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Objective: Adipose-derived stromal/stem cells (ASCs) have multilineage differentiation potential and functional properties, as well as applications for cell-based therapies in tissue repair and regeneration. However, there is a lack of evidence regarding the efficacy of ASCs as an antiobesity agent in aged organisms. This study aimed to clarify the effectiveness of ASCs at treating obesity using a naturally aged mouse model. Methods: Old (22 months) C57BL/6J mice with transplanted young-mice (2 months) donor ASCs were measured for weight change, biochemistry, cytokines, hormone secretion, cell senescence, lipid metabolism, and functional changes of ASCs. Results: The results indicated that old mice treated with ASCs showed antiaging and antiobesity effects such as significant loss of body and organ weight, improved stem cell plasticity, increased antioxidant capacity (superoxide dismutase and catalase), improved liver and kidney function, improved lipid metabolism, and increased hormone secretion (sex hormone-binding globulin, thyrotropin, and leptin). Treatment with ASCs decreased cell senescence and suppressed secretion of inflammatory agents (interleukin-6 and tumor necrosis factor alpha). Conclusions: Traditional drugs used in the treatment of obesity have limitations and are unsuitable for the elderly. Based on the results, the future use of ASCs as primary antiaging and antiobesity agents is suggested because of their positive effects on aged animals.

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Background Adipose-derived stem cells (ASCs) have anti-aging and anti-obesity effects in aged animals, but the underlying molecular mechanism remains unknown. Methods In the present study, we evaluated the in vivo transplantation effects of different age donor-matched ASCs on natural aging and leptin knockout mice (ob−/ob− mice). The multi-omics expression profiles of young and aged mouse donor-derived ASCs were also analyzed. Results The results revealed that ASCs from young donors induced weight and abdominal fat loss for older recipients but not for young or ob−/ob−mice. The young and aged mouse donor ASCs displayed significant phenotypic differences, contributing to the distinguished weight loss and anti-aging effects in aged mice. Conclusions Our data suggest an underlying molecular mechanism by which young-donor ASCs reduce immune cells and inflammation in aged mice via secreted immune factors. These findings point to a general anti-aging mechanism of stem cells, which may provide new insights into age-related disturbances of stem cell plasticity in healthy aging and age-related diseases.