Senescence of skeletal stem cells and their contribution to age-related bone loss

• Published in: Mechanisms of ageing and development 2024-10, Vol.221, p.111976, Article 111976
• Main Authors: Wölfel, Eva M., Fernandez-Guerra, Paula, Nørgård, Mikkel Ørnfeldt, Jeromdesella, Shakespeare, Kjær, Pernille Kirkegaard, Elkjær, Anna Sofie, Kassem, Moustapha, Figeac, Florence
• Format: Article
• Language: English
• Subjects: Age-related bone disease; Cellular senescence; Marrow stromal stem cells; Skeletal stem cells
• ISSN: 0047-6374; 1872-6216; 1872-6216
• DOI: 10.1016/j.mad.2024.111976

Human aging is linked to bone loss, resulting in bone fragility and an increased risk of fractures. This is primarily due to an age-related decline in the function of bone-forming osteoblastic cells and accelerated cellular senescence within the bone microenvironment. Here, we provide a detailed discussion of the hypothesis that age-related defective bone formation is caused by senescence of skeletal stem cells, as they are the main source of bone forming osteoblastic cells and influence the composition of bone microenvironment. Furthermore, this review discusses potential strategies to target cellular senescence as an emerging approach to treat age-related bone loss. •Age-related impaired bone formation is caused by accelerated senescence of skeletal stem cells (marrow stromal stem cells).•Skeletal stem cell function and metabolism is impaired by cellular and molecular mechanisms that drive cellular senescence.•Therapeutic intervention reduces bone loss and maintains age-related skeletal health by descreasing cellular senescence.