Aging Delays Epimorphic Regeneration in Mice
Aging Delays Epimorphic Regeneration in Mice
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DOI：
10.1093/gerona/glab131
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发表时间：
2021-05-10
影响因子：
5.1
通讯作者：
Muneoka, Ken
中科院分区：
文献类型：
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作者：
Brunauer, Regina;Xia, Ian G.;Muneoka, Ken
表型再生是一种多组织再生过程，截肢不会导致瘢痕形成，而是胚泡的形成和图案化的形态发生，其中细胞可塑性和协调的细胞-细胞相互作用是关键。组织再生随着年龄的增长而下降，但衰老是否以及如何损害表型再生尚不清楚。在这里，我们首次表明，衰老破坏了哺乳动物表型再生的时空调节，第一，通过加剧组织溶解和推迟伤口闭合，第二，通过损害胚芽分化和骨骼再生。令人惊讶的是，衰老并没有限制胚泡中干细胞的可获得性，而是减少了成骨细胞依赖的骨形成。我们的数据表明，衰老延迟再生不是由于干细胞耗尽，而是分化细胞的功能缺陷，这可能是由老化的创伤环境和再生事件时空调节的变化所驱动的。我们的发现强调了再生信号事件的准确时机的重要性，并强调了再生医学中谨慎时机干预的必要性。
Epimorphic regeneration is a multitissue regeneration process where amputation does not lead to scarring, but blastema formation and patterned morphogenesis for which cell plasticity and concerted cell-cell interactions are pivotal. Tissue regeneration declines with aging, yet if and how aging impairs epimorphic regeneration is unknown. Here, we show for the first time that aging derails the spatiotemporal regulation of epimorphic regeneration in mammals, first, by exacerbating tissue histolysis and delaying wound closure, and second, by impairing blastema differentiation and skeletal regrowth. Surprisingly, aging did not limit stem cell availability in the blastema but reduced osteoblast-dependent bone formation. Our data suggest that aging delays regeneration not by stem cell exhaustion, but functional defects of differentiated cells that may be driven by an aged wound environment and alterations in the spatiotemporal regulation of regeneration events. Our findings emphasize the importance of accurate timing of signaling events for regeneration and highlight the need for carefully timed interventions in regenerative medicine.