03 September 2013

Aging and epigenetics: new data

One of the mechanisms used by the cell to prevent malignancy is the so–called physiological aging - the irreversible cessation of division. This mechanism is also associated with normal aging of the body. Studying the basics of physiological cell aging should help specialists understand the mechanisms of development of age-related diseases, including cancer.

Researchers from the University of Pennsylvania, working under the guidance of Professor Shelley Berger, have established that a certain role in the physiological aging of the cell belongs to epigenetic factors affecting chromatin – the structure that ensures the ordering of genetic material in the nucleus.

They compared the nature of epigenetic tags scattered throughout the genome of two populations of lung cells: a population acting as a control, whose cells were just beginning to proliferate, and a population whose cells had already stopped dividing and entered the phase of physiological aging.

The results of the analysis showed that the deletion of the lamin B1 nuclear protein occurring during physiological aging is accompanied by large-scale changes in gene expression, as well as chromatin structure, affecting approximately 30% of the genome.

Lamin B1 is part of the lamina or nuclear plate, a structure lining the inner surface of the nuclear envelope and ensuring the maintenance of the shape of the nucleus, as well as participating in DNA replication by providing or closing access to certain regions of the genome. In case of suppression of gene activity, lamina proteins form strong bonds with chromatin proteins.

The authors also demonstrated that a deliberate decrease in the content of lamin B1 in dividing cells triggers premature physiological aging, characterized by characteristic chromatin changes. Based on this, they came to the conclusion that it is the loss of this protein that causes changes in the structure of chromatin, which contributes to cell aging.

Comparison of the genomes of cells of children with hereditary Getchinson-Guilford syndrome (progeria), characterized by premature aging, with the genomes of cells of their healthy parents revealed the presence of so-called "mesa structures" in the genomes of children marking chromatin in the DNA regions encoding lamin B1 as "accessible". This label, which is not detectable in the cells of healthy parents, is a sign of cell aging.

According to the authors, the data obtained demonstrate a pronounced reorganization of chromatin in the process of physiological aging of the cell, affecting gene expression, the rate of aging of the body and the risk of cancer. They also point out that a key link in this process is a decrease in the activity of lamin B1. Berger adds that since the risk of developing many diseases, including cancer, increases exponentially as the body ages, the ultimate goal of this study is to decipher the mechanisms of the relationship between the mechanisms underlying aging and age-related diseases.

Article by Parisha P. Shah et al. Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape published in the journal Genes & Development.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Pennsylvania School of Medicine:
Balancing Act: Cell Senescence, Aging Related to Epigenetic Changes.


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