Ageless liver
The secret of liver longevity lies in the balance between DNA and the enzymes interacting with it
Anna Novikovskaya, Naked Science
The liver remains remarkably healthy even in the elderly and regenerates perfectly, although the DNA in its cells undergoes significant rearrangements due to epigenetic changes. For a long time, scientists could not understand why changes that lead to noticeable decrepitude in other organs do not have a significant effect on the liver. Now it looks like they've managed to find the answer.
After studying the changes that occur with liver cells as they age, the authors of the new work found that with age, the DNA in the cell nuclei becomes less twisted, and this facilitates access to it by various enzymes. It would seem that in such a situation, more mRNAs should be produced in the cells of elderly people — molecules that "read" information from the DNA molecule and serve as a matrix for protein synthesis — which will inevitably lead to depletion of cellular resources.
However, this does not happen due to the maintained balance between DNA unwinding and a decrease in the activity of the main enzyme responsible for RNA synthesis, RNA polymerase. It turned out that in the cells of the elderly, this enzyme forms less stable complexes and more often falls away from the DNA molecule without completing the construction of the RNA molecule.
As a result, the "imperfection" is broken down by other enzymes into components, and protein synthesis does not begin. This keeps the cell's resources virtually intact and allows the liver to maintain activity for longer.
Liver cells of a young (left) and elderly (right) person. Figure from the press release of the Max Planck Institute for Biology of Aging A building block for liver fitness in old age - VM.
Thus, liver cells compensate for epigenetic DNA changes that occur with age. Now scientists have to find out whether similar DNA changes occur in other organs. And if so, is it possible to launch such a compensatory mechanism in them to maintain their health and longevity?
The study was published in the journal Molecular Systems Biology (Bozukova et al., Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver).
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