Sanford-Burnham-Prebys Medical Discovery Institute at Lake Nona, Orlando, Florida.
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Aging Cell. 2018 Oct;17(5):e12815. doi: 10.1111/acel.12815. Epub 2018 Jul 12.
Tissue regeneration is a highly coordinated process with sequential events including immune cell infiltration, clearance of damaged tissues, and immune-supported regrowth of the tissue. Aging has a well-documented negative impact on this process globally; however, whether changes in immune cells per se are contributing to the decline in the body's ability to regenerate tissues with aging is not clearly understood. Here, we set out to characterize the dynamics of macrophage infiltration and their functional contribution to muscle regeneration by comparing young and aged animals upon acute sterile injury. Injured muscle of old mice showed markedly elevated number of macrophages, with a predominance for Ly6C pro-inflammatory macrophages and a lower ratio of the Ly6C repair macrophages. Of interest, a recently identified repair macrophage-derived cytokine, growth differentiation factor 3 (GDF3), was markedly downregulated in injured muscle of old relative to young mice. Supplementation of recombinant GDF3 in aged mice ameliorated the inefficient regenerative response. Together, these results uncover a deficiency in the quantity and quality of infiltrating macrophages during aging and suggest that in vivo administration of GDF3 could be an effective therapeutic approach.
组织再生是一个高度协调的过程，包括一系列事件，包括免疫细胞浸润、损伤组织的清除以及免疫支持组织的再生。衰老对这一过程有明确的负面影响；然而，免疫细胞的变化本身是否导致机体随着年龄的增长而丧失组织再生能力尚不清楚。在这里，我们通过比较急性无菌损伤时的年轻和老年动物，旨在描述巨噬细胞浸润的动态及其对肌肉再生的功能贡献。老年小鼠受伤肌肉中的巨噬细胞数量明显增加，以 Ly6C 促炎巨噬细胞为主，Ly6C 修复型巨噬细胞的比例较低。有趣的是，一种最近发现的修复型巨噬细胞衍生细胞因子，生长分化因子 3（GDF3），在老年小鼠受伤肌肉中的表达明显低于年轻小鼠。在老年小鼠中补充重组 GDF3 可改善低效的再生反应。总之，这些结果揭示了衰老过程中浸润巨噬细胞数量和质量的不足，并表明体内给予 GDF3 可能是一种有效的治疗方法。
