Serum from Older Adults Increases Apoptosis and Molecular Aging Markers in Human Hippocampal Progenitor Cells.
Serum from Older Adults Increases Apoptosis and Molecular Aging Markers in Human Hippocampal Progenitor Cells.
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DOI：
10.14336/ad.2021.0409
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发表时间：
2021-12
影响因子：
7.4
通讯作者：
Thuret S
中科院分区：
文献类型：
--
作者：
de Lucia C;Murphy T;Maruszak A;Wright P;Powell TR;Hartopp N;de Jong S;O'Sullivan MJ;Breen G;Price J;Lovestone S;Thuret S
与年龄相关的神经干细胞功能改变与神经退行性疾病和认知能力下降有关。在啮齿动物中，这可以通过暴露在年轻的全身环境中而逆转，相反，旧环境可以抑制年轻啮齿动物的干细胞功能。在这项研究中，我们使用成年早期、中年和老年的人血清，研究了人类全身环境对人海马祖细胞(HPC)的体外影响。我们发现，血清处理后的神经母细胞数量预测了更大的齿状回、CA3、CA4和整个海马区的体积，并且来自无症状老年人的同种异体人血清诱导的HPC凋亡细胞死亡是来自年轻人的血清的两倍。一般线性模型显示，增殖和分化标记物的变异性部分归因于抗高血压药物的使用和老年受试者中非常轻微的认知能力下降。最后，使用内表型方法和全基因组表达阵列，我们显示了已建立的和新的衰老分子特征对旧血清的反应上调。来自老年受试者的血清诱导了广泛的细胞和分子表型，可能反映了一生的环境暴露。我们的发现支持系统环境在神经干细胞维持中的作用，并与其他发现一致，强调了神经生物学和时序老化之间的区别。最后，本文所述的血清分析可用于未来的研究，以进一步分析环境暴露的影响以及确定系统环境在健康和疾病中的作用。
Age-related alteration in neural stem cell function is linked to neurodegenerative conditions and cognitive decline. In rodents, this can be reversed by exposure to a young systemic milieu and conversely, the old milieu can inhibit stem cell function in young rodents. In this study, we investigated the in vitro effect of the human systemic milieu on human hippocampal progenitor cells (HPCs) using human serum from early adulthood, mid-life and older age. We showed that neuroblast number following serum treatment is predictive of larger dentate gyrus, CA3, CA4 and whole hippocampus volumes and that allogeneic human serum from asymptomatic older individuals induced a two-fold increase in apoptotic cell death of HPCs compared with serum from young adults. General linear models revealed that variability in markers of proliferation and differentiation was partly attributable to use of antihypertensive medication and very mild cognitive decline among older subjects. Finally, using an endophenotype approach and whole-genome expression arrays, we showed upregulation of established and novel ageing molecular hallmarks in response to old serum. Serum from older subjects induced a wide range of cellular and molecular phenotypes, likely reflecting a lifetime of environmental exposures. Our findings support a role for the systemic enviroment in neural stem cell maintenance and are in line with others highlighting a distinction between neurobiological and chronological ageing. Finally, the herein described serum assay can be used by future studies to further analyse the effect of environmental exposures as well as to determine the role of the systemic environment in health and disease.