PDF(Pubmed)
Abstract：
Sustained exposure to a young systemic environment rejuvenates aged organisms and promotes cellular function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint niche-independent effects of circulating factors on specific cell populations. Here, we describe a method for the encapsulation of human and mouse skeletal muscle progenitors in diffusible polyethersulfone hollow fiber capsules that can be used to profile systemic aging in vivo independent of heterogeneous short-range tissue interactions. We observed that circulating long-range signaling factors in the old systemic environment lead to an activation of Myc and E2F transcription factors, induce senescence, and suppress myogenic differentiation. Importantly, in vitro profiling using young and old serum in 2D culture does not capture all pathways deregulated in encapsulated cells in aged mice. Thus, in vivo transcriptomic profiling using cell encapsulation allows for the characterization of effector pathways of systemic aging with unparalleled accuracy.
摘要：
持续暴露于年轻的系统环境使衰老的生物恢复活力并促进细胞功能。然而,由于组织的内在复杂性,确定循环因子对特定细胞群的生态位无关效应仍然具有挑战性.这里,我们描述了一种将人和小鼠骨骼肌祖细胞封装在可扩散聚醚砜中空纤维胶囊中的方法，该胶囊可用于体内全身性衰老，而与异质的短程组织相互作用无关。我们观察到，在旧的系统环境中循环的长程信号因子导致Myc和E2F转录因子的激活，诱导衰老，并抑制肌源性分化。重要的是,在2D培养中使用年轻和老年血清进行体外分析并不能捕获老年小鼠包封细胞中所有失调的途径。因此，使用细胞封装的体内转录组学分析允许以无与伦比的准确性表征系统性衰老的效应途径。
