期刊
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
卷 69, 期 1, 页码 13-24出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glt043
关键词
Adipogenesis; Adipokine; Adipose-derived stromal/progenitor cells; Aging; C/EBP alpha; Senescence; Proliferation; PPAR gamma 2; p16Ink4A; p53; p21Cip1; Retinoblastoma protein
资金
- Austrian Academy of Sciences
- University of Innsbruck
We demonstrate that adipose-derived stromal/progenitor cells isolated from abdominal subcutaneous fat pads of adult donors successively enter replicative senescence after long-term cultivation. This is characterized by enlarged cell size, flattened morphology, and upregulated senescence-associated beta-galactosidase activity. Moreover, the senescence-associated cyclin-dependent kinase inhibitors p16(Ink4A) and p21(Cip1) were induced correlating with activation of the G1/S cell cycle inhibitor retinoblastoma protein and terminal proliferation arrest. The number of cells in the adipose-derived stromal/progenitor cell population with high adipogenic capacity declined inversely with the increase of senescent cells. Adipogenic hormone cocktail induced expression of the adipogenic key regulators peroxisome proliferator-activated receptor-gamma 2 and CCAAT/enhancer-binding protein alpha was significantly reduced in senescent adipose-derived stromal/progenitor cells. Furthermore, the expression of the adipogenic differentiation genes fatty acid binding protein-4, adiponectin, and leptin and the formation of fat droplets were impaired. We conclude cellular senescence contributes to dysfunctions in adipose-derived stromal/progenitor cell replication, adipogenesis, triglyceride storage, and adipokine secretion.
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