A short walk throught the realm of DNA and genetic biochemistry today - never a dull moment here. You'll find an interesting letter at Nature on the growth of random changes (copy errors, oddities, mutations and other odds and ends) in your DNA. In science-speak, this accumulation of error is a stochastic process; somewhat random, somewhat determined by the state of your biochemistry today. The longer you live, the more genetic errors you will carry with you - and errors in your biological machinery inevitably mean that the machinery isn't working so well anymore.

The accumulation of somatic DNA damage has been implicated as a cause of ageing in [animals]. One possible mechanism by which increased DNA damage could lead to cellular degeneration and death is by stochastic deregulation of gene expression. Here we directly test for increased transcriptional noise in aged tissue by dissociating single cardiomyocytes from fresh heart samples of both young and old mice

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Although gene expression levels already varied among cardiomyocytes from young heart, this [variance] was significantly elevated at old age. We had demonstrated previously an increased load of genome rearrangements and other mutations in the heart of aged mice.

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These results underscore the stochastic nature of the ageing process, and could provide a mechanism for age-related cellular degeneration and death in tissues of multicellular organisms.

One of many mechanisms, sad to say. Researchers will need to significantly impact all of them to hit radical life extension or superlongevity - but incidental gains in fighting age-related disease along the way will not be negligible.

What we should be viewing with concern is the evidence of destruction of information: it's not unlike what happens to most magnetic storage media from the past two decades. Bits get flipped as time passes, and given long enough you lose the original data. In the case of your genome, the damage is less extensive but still worrisome.

Loss of data is much more expensive to understand and repair than other forms of damage; you're losing the very knowledge needed to guide you to the solution. It seems clear that gene therapies and related technologies are progressing rapidly towards safe, global changes and wholesale replacement of damaged portions of DNA. But what to replace in the case of pervasive, widespread random damage? It's by no means an impossible task, but it's a far more ambitious goal than curing a disease by changing a single gene.

Will it be easier if the aged patient thought to have a less damaged tissue sample cryogenically stored fifty years earlier? Maybe, or maybe bioinformatics will be at the point at which sorting out the loss of information safely will be trivial. Given the present (rapidly decreasing) cost of tissue storage, it seems almost sensible insurance against some of the possible future economics and science of healthy life extension medicine.

Technorati tags: aging, life extension, medical research

Posted by Reason at June 21, 2006 9:03 PM | TrackBack (2)