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Replicative Senescence and Expression of Autophagy Genes in Mesenchymal Stromal Cells

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Abstract

Cell senescence leads to a number of changes in the properties of mesenchymal stromal cells (MSCs). In particular, the number of damaged structures is increased producing negative effect on intracellular processes. Elimination of the damaged molecules and organelles occurs via autophagy that can be important in the context of aging. Cultivation under low oxygen level can be used as an approach for enhancement of MSC therapeutic properties and “slowing down” cell senescence. The goal of this work was to study some morphological and functional characteristics and expression of autophagy-associated genes during replicative senescence of MSCs under different oxygen concentration. The study revealed changes in the regulation of autophagy at the transcriptional level. Upregulation of the expression of autophagosome membrane growth genes ATG9A and ULK1, of the autophagosome maturation genes CTSD, CLN3, GAA, and GABARAPL1, of the autophagy regulation genes TP53, TGFB1, BCL2L1, FADD, and HTT was shown. These changes were accompanied by downregulation of IGF1 and TGM2 expression. Increase of the lysosomal compartment volume was observed in the senescent MSCs that also indicated increase of their degradation activity. The number of lysosomes was decreased following prolonged cultivation under low oxygen concentration (5%). The replicative senescence of MSCs under conditions of different oxygen levels led to the similar modifications in the expression of the autophagy-associated genes.

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Abbreviations

FSC-A:

forward scatter area

MSCs:

mesenchymal stromal/stem cells

ROS:

reactive oxygen species

SA-β-Gal:

senescence-associated β-galactosidase

SSC-A:

side scatter area

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Funding

The work was financially supported by the Russian Foundation for Basic Research (project no. 19-015-00150-A).

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  1. Institute of Biomedical Problems (IBMP), Russian Academy of Sciences, 123007, Moscow, Russia

    A. Y. Ratushnyy, Y. V. Rudimova & L. B. Buravkova

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  1. A. Y. Ratushnyy
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Correspondence to A. Y. Ratushnyy.

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Ratushnyy, A.Y., Rudimova, Y.V. & Buravkova, L.B. Replicative Senescence and Expression of Autophagy Genes in Mesenchymal Stromal Cells. Biochemistry Moscow 85, 1169–1177 (2020). https://doi.org/10.1134/S0006297920100053

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