05 July 2010

"Longevity genes": the truth is born in disputes

Scientists have declared longevity genes a dubious discovery
Alexey Tymoshenko, GZT.RU 

An article published on July 1 in the journal Science by American researchers who found a number of signs of longevity in genes caused serious controversy. The skepticism of some scientists, including Jeffrey Barrett, a representative of the Sanger Institute in Cambridge, gave rise to a set of details – including, oddly enough, too high accuracy of the results.

In an interview with the Guardian, Barrett noted that some of the differences found by the American team meant an increase in the probability of living to a hundred years by ten times. According to the researcher, who himself is engaged in statistical analysis and genetic predisposition to diseases, this is too much. Genetic differences that change the risk of something by one and a half times are found everywhere, but ten times is unlikely.

Replacement in one letter

What exactly were the scientists from the USA looking for, who announced the discovery of genetic markers of longevity? They analyzed the DNA of a large number of people, among whom there were 1055 centenarians who had overcome the centenary milestone. The analysis revealed so-called single-nucleotide polymorphisms, places where one nucleotide is replaced by another in DNA.

Single-nucleotide polymorphisms (which, for brevity, we will designate by the English term SNP) are similar to replacing one letter in a word, and they are used to find out which variant of the gene got to a person or another organism under study.

To show the usefulness of the SNP, you can use this example – criminologists investigate the theft of a private library and find a page torn out of "War and Peace" from a suspect during a search (analogy: a DNA fragment). It looks like a fragment of a stolen book, but after all, "War and Peace" has been published many times and in huge circulations, how can we prove that this is exactly a stolen copy (i.e. we are talking not just about the human gene, but about its specific variant)?

If you do not resort to paper analysis, then additional information can help that the stolen edition either had a typo on this page, or there was an editorial footnote on it. One extra or missing character in this way will allow not only to identify the work (to understand that the DNA belongs to a person), but also to indicate a specific issue of the book (a variant of the gene).

Researchers were able to find 150 SNPs indicating differences between centenarians and the rest of the population. Further computer analysis, in turn, revealed 19 combinations of these markers, each of which significantly increased the likelihood of living to the centennial. Although geneticists are generally aware of examples of how a single error in DNA causes either ovarian cancer or premature aging of the body.

Controversy around risksBarrett's objection has already been met with a retaliatory comment by Paola Sebastiani, one of the authors of the original article and a specialist in biological statistics at Boston University.

Sebastiani noted that the phenomenon of longevity studied by them is relatively rare, in the USA, where the study was conducted, there is only one such case per 6 thousand people – but diabetes studied by Barrett is much more widespread.

The development of common diseases can be influenced by an even greater number of genetic factors than the ability to overcome the centennial milestone. And if so, then the specific weight of each "diabetes gene" will be lower than the contribution of the "longevity gene" to the overall result.

Methods

However, the unusually large contribution of genes to longevity alone does not exhaust all skeptical comments about the work of Sebastiani and co-authors. In an interview with Newsweek, two major geneticists, David Altshuyer (Broad Institute, a joint center of MIT and Harvard) and David Goldstein (Duke University) noted that the SNP search method used by researchers is far from being absolutely reliable, so differences in the DNA of centenarians and ordinary people may be due to variations in the experimental protocol.

The answer to this objection was also received, consisting in the fact that biochips of the same manufacturer were used to analyze the genetic material of both groups. Goldstein, whose words are quoted by the blog The Great Beyond (the official blog of the journal Nature), however, was not convinced – the scientist points out that the description of the experiments indicates chips from the same company, but several different versions.


Biochip is a glass plate with many microlunks,
in each of which the analyzed substance
interacts with one or another reagent.

Only a few further studies will be able to show who will be right in the end and to what extent the results of the Sebastiani group correspond to reality. In particular, doctors pin their hopes on GEHA – the European program for studying the genome of 2.5 thousand pairs of twins, whose degree of aging was assessed by doctors as less than the average for the population.

Portal "Eternal youth" http://vechnayamolodost.ru05.07.2010

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