On Genetic Variants and Human Exceptional Longevity

It is generally thought that genetic influences on natural variations in human longevity are less important than environmental factors and lifestyle choices: 25% genes versus 75% everything else are the ballpark figures often mentioned. However it is also generally thought that the importance of genetic variations increases greatly in older age: people are more likely to reach the age of 100 if they bear certain gene variants. Though it should be noted that "more likely" here is still a very low chance overall. At the present time regardless of genes most people die before reaching 90, let alone 100. This is why we need the research community to focus on better medical technology for treating and reversing degenerative aging for everyone, rather than conduct a great deal of introspection on the nature of the few percent who make it to exceptional old age.

Here is an open access paper that provides some insight into current work on the genetics of exceptional human longevity - really a matter of interest and knowledge rather than something that will lead to any sort of meaningful advance in medicine. I think that the authors are optimistic in their view that anything other than very marginal treatments can result from identifying characteristic genetic differences in centenarians. It's still the case that the vast majority of people with those differences die without living that long: the improvement in mortality rate in old age due to these longevity-associated genetic variants is not large.

Despite evidence from family studies that there is a strong genetic influence upon exceptional longevity, relatively few genetic variants have been associated with this trait. One reason could be that many genes individually have such weak effects that they cannot meet standard thresholds of genome wide significance, but as a group in specific combinations of genetic variations, they can have a strong influence. Previously we reported that such genetic signatures of 281 genetic markers associated with about 130 genes can do a relatively good job of differentiating centenarians from non-centenarians particularly if the centenarians are 106 years and older. This would support our hypothesis that the genetic influence upon exceptional longevity increases with older and older (and rarer) ages.

We investigated this list of markers using similar genetic data from 5 studies of centenarians from the USA, Europe and Japan. The results from the meta-analysis show that many of these variants are associated with survival to these extreme ages in other studies. Since many centenarians compress morbidity and disability towards the end of their lives, these results could point to biological pathways and therefore new therapeutics to increase years of healthy lives in the general population.

Link: http://www.impactaging.com/papers/v5/n8/full/100594.html


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