Another aging mechanism has been identified
The results of a study by scientists from the Salk Institute of Biological Research and the Chinese Academy of Sciences, working under the leadership of Juan Carlos Izpisua Belmonte, indicate that the aging process is closely interrelated with the violation of the integrity of heterochromatin – densely packed sections of cellular DNA.
As part of their work, the authors studied the cause of the development of Werner syndrome, or adult progeria, a hereditary disease that causes premature aging and early development of age–related diseases such as cataracts, type 2 diabetes mellitus, atherosclerosis and cancer. The life expectancy of patients with this disease is, as a rule, 40-50 years.
Werner syndrome is caused by a mutation of the WRN gene, the protein product of which is an enzyme that supports the structure and integrity of human DNA. Defects in this protein lead to violations of the mechanisms of replication and repair of DNA damage, as well as the expression of genes considered responsible for premature aging. However, it was still unclear how the mutant protein interferes with these important intracellular processes.
On the left, normal human cells are depicted, and on the right, modified cells that are a model of Werner syndrome, showing signs of aging, including abnormally large sizes.
To clarify this issue, the authors created a cellular model of Werner syndrome by removing the WRN gene from the genome of human stem cells. A detailed study of such prematurely aging cells showed that the absence of the WRN gene led to disorganization of the structure of heterochromatin – tightly twisted chains of nuclear DNA. Further experiments have shown that the protein product of this gene directly interacts with molecular structures that ensure the stability of heterochromatin.
The dense twisting of DNA chains in the heterochromatin composition provides control over the activity of genes and control of a complex complex of intracellular molecular mechanisms. Chemical markers, or epigenetic labels, regulating its structure are attached to the outer surface of heterochromatin. Rearrangements of these chemical labels can alter the structure of heterochromatin, suppressing or activating the expression of certain genes.
According to Ispizua Belmonte, the revealed relationship explains how a mutation in one gene leads to a global disruption of cellular processes caused by failures in the epigenetic regulation of gene activity. In a broader sense, this indicates that the accumulation of disorders of the structure of heterochromatin may be the main cause of cellular aging. This leads to the question of the possibility of restoring these disorders to prevent or cure age-related diseases and age-related extinction of body functions.
The authors also note that there is still a lot of scrupulous work to be done before a full understanding of the role of heterochromatin structural disorders in aging, including its interaction with other cellular processes involved in aging, such as telomere shortening.
Article by Weiqi Zhang et al. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging published in the journal Science.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Salk Institute for Biological Studies:
Scientists discover key driver of human aging.
07.05.2015