What is the role of transcription error in aging?

Ed Park, MD News 1 Comment

My friend and proofreader, Jerome, took to task to my New Year’s Blog about aging being impacted by repeated copying of the genome. Briefly, although the shortening of telomeres is undoubtedly related to mutations, he suggests that the actual information DNA is not appreciably degraded.

If we assume 3 billion base pairs per human cell, 1/100,000 transcription errors, but a high rate of intra-transcriptional proofreading, we get that figure down to about 0.3 mutations (wrong letter substitution) per cell division.


We don’t know if those errors are evenly distributed between daughters and over time so one could argue that is acceptably low or perhaps over gazillions of random mutations, the accumulation is significant.  A comparison of preserved cord blood with children and young adults with respect to their genetic integrity could help answer this question but sadly, this is an area of utmost importance that has been neglected.

Scientists should already have determined out of the 3 Billion base pairs in a human genome, what percent of the original source code has changed per year. Chances are factors such as stress, sleep, telomerase activity and other DNA copy, repair, and error-correction pathways have a role but that over time, the integrity is subject to drift which accelerates with the depletion of relatively intact aboriginal stem cells.

Perhaps Jerome is right to suggest most of the phenotypic phenomena of aging are not in the DNA but in the epigenetic modifications.  Somehow I think that it is probably both, except in the germ line cells (the eggs and sperm) that must maintain a relatively higher rate of error correction for the survival of the species. One of the most interesting studies of TA-65 in mice showed that telomerase activity could reverse aging suggesting that telomeres may not only be timebombs, but that their DNA and TERRA epigenetic modifications could act as a form of reversible timekeeper for the behavior of the cell as well.

Comments 1

  1. Area for consideration: How does a totally youthful embryo/baby result from parental DNA that has been duplicated for eons of time with virtually endless prior duplications to culminate in yet another atomic software copy accompanied with epigenetic modifications? Some of the DNA at conception has been copied since the first functional cell or even partial living cell entity. The master copy DNA at conception is certainly nothing new yet it does produce a totally youthful progeny irregardless of the species, plant or animal. That ability must exist in that atomic/molecular prescript(software). It therefore could be replicated or else it would not occur period, let alone so prolifically and “naturally” thousands of times per day. And without intelligent intervention or support.

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