Random Genetic Mutations, Mishaps, Copy Errors and Other Oddities

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


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.


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.

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This result elevates mathematician and critic William Empson's remarkable villanelle "Missing Dates" from poetic conceit to near scientific prognostication.

From the last two stanzas:

Not to have fire is to be a skin that shrills.
The complete fire is death. From partial fires
The waste remains, the waste remains and kills.

It is the poems you have lost, the ills
From missing dates, at which the heart expires.
Slowly the poison the whole blood stream fills.
The waste remains, the waste remains and kills.

Posted by: Nobody at June 24th, 2006 6:51 AM

By sequencing an individual genome by using multiple samples from the same person, it should be possible to extrapolate the original DNA by finding the mode of the nucleotides of the genomic sequences. It would be like recompiling an original document that was written 1000 years ago by looking at different copies of the document that were all damaged or altered in multiple ways. The original information will more likely than not be the mode of the letters at each position of the document. In this way, a person's original DNA information may be retrieved regardless of age. However, how to use this information is a much harder question to answer.

Posted by: Mike at January 25th, 2016 10:38 AM
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