Mesenchymal stem cells (MSCs) play a crucial role in tissue regeneration and maintenance, but their functionality declines with age, affecting regenerative capacity. Aging leads to reduced stem cell function, impairing tissue homeostasis and repair. MSCs are multipotent cells found in various tissues, capable of differentiating into multiple cell types. They reside in complex networks, influencing hematopoietic cell differentiation and maintaining blood vessel integrity. However, aging causes MSCs to lose self-renewal ability and differentiation potential, impacting their therapeutic use. Aging in MSCs is influenced by factors such as oxidative stress, inflammation, and telomere attrition. These changes can lead to impaired osteogenic potential and increased adipogenic differentiation. Inflammatory cues disrupt regulatory networks necessary for tissue regeneration. MSCs from older individuals show altered differentiation capabilities, with reduced osteogenic potential and increased adipogenic potential. These changes are linked to systemic inflammation and age-related diseases. MSCs used in regenerative medicine face challenges due to their aging process. Long-term ex-vivo cultivation can lead to senescence, reducing their efficacy. Current methods for MSC expansion and characterization are limited, and there is a need for better understanding of MSC aging to improve clinical applications. Research is ongoing to optimize ex-vivo culture conditions and develop reliable biomarkers for MSC aging. Understanding MSC aging is essential for selecting appropriate donors and ensuring the safety and effectiveness of MSC-based therapies. Further studies are needed to identify specific pathways involved in MSC activation and to develop innovative approaches for clinical translation.Mesenchymal stem cells (MSCs) play a crucial role in tissue regeneration and maintenance, but their functionality declines with age, affecting regenerative capacity. Aging leads to reduced stem cell function, impairing tissue homeostasis and repair. MSCs are multipotent cells found in various tissues, capable of differentiating into multiple cell types. They reside in complex networks, influencing hematopoietic cell differentiation and maintaining blood vessel integrity. However, aging causes MSCs to lose self-renewal ability and differentiation potential, impacting their therapeutic use. Aging in MSCs is influenced by factors such as oxidative stress, inflammation, and telomere attrition. These changes can lead to impaired osteogenic potential and increased adipogenic differentiation. Inflammatory cues disrupt regulatory networks necessary for tissue regeneration. MSCs from older individuals show altered differentiation capabilities, with reduced osteogenic potential and increased adipogenic potential. These changes are linked to systemic inflammation and age-related diseases. MSCs used in regenerative medicine face challenges due to their aging process. Long-term ex-vivo cultivation can lead to senescence, reducing their efficacy. Current methods for MSC expansion and characterization are limited, and there is a need for better understanding of MSC aging to improve clinical applications. Research is ongoing to optimize ex-vivo culture conditions and develop reliable biomarkers for MSC aging. Understanding MSC aging is essential for selecting appropriate donors and ensuring the safety and effectiveness of MSC-based therapies. Further studies are needed to identify specific pathways involved in MSC activation and to develop innovative approaches for clinical translation.