Rejuvenation of aged progenitor cells by exposure to a young systemic environment
Rejuvenation of aged progenitor cells by exposure to a young systemic environment
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DOI：
10.1038/nature03260
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发表时间：
2005-02-17
期刊：
影响因子：
64.8
通讯作者：
Rando, TA
中科院分区：
文献类型：
--
作者：
Conboy, IM;Conboy, MJ;Rando, TA
组织再生潜力的下降是衰老的标志，可能是由于组织特异性干细胞中与年龄相关的变化（1-5）。由于Notch信号传导的丧失导致骨骼肌干细胞（卫星细胞）活性下降，导致老化肌肉的再生受损（1，6）。由于涉及cEBP-α和染色质重塑因子brahma（Brm）的复合物的形成，肝祖细胞增殖的下降抑制了老化肝脏的再生能力（7）。为了研究全身因素对来自这些组织的老年祖细胞的影响，我们在年轻和老年小鼠（异时性parabioses）之间建立了联体配对（即共享的循环系统），将老年小鼠暴露于年轻血清中存在的因素。值得注意的是，异时共生恢复了Notch信号的激活以及老化卫星细胞的增殖和再生能力。将来自老年小鼠的卫星细胞暴露于年轻血清增强了Notch配体（Delta）的表达，增加了Notch活化，并增强了体外增殖。此外，异时共生增加了老年肝细胞增殖，并将cEBP-α复合物恢复到年轻动物中观察到的水平。这些结果表明，与年龄相关的祖细胞活性下降可以通过随年龄变化的全身因素进行调节。
The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in tissue-specific stem cells(1-5). A decline in skeletal muscle stem cell ( satellite cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle(1,6). The decline in hepatic progenitor cell proliferation owing to the formation of a complex involving cEBP-alpha and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver(7). To examine the influence of systemic factors on aged progenitor cells from these tissues, we established parabiotic pairings ( that is, a shared circulatory system) between young and old mice (heterochronic parabioses), exposing old mice to factors present in young serum. Notably, heterochronic parabiosis restored the activation of Notch signalling as well as the proliferation and regenerative capacity of aged satellite cells. The exposure of satellite cells from old mice to young serum enhanced the expression of the Notch ligand ( Delta), increased Notch activation, and enhanced proliferation in vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte proliferation and restored the cEBP-alpha complex to levels seen in young animals. These results suggest that the age-related decline of progenitor cell activity can be modulated by systemic factors that change with age.