Wednesday, August 11, 2010

Longevity(Exceptional) - the genes have it

This recent press release has caused a world wide stir, with critics pointing out flaws in the analyses, though with the caveat that the identified flaws did not disprove the conclusions but raised questions that needed further investigation. In that link the researcher states his own research also identifies 150 specific markers in the exceptionally long lived. This more critical analysis though suggests the whole methodological approach is up the creek with one scientist quoted as saying the paper should not have been published because all the conclusions are suspect. The question is: Do we now know enough to enable people to realistically aim at extending their healthy lifespan? Not with studies like the above, but when the current centenarians were born people were only just becoming interested in the work of the quiet monk, Gregor Mendel, who pioneered modern genetics. Today we know so much more, and there is sufficient information to suggest it is possible to increase our lifespan and avoid illness. It is still a numbers game but we can play with the odds. First, some more of these genetic studies ... .

More broadly, it seems to be the case that genetic research typically makes initial finds of this or that gene, then goes on to find associations with another gene, and another one, and another one ..., which does suggest that simply deriving mathematical relationships between genetic variables is an insufficient analytic strategy. Still a very valuable strategy but perhaps we get too carried away with the implications of those analyses. A much more brute force approach, rather than subtle type of analysis, is mentioned in this instructive article from Nature magazine
But genes are only part of the story — as research on human populations has shown. Studies on twins indicate that only 25% of the variation in life span3, and half of the variation in cognitive function late in life4, can be attributed to genetic differences
This citation from the Nature article actually points to a possibility much more relevant to us. Remember, these current studies are looking at centenarians, which have always been relatively few on the ground but recently increasing in frequency, which raises questions about the "it is nearly all genetics" arguments. Current centenarians were those born in the dawn of World War 1, hardly an auspicious start to life. World War 1, the Great Depression, World War 2, the Cold War, these centenarians were certainly living in interesting times. The genetic variants that have conferred long life upon them may be confined to certain experiences of life.

A principle problem with the above argument is that longevity studies indicate the exceptionally long lived are very much confined to specific family lines the implication being that the same genetic variants conferred a longevity advantage in often quite different environments and historical periods. There may be a "cellular" approach because it is conceivable that certain very common intra-cellular processes clearly are fundamental to longevity so irrespective of whatever environmental contingencies the organism is confronted with these cellular, and also some broader physiological functions, have the ability to confer increased longevity potential across an enormous range of potential environments. It may even be a case of evolutionary convergence upon such a strategy because if an organism is going to survive hundreds of millions of years it may drive intra- cellular processes to being highly adaptable to a wide range of environments. So even in the lowly yeast there are similiar longevity related processes as seen in organisms like us. Yet surely if these genetic advantages were primarily related to cellular metabolism then these variants would have become ubiquitous by now?

The real big problem though is that studying the genomic associations of the exceptionally long lived which constitute an exceedingly small proportion of humanity is of little if any utility for helping the vast majority to extend their lives. (In time the studies will become very important, but it is one thing to know a genetic variant and another to know the implications of that variant.) The study cited by Nature, and the Nature article is a good read, I'll refer to that again later, is much more relevant in relation to health related strategies.

I'm prepared to accept that genes play a very important role in living beyond 90 years of age but suggest that applies to those generations covered under this analysis. The last 30 years have seen tremendous strides in our understanding of biological processes. It is reasonable to assume we are approaching the time when prudent individuals through disciplined regulation of their lifestyle can reasonably expect to live not only beyond 90 but do so with vigour and fun and productivity.

Coming back to that Nature citation, I referenced an earlier abstract from that series of twin studies and the relationship holds across set of studies, approximately 25% of longevity can be related to genes. Just what is meant by 25%? Are all genes of equal weighting in this 25%? It is almost a complete reversal of the claim made by these recent publicised papers,  the clear implication being that there is a great deal people can do to increase their longevity chances. Nor do we need experts or magic potions: the primary advice remains in play: no bad habits, regular exercise, eat well, sleep well, be happy. For the more seriously minded there are other strategies to consider, from supplementation to pollutant exposure, each person has to work that out for themselves.

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