Adipose‐derived stem cells regulate metabolic homeostasis and delay aging by promoting mitophagy

Abstract Tissues undergo a process of degeneration as the body ages. Mesenchymal stem cells (MSCs) have been found to have major potential in delaying the aging process in tissues and organs. However, the mechanism underlying the anti‐aging effects of MSC is not clear which limits clinical applications. In this study, we used adipose‐derived mesenchymal stem cells (ADSCs) to perform anti‐aging treatments on senescent cells and progeroid animal models. Following intervention with ADSCs, replicative senescence was delayed and metabolic homeostasis was transformed from catabolism to anabolism. Metabolomic tests were used to analyze different metabolites. We found that ADSCs acted to accelerate mitophagy which eliminated intracellular ROS and improved the quality of mitochondria. These processes acted to regulate the cellular metabolic homeostasis and ultimately delayed the process of aging. Allogeneic stem cell therapy in a Progeria animal model (DNA polymerase gamma (POLG) knockin, mitochondrial dysfunction) also showed that ADSC therapy can improve alopecia and kyphosis by promoting mitophagy. Our research confirms for the first time that allogeneic stem cell therapy can improve aging‐related symbols and phenotypes through mitochondrial quality control. These results are highly significant for the future applications of stem cells in aging‐related diseases.