Unstable DNA in neurons: counter of the life span and a driver of evolution

Abstract

The data on postmitotic instability of neuronal DNA, which have been reported in the last decade, are changing the theoretical landscape not only of neuroscience, but more broadly, of biology. A. M. Olovnikov suggested in 2003 that it is the DNA of neurons that can be the “initial substrate of aging”. The current data significantly increases the likelihood of this hypothesis. How does neuronal DNA accumulate damage, in what regions of the genome, what factors contribute to its accumulation, and how can they be associated with aging and the life span? These questions will be considered in the review. In addition, instability of the neuronal DNA had apparently been accompanied by a search for various ways to reduce the biological costs of brain function in Metazoan evolution. Phenomena such as sleep, an increase in the number of neurons in the vertebrate brain evolution, adult neurogenesis, distributed neuronal activity, somatic polyploidy, RNA editing in cephalopods can be reconsidered in the light of “DNA plasticity-instability trade-off” in neurons. The topic is of obvious importance not only for fundamental neuroscience, but also for translational medicine.