<p>Aging is a multifaceted process characterized by progressive decline in cellular and tissue function, leading to increased susceptibility to diseases. Stem cells, with their capacity for self-renewal and differentiation, play a pivotal role in maintaining tissue homeostasis and regeneration. However, stem cell function diminishes with age due to intrinsic and extrinsic factors, contributing to organismal aging. This review summarizes the mechanism of aging, role of stem cells in anti-aging and rejuvenation such as mesenchymal stromal/stem cells (MSCs), embryonic stem cells (ESCs), hematopoietic stem cells (HSCs) and induced pluripotent stem cells (iPSCs), physiological relevance of MSCs, mechanisms of stem cell aging, and impact of stem cell senescence. Challenge and future direction of stem cell application are also discussed. Understanding these mechanisms and challenges is necessary for us to develop novel stem cell therapies in anti-aging and maintaining health overall lifespan.</p>