Aging Suppresses Skin-Derived Circulating SDF1 to Promote Full-Thickness Tissue Regeneration.
Aging Suppresses Skin-Derived Circulating SDF1 to Promote Full-Thickness Tissue Regeneration.
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DOI：
10.1016/j.celrep.2018.08.054
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发表时间：
2018-09-25
期刊：
影响因子：
8.8
通讯作者：
Leung TH
中科院分区：
文献类型：
--
作者：
Nishiguchi MA;Spencer CA;Leung DH;Leung TH
医生们观察到，老年人的手术伤口愈合时留下的疤痕比年轻患者的伤口要薄。了解这种现象可能会揭示促进无瘢痕伤口修复的策略。我们发现，老年小鼠的全层皮肤伤口可以完全再生，但年轻小鼠不能。老年动物通过共生接触年轻小鼠的血液会抵消这种再生能力。分泌的因子，基质衍生因子1（SDF 1），在年轻小鼠受伤的皮肤中以较高的水平表达。年轻皮肤中SDF 1基因缺失增强组织再生。在老年小鼠中，zeste同源物2（EZH2）和组蛋白H3赖氨酸27三甲基化的增强子以更高水平被募集到SDF 1启动子，并且EZH2的药理学抑制恢复SDF 1诱导并防止组织再生。类似的年龄依赖性EZH2介导的SDF 1抑制发生在人类皮肤中。我们的研究结果反驳了目前的教条，即组织功能总是随着年龄的增长而下降，并提出了再生医学的新治疗策略。Nishiguchi等人表明，衰老促进小鼠皮肤的全层组织再生。衰老调节SDF 1基因的染色质可及性，年轻皮肤中SDF 1的基因缺失增强了组织再生。人类皮肤也表现出年龄依赖性的SDF 1抑制。他们发现了一个罕见的例子，即衰老改善了组织功能。
Physicians have observed that surgical wounds in the elderly heal with thinner scars than wounds in young patients. Understanding this phenomenon may reveal strategies for promoting scarless wound repair. We show that full-thickness skin wounds in aged but not young mice fully regenerate. Exposure of aged animals to blood from young mice by parabiosis counteracts this regenerative capacity. The secreted factor, stromal-derived factor 1 (SDF1), is expressed at higher levels in wounded skin of young mice. Genetic deletion of SDF1 in young skin enhanced tissue regeneration. In aged mice, enhancer of zeste homolog 2 (EZH2) and histone H3 lysine 27 trimethylation are recruited to the SDF1 promoter at higher levels, and pharmacologic inhibition of EZH2 restores SDF1 induction and prevents tissue regeneration. Similar age-dependent EZH2-mediated SDF1 suppression occurs in human skin. Our findings counter the current dogma that tissue function invariably declines with age and suggest new therapeutic strategies in regenerative medicine. Nishiguchi et al. show that aging promotes full-thickness tissue regeneration in mouse skin. Aging modulates chromatin accessibility at the SDF1 gene, and genetic deletion of SDF1 in young skin enhances tissue regeneration. Human skin also exhibits age-dependent SDF1 suppression. They identify a rare example where aging improves tissue function.
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