小柯机器人

近日，美国杰克逊实验室Jennifer J. Trowbridge及其研究团队发现，骨髓微环境中IGF1的下降引发造血干细胞的衰老。该项研究成果于2021年4月12日在线发表在《细胞—干细胞》杂志上。

通过在小鼠中进行横断面研究，研究人员发现，造血干细胞（HSC）和造血功能的衰老标志在中年以前就开始积累，并且中年的骨髓（BM）微环境可诱导造血衰老，这是必不可少的。使用无偏方法，研究人员发现在局部中年BM微环境中，长寿相关分子IGF1的水平降低是导致HSC衰老的一个因素。

用IGF1直接刺激中年HSC可以挽救衰老的分子和功能特征，包括恢复线粒体活性。因此，尽管IGF1的下降可延长寿命，但这个工作表明这也损害了HSC的功能并限制了造血健康的寿命。

据了解，随着年龄的增长，HSC功能下降是人类血液和免疫系统健康状况有限的原因。为了使健康保持到老年，有必要了解引发HSC衰老事件的性质和时机。 

附：英文原文

Title: Decline in IGF1 in the bone marrow microenvironment initiates hematopoietic stem cell aging

Author: Kira Young, Elizabeth Eudy, Rebecca Bell, Matthew A. Loberg, Tim Stearns, Devyani Sharma, Lars Velten, Simon Haas, Marie-Dominique Filippi, Jennifer J. Trowbridge

Issue&Volume: 2021-04-12

Abstract: Decline in hematopoietic stem cell (HSC) function with age underlies limited healthspan of our blood and immune systems. In order to preserve health into older age,it is necessary to understand the nature and timing of initiating events that causeHSC aging. By performing a cross-sectional study in mice, we discover that hallmarksof aging in HSCs and hematopoiesis begin to accumulate by middle age and that thebone marrow (BM) microenvironment at middle age induces and is indispensable for hematopoieticaging. Using unbiased approaches, we find that decreased levels of the longevity-associatedmolecule IGF1 in the local middle-aged BM microenvironment are a factor causing HSCaging. Direct stimulation of middle-aged HSCs with IGF1 rescues molecular and functionalhallmarks of aging, including restored mitochondrial activity. Thus, although declinein IGF1 supports longevity, our work indicates that this also compromises HSC functionand limits hematopoietic health span.

DOI: 10.1016/j.stem.2021.03.017

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00123-5

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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