Last year, Petr Laktionov, Candidate of Biological Sciences and Senior Lecturer at NSU’s Department of Cytology and Genetics, was a winner in the Russian Science Foundation’s Presidential Program competition and awarded a 6,000,000 ruble grant. The funding was provided to support research on the role of sirtuin proteins in the regulation of resident human stem cells aging. He conducted this research together with young scientists from the NSU Natural Sciences Department Epigenetics Laboratory.
Sirtuin proteins are one of the key regulators of cellular metabolism, mitochondrial function, and chromatin remodeling. Changes in sirtuin activity in human cells and model organisms are one of the characteristic markers of aging. There is also evidence of the ability of sirtuins to influence the rate of cells aging.
Laktionov described the research,
Advances in modern healthcare have increased life expectancy and the opportunity to maintain the longevity of an active life. Aging of resident stem cells plays a significant role in age-dependent dysfunction of organs and tissues in the human body. Experimental prerequisites have also been discovered that suggest that the correction of certain manifestations of aging of resident cells can significantly slow down the aging of organs and systems. In the context of the development of regenerative medicine technologies, research into the molecular mechanisms regulating cellular aging and the development of approaches that influence its dynamics are becoming especially relevant. One of the metabolic processes key regulators associated with cellular aging are sirtuin proteins. It is noteworthy that changes in their activity are observed during aging of both human cells and model objects. This makes SIRT family proteins promising targets for research in the field of age-related diseases therapy.
The scientists have already summarized results for the first of three years of research planned for the project. This included extensive preparatory technical work, developing protocols for assessing various aging markers and their applicability for identifying stages, and constructing predictive models of cellular aging. For markers the researchers used the dynamics of changes in the expression of genes encoding key regulatory proteins, telomere length, the dynamics of the representation of markers of proliferation (cell division), DNA damage and apoptosis (genetically programmed cell death), as well as changes in chromatin structure and DNA pattern -methylation. Using machine learning algorithms, they prepared preliminary predictive models to determine the passage of LF1 cell culture based on an analysis of the dynamics of change in the representation and distribution of the histone modification H3K9me3 and the proliferation marker Ki-67.
Thanks to their preparation, the scientists were able to begin a detailed study of the age-dependent features of mesenchymal stem cell aging and the role of sirtuins in this process.
The Project leader explained,
We will study the effect of sirtuin expression modulation on the dynamics of cellular aging. The results obtained will make it possible to characterize the dynamics of activation of genome regulatory elements such as enhancers associated with the development of the genetic program of aging and rearrangements of nuclear architecture. In addition, we will study their relationship with the dynamics of chromatin architecture, age-dependent changes in the methylation pattern, and gene expression. This will provide a detailed description of the regulatory events underlying the genetic program of cellular aging, as well as to study sirtuins role in controlling these processes. From this it will be possible to characterize comprehensively the process of replicative aging at the levels of phenotypic manifestation and the underlying epigenetic regulatory mechanisms.
Author: Elena Panfilo, NSU Press Service