Open Access5‐Azacytydine and resveratrol reverse senescence and ageing of adipose stem cells via modulation of mitochondrial dynamics and autophagy
Author(s) -
Kornicka Katarzyna,
SzłapkaKosarzewska Jolanta,
Śmieszek Agnieszka,
Marycz Krzysztof
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13914
Subject(s) - autophagy , resveratrol , microbiology and biotechnology , senescence , biology , stem cell , mitochondrion , apoptosis , adipose tissue , epigenetics , population , reactive oxygen species , fis1 , flow cytometry , programmed cell death , mitochondrial dna , mitochondrial fusion , immunology , pharmacology , medicine , biochemistry , gene , environmental health
Obesity and endocrine disorders have become prevalent issues in the field of both human and veterinary medicine. Equine metabolic syndrome is a complex disorder involving alternation in metabolism and chronic systemic inflammation. It has been shown that unfavourable microenvironment of inflamed adipose tissue negatively affects adipose stem cell population ( ASC ) residing within, markedly limiting their therapeutic potential. ASC s EMS are characterized by increased senescence apoptosis, excessive accumulation of reactive oxygen species ( ROS ), mitochondria deterioration and “autophagic flux.” The aim of the present study was to evaluate whether treatment of ASC s EMS with a combination of 5‐azacytydine ( AZA ) and resveratrol ( RES ) would reverse aged phenotype of these cells. For this reason, we performed the following analyzes: molecular biology ( RT ‐ PCR ), microscopic (immunofluorescence, TEM ) and flow cytometry ( JC ‐1, ROS , Ki67). We evaluated the mitochondrial status, dynamics and clearance as well as autophagic pathways. Furthermore, we investigated epigenetic alternations in treated cells by measuring the expression of TET genes and analysis of DNA methylation status. We have demonstrated that AZA / RES treatment of ASC s EMS is able to rejuvenate these cells by modulating mitochondrial dynamics, in particular by promoting mitochondrial fusion over fission. After AZA / RES treatment, ASC s EMS were characterized by increased proliferation rate, decreased apoptosis and senescence and lower ROS accumulation. Our findings offer a novel approach and potential targets for the beneficial effects of AZA / RES in ameliorating stem cell dysfunctions.