerequisites for this. Including, perhaps, genetic ones. Now, when human genomes are deciphered by literally thousands, it's easier to do this: first we accumulate data on all sorts of individual features of genes (that is, mutations), and then we find out how long a person has lived with such and such a set of mutations. Then statistical analysis, and the thing is in the hat: we will find out which gene variants correlate with longevity.

It was a joke, of course. Well, how do you imagine it: scientists stock up on a genetic database, and then start calling those who lit up in it? "Well, are you still alive? Oh, and for some reason this phone does not answer ..." Yes, even such a stupid way is not feasible: most clients of firms doing genetic analysis stipulate the condition of anonymity.

Dear reader, you can now take a minute's pause and try to figure out how to identify the genes of longevity without waiting for everyone to die – by way of a laborious, but one-time study. And then check if you guessed right.

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American geneticist Ahamanesh Mostafavi from Columbia University and his international team came up with the following method. Look: if we are looking for mutations, because of which people do not live to old age, then it is unlikely that we will find these mutations in the very old. Fortunately, the databases have information about the age of those who provided the material for genetic analysis. And it should be expected that the relative proportion of such mutations will decrease markedly with increasing age of carriers. It is a little less obvious (although in fact it is a consequence of exactly the same reasoning) that older subjects will have a slightly higher proportion of mutations that determine longevity than the average for the sample.

Then it's a matter of technique: to analyze the genetic data of 215,000 people from the largest databases in the UK and the USA. Those genetic variants, the frequency of which statistically significantly varies depending on age, are what we need. At the output we get the genes of a happy old age and the genes of premature death, do not be taken in vain.

The team of researchers tested more than 8 million mutations (geneticists often call them "single nucleotide polymorphisms, or SNPs, or in Russian "snips"). And some disappointment awaited them: the frequency of SNP somehow almost did not change by age group, and if it did, it was inconclusive. Out of eight million points in the genome, the statistical sieve caught only two SNPs. And these were not the genes of a happy old age – on the contrary, they were genes that do not seem to allow you to live to this old age.

The first such gene is APOE, which was already known to be involved in the development of Alzheimer's disease. In women over 70 years of age, the mutation in this gene was much less common than the sample average. The second gene is a little more interesting: CHRNA3 correlates with a strong dependence on nicotine in men. The frequency of this gene began to decrease markedly – again in men – already in the fifth decade.

A note in parentheses: dear fighters against smoking, we would like to draw your attention to the fact that these data do not say anything at all that smoking a lot is harmful. Perhaps the CHRNA3 gene (or rather, a certain mutation in it) encourages its carrier to worry about trifles, or, for example, to cheer for the country rolling into the abyss, or to turn pale with anger at the sight of injustice. From this, of course, it is no wonder to fade out like a candle in the prime of life, and from this the hand reaches for cigarettes every five minutes, but these two consequences may not be related to each other. So the harm of smoking is still a hypothesis. Although, of course, it is very plausible, what's there to argue about.

A married couple is more likely to have children if elderly relatives help to raise them. Thus, the longer these relatives live, the more descendants they have, that's the selection mechanism for you

Only two genes per eight million is very, very small, and even suspiciously small – we will return to this a little later. In the meantime, we note that although there are almost no individual "longevity mutations" left in the statistical sieve, but their ensembles, that is, combinations, remain. For example, combinations of polymorphisms correlating with a predisposition to asthma, obesity and high cholesterol levels noticeably disappeared with the age of the carrier, because carriers of such combinations obviously did not live to old age. There is nothing surprising here: he was ill a lot, looked bad, died early. These, of course, are not "life expectancy genes", but simply genes that spoil this very life.

And what about the genes that lengthen life? With those that are more common among centenarians than among young people? No individual genes were found, but combinations were found, and quite curious. Their presence, in addition to the age of the carriers, correlates with such a curious property as delayed reproductive maturity and late childbearing. The fact that these features of human destiny are somehow connected with longevity was known before, but it was explained by social reasons. If you do not trade on the stock exchange and do not work in the office 12 hours a day, you most likely have a lot of free time, little ability to self–control and very, very little money - it is not surprising if you get knocked up early with such a set of qualities, and then die early. The data from this study shows that everything is more complicated, and this story really has a genetic background.

But back to the main thing. The main thing is this: there are suspiciously few mutations correlating with life expectancy. According to the authors, this is not for nothing. The authors in their article make a bold assumption: perhaps there are so few life-shortening mutations because natural selection sweeps them out?

At the very first glance, this is natural, but already at the second – it contradicts everything that the science of gerontology has stood on for decades. This science teaches that selection does not care what happens to an individual after she gives offspring and brings him up to reproductive maturity. When your child enters the "age of consent" and moves into a rented one-bedroom apartment, natural selection says goodbye to you forever.

But what if it's not? One of the possible ways in which selection can overtake you in old age, anthropologists have suggested for a long time: this is the "grandmother effect". Its essence is that a married couple is more willing to have children if elderly relatives help to raise them. Thus, the longer these relatives live, the more descendants they have, that's the selection mechanism for you.

But if this mechanism really works as effectively as the results of this study suggest – almost completely sweeping out of the population everything that can shorten the human century – it means that selection has already driven our life expectancy right under the biologically possible maximum. Therefore, all the pleasant conversations of gerontologists that supposedly nothing prevents us from living for two hundred years have no basis. It's sad, of course, but science has not promised to always please us in everything. But she promised to reveal to us how it really is, which is also a lot.

In conclusion, I should probably say that this study will certainly be refined, and very soon we will find out where the selection really leads us. The databases of genetic data are growing and swelling literally every day. In fifty years, they will already have data covering three generations of people. Then it will be possible to see the dynamics of human evolution, without resorting to subterfuge, but simply comparing "was" and "became".

You and I probably won't live to see it. Unless, of course, the recipe for a long life is developed literally tomorrow – and then such studies will completely lose all practical interest. But so far, for our taste, they are very exciting.

Portal "Eternal youth" http://vechnayamolodost.ru  18.09.2017