Gopinath Suchitra D, Rando Thomas A
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305-5235, USA.
Aging Cell. 2008 Aug;7(4):590-8. doi: 10.1111/j.1474-9726.2008.00399.x. Epub 2008 Jun 28.
Declining stem cell function during aging contributes to impaired tissue function. Muscle-specific stem cells ('satellite cells') are responsible for generating new muscle in response to injury in the adult. However, aged muscle displays a significant reduction in regenerative abilities and an increased susceptibility to age-related pathologies. This review describes components of the satellite cell niche and addresses how age-related changes in these components impinge on satellite cell function. In particular, we review changes in the key niche elements, the myofiber and the basal lamina that are in intimate contact with satellite cells. We address how these elements are influenced by factors secreted by interstitial cells, cells of the immune system, and cells associated with the vasculature, all of which change with age. In addition, we consider more distant sources of influence on the satellite cell niche that change with age, such as neural-mediated trophic factors and electrical activity and systemic factors present in the circulation. A better understanding of the niche elements and their influence on the satellite cell will facilitate the development of therapeutic interventions aimed at improving satellite cell activity and ultimately tissue response to injury in aged individuals.
衰老过程中干细胞功能的衰退会导致组织功能受损。肌肉特异性干细胞(“卫星细胞”)负责在成年个体受伤时生成新的肌肉。然而,老年肌肉的再生能力显著下降,且对与年龄相关的病理变化的易感性增加。本综述描述了卫星细胞微环境的组成部分,并探讨了这些组成部分中与年龄相关的变化如何影响卫星细胞功能。特别是,我们回顾了与卫星细胞紧密接触的关键微环境要素——肌纤维和基膜的变化。我们探讨了这些要素如何受到间质细胞、免疫系统细胞以及与脉管系统相关细胞分泌的因子的影响,所有这些因子都会随着年龄的增长而发生变化。此外,我们还考虑了随着年龄增长而对卫星细胞微环境产生影响的更远距离的因素,如神经介导的营养因子、电活动以及循环中存在的全身因素。更好地理解微环境要素及其对卫星细胞的影响,将有助于开发旨在改善卫星细胞活性并最终改善老年个体组织对损伤反应的治疗干预措施。