Regulation of adipose tissue inflammation in aging by mesenchymal stem cells
IRN AP09058312
Introduction: It is known that, with aging, there is a change in fat distribution, including a relative increase in intra-abdominal fat and ectopic fat deposition, which is often accompanied by obesity. It is important to note that obesity with aging accelerates the aging process and the development of such chronic diseases as ischemic heart disease, hypertension, type 2 diabetes mellitus (DM2), osteoarthritis, cataracts, etc. In the last decade, it has been shown that slowly progressive inflammation of adipose tissue is one of the key pathogenetic factors in obesity and aging. One of the important endogenous regulators of inflammation in tissues is mesenchymal stem cells (MSC), due to their powerful secretory activity. However, with aging, the secretory activity of MSCs changes and becomes pro-inflammatory. One of the methods for normalizing the activity of MSC functioning is the transplantation of MSCs that secrete anti-inflammatory cytokines. The most effective operation can be performed by introducing autologous MSCs. In our previous studies, it was shown that the Cdc42 protein is an important regulator of aging of MSCs and the activity of Cdc42 had increased the level of senescent MSCs in tissues isolated from adipose tissue of aging animals. In a number of works, including this previous study, it was shown that inhibition of Cdc42 activity improves the secretion of MSCs and partially rejuvenates cells. We suggest that the transplantation of MSCs, which undergoes inhibition of Cdc42 activity into animals with inflammaging of adipose tissue, may be a method of therapy for senile obesity.
Goal: is to study of the regulation of inflammaging of adipose tissue by mesenchymal stem cells after inhibition of Cdc42
Expected results:
The activity of Cdc42 in murine mesenchymal stem cells from adipose tissue (ADMSCs) of aged obese mice will be studied; The effects of inhibition of Cdc42 on the secretome of aged murine adipose-derived mesenchymal stem cells (ADMSCs) will be studied; The therapeutic potential of ADMSCs after Cdc42 inhibition on adipose tissue inflammaging in vivo will be evaluated; at least 2 (two) articles and (or) reviews in peer-reviewed scientific publications on the scientific direction of the project, included in 1 (first), 2 (second) or 3 (third) quartiles in the Web of Science database will be published (presumable journals: Oxidative medicine and cellular longevity (CiteScore 2019 -7.3, percentile – 83, journal H Index -79, Quartiles –Q2 (Aging), IF-4.58, https://www.scimagojr.com/journalsearch.php?q=19700175026&tip=sid; Stem Cells International (CiteScore2019 -7.200, H- Index -55,IF- 3.869, )https://www.scimagojr.com/journalsearch.php?q=19900191989&tip=sid&clean=0); - at least 1 (one) article or review in a peer-reviewed foreign or domestic publication recommended by CCESME MOS RK;
Current results:
In 2021, the activity of Cdc42 in murine mesenchymal stem cells from adipose tissue (ADMSCs) of aged obese mice was studied. Inflammatory adipose tissue obesity has been shown to increase the activity of Cdc42 in adipose tissue mesenchymal stem cells, which in turn accelerates cell aging.
Research group:
Publications
Список публикации за 2021 год: Umbayev B., Safarova Y., Yermekova A., Saliev T. (2021)Calorie Restriction Mimetics and Adult Stem Cells. In: Rattan S.I.S., Kaur G. (eds) Nutrition, Food and Diet in Ageing and Longevity. Healthy Ageing and Longevity, vol 14. Springer, Cham. https://doi.org/10.1007/978-3-030-83017-5_25.