The building block for liver fitness in aging

The structure of the liver changes with age. Shown here is a histological image of small hepatocytes (left) and hepatocytes (right). Credit: Max Planck Institute of Gerontology

The liver can regenerate even in old age and remain surprisingly fit, even though the chromatin in its cells undergoes significant remodeling due to epigenetic changes, researchers from the Max Planck Institute for Biology of Aging in Cologne have now discovered. One possible reason for the shift in minor consequences could be the mechanism the researchers now describe in the journal molecular systems biology.

Changes in epigenetics are considered to be the cause of aging processes. Epigenetics describes changes in genetic information which do not change the gene sequence itself, but affect their activity. Among other things, this can be regulated by the accessibility of proteins to DNA as part of chromatin. In this study, researchers observed in liver cells The DNA of liver cells becomes less firm with age. This makes the DNA more accessible for the production of the messenger RNA molecule. “If DNA is easily accessible, we should also see greater amounts of RNA being produced. But that has never been the case,” says Peter Tessars, study leader.

Shorter break in DNA

Researchers already have a possible explanation for this. They found that RNA polymerase, a protein that binds to DNA and then produces RNA, falls off the DNA more quickly in aging liver cells than in young cells. This lower stability means that despite the increased accessibility to DNA, there is no net increase in RNA production, which maintains homeostasis within the cell.

“We think we have discovered a new pathway in cells that compensates for age dependence epigenetic changes. This may be one reason why the liver can continue to function for so long. Whether a similar mechanism interferes with epigenetic changes in other tissues remains to be explored in the future. There, however, we also observe very different genetic changes during aging,” says Tessars.

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more information:
Mihaela Bozukova et al, Aging is associated with increased chromatin accessibility and reduced transient polymerase arrest in the liver, molecular systems biology (2022). DOI: 10.15252 / msb.202211002

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