Skeletal muscle regeneration that follows acute injury is strongly influenced by interactions with immune cells that invade and proliferate in the damaged tissue. Discoveries over the past 20 years have identified many of the key mechanisms through which myeloid cells, especially macrophages, regulate muscle regeneration. In addition, lymphoid cells that include CD8+ T-cells and regulatory T-cells also significantly affect the course of muscle regeneration. During aging, the regenerative capacity of skeletal muscle declines, which can contribute to progressive loss of muscle mass and function. Those age-related reductions in muscle regeneration are accompanied by systemic, age-related changes in the immune system, that affect many of the myeloid and lymphoid cell populations that can influence muscle regeneration. In this review, we present recent discoveries that indicate that aging of the immune system contributes to the diminished regenerative capacity of aging muscle. Intrinsic, age-related changes in immune cells modify their expression of factors that affect the function of a population of muscle stem cells, called satellite cells, that are necessary for normal muscle regeneration. For example, age-related reductions in the expression of growth differentiation factor-3 (GDF3) or CXCL10 by macrophages negatively affect adult myogenesis, by disrupting regulatory interactions between macrophages and satellite cells. Those changes contribute to a reduction in the numbers and myogenic capacity of satellite cells in old muscle, which reduces their ability to restore damaged muscle. In addition, aging produces changes in the expression of molecules that regulate the inflammatory response to injured muscle, which also contributes to age-related defects in muscle regeneration. For example, age-related increases in the production of osteopontin by macrophages disrupts the normal inflammatory response to muscle injury, resulting in regenerative defects. These nascent findings represent the beginning of a newly-developing field of investigation into mechanisms through which aging of the immune system affects muscle regeneration.

急性损伤后的骨骼肌再生受到与在受损组织中侵入和增殖的免疫细胞相互作用的强烈影响。过去 20 年的发现已经确定了骨髓细胞（尤其是巨噬细胞）调节肌肉再生的许多关键机制。此外，包括 CD8+ T 细胞和调节性 T 细胞的淋巴样细胞也显着影响肌肉再生过程。在衰老过程中，骨骼肌的再生能力下降，这可能导致肌肉质量和功能的逐渐丧失。这些与年龄相关的肌肉再生减少伴随着免疫系统中与年龄相关的全身性变化，这些变化会影响许多可影响肌肉再生的骨髓和淋巴样细胞群。在本次审查中，我们最近的发现表明，免疫系统的老化会导致老化肌肉的再生能力下降。免疫细胞内在的、与年龄相关的变化会改变其影响肌肉干细胞群（称为卫星细胞）功能的因子表达，这些是正常肌肉再生所必需的。例如，与年龄相关的巨噬细胞生长分化因子 3 (GDF3) 或 CXCL10 表达的减少会破坏巨噬细胞和卫星细胞之间的调节相互作用，从而对成人肌生成产生负面影响。这些变化有助于减少旧肌肉中卫星细胞的数量和生肌能力，从而降低它们恢复受损肌肉的能力。此外，衰老会导致调节受损肌肉炎症反应的分子表达发生变化，这也导致与年龄相关的肌肉再生缺陷。例如，与年龄相关的巨噬细胞产生的骨桥蛋白会破坏对肌肉损伤的正常炎症反应，从而导致再生缺陷。这些新发现代表了一个新的研究领域的开始，即研究免疫系统老化影响肌肉再生的机制。