Aging impairs beige adipocyte differentiation of mesenchymal stem cells via the reduced expression of Sirtuin 1
| Autor: | Amin Firman Zulkifli, Toshiharu Yamashita, Osamu Ohneda, Yuji Hiramatsu, Vuong Cat Khanh, Chiho Tokunaga |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Senescence Cyclin-Dependent Kinase Inhibitor p21 Aging SIRT3 Biophysics Adipose tissue Biochemistry 03 medical and health sciences 0302 clinical medicine Sirtuin 1 Sirtuin 3 Humans Adipocytes Beige Progenitor cell Molecular Biology Cellular Senescence Aged Aged 80 and over biology Mesenchymal stem cell Infant Newborn Infant Cell Differentiation Mesenchymal Stem Cells Cell Biology Tissue Donors Cell biology 030104 developmental biology 030220 oncology & carcinogenesis Sirtuin biology.protein MYF5 Tumor Suppressor Protein p53 Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 500(3) |
| ISSN: | 1090-2104 |
| Popis: | In the body, different types of adipose tissue perform different functions, with brown and beige adipose tissues playing unique roles in dissipating energy. Throughout life, adipocytes are regenerated from progenitors, and this process is impaired by aging. One of the progenitors of adipocytes are mesenchymal stem cells (MSCs), which have recently become a promising tool for stem cell therapy. However, whether or not aging impairs the brown/beige adipocyte differentiation of adipose tissue-derived MSCs (AT-MSCs) remains unclear. In the present study, we isolated AT-MSCs from two different age groups of donors (infants and elderly subjects) and examined the effects of aging on the AT-MSC brown/beige adipocyte differentiation ability. We found that none of the AT-MSCs expressed Myf5, which indicated the beige (not brown) differentiation ability of cells. Of note, an inverse correlation was noted between the beige adipocyte differentiation ability and age, with AT-MSCs derived from elderly donors showed the most severely reduced function due to induced cellular senescence. The impaired expression of Sirtuin 1 (Sirt1) and Sirt3 proved to be responsible for the induction of senescence in elderly AT-MSCs; however, only Sirt1 was directly involved in the regulation of beige adipocyte differentiation. The overexpression of Sirt1 impaired the p53/p21 pathway, thereby preventing elderly AT-MSCs from entering senescence and restoring the beige differentiation ability. Thus, our study represents the important role of Sirt1 and senescence in the regulation of beige adipocyte differentiation during aging. |
| Databáze: | OpenAIRE |
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