Cinnamaldehyde Delays the Senescence of Mesenchymal Stem Cells by Maintaining Mitochondrial Homeostasis

Jiameng Li, Pengqian Wang, Danli Hao, Ran Xie, Qi Song, Chun Li, Hairu Huo, Feng Sui

Article ID: 8127
Vol 38, Issue 6, 2024
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20243806.395
Received: 5 April 2024; Accepted: 5 April 2024; Available online: 20 June 2024; Issue release: 20 June 2024


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Abstract

Background: Stem cell exhaustion is a primary factor in human aging. The ability to delay aging by maintaining the steady state of stem cells has emerged as a crucial area of concern. However, the regulatory impact of Cinnamaldehyde (Cina) on stem cell senescence remains unknown. Therefore, this study aimed to elucidate the regulatory effect of Cina on the senescence of mesenchymal stem cells (MSCs). Methods: Physiological cell senescence model was established by cell subculture. Cell counting kit-8 (CCK-8) proliferation assay, continuous doubling experiment, Ki67 staining, and cell cycle assay were used to examine the impact of Cina on the proliferation of MSCs. Senescence-associated β-galactosidase (SA-β-gal) staining was used to evaluate the senescence of MSCs. Histone H3 trimethylated at lysine 9 (H3K9me3) staining was used to assess the stability of MSCs chromatin. Osteogenic and adipogenic induction tests were used to evaluate the differentiation potential of MSCs, and 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1) staining was used to evaluate the mitochondrial membrane potential. Glutathione (GSH) assay was used to assess the intracellular redox status. Adenosine triphosphate (ATP) detection and the Seahorse test were used to detect the energy metabolism of cells. Additionally, real-time quantitative PCR (RT-PCR) was used to quantify the indexes associated with senescence, proliferation, and differentiation of MSCs. Moreover, changes in MSCs senescence-related signaling pathways were analyzed using transcriptome. Results: Cina significantly promoted the proliferation of MSCs, maintained their proliferation rate in prolonged exposure, and delayed their senescence (p < 0.05). Cina reduced the number of SA-β-gal posit mycoplasmaive cells, decreased the levels of senescence markers such as cyclin dependent kinase inhibitor 2A (P16), cyclin dependent kinase inhibitor 1A (P21), interleukin 6 (IL-6), and IL-8, and increased the level of Recombinant lamin B1 (LMNB1). Furthermore, Cina treatment increased the expression of H3K9me3, increased the number of Ki67 positive cells, and reversed cell cycle arrest (p < 0.05). Additionally, Cina upregulated the expression of pluripotency-related genes and downregulated senescence-related signaling pathways, such as P53 and RAS-associated protein 1 (RAP1). In osteogenic and adipogenic experiments, Cina was found to promote the differentiation of MSCs (p < 0.05). Furthermore, we observed that Cina substantially protected mitochondrial membrane potential from damage caused by passage replication, maintained intracellular redox balance, and promoted mitochondrial ATP production (p < 0.05). Conclusions: This study indicates that Cinnamaldehyde (Cina) can delay the senescence of MSCs by maintaining mitochondrial homeostasis, suggesting that Cina has a potential anti-aging effect.


Keywords

cinnamaldehyde;mesenchymal stem cells;aging;mitochondrial homeostasis


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