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Item Type: | Article |
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Title: | In aged primary T cells, mitochondrial stress contributes to telomere attrition measured by a novel imaging flow cytometry assay |
Creators Name: | Sanderson, S.L. and Simon, A.K. |
Abstract: | The decline of the immune system with age known as immune senescence contributes to inefficient pathogen clearance and is a key risk factor for many aged-related diseases. However, reversing or halting immune aging requires more knowledge about the cell biology of senescence in immune cells. Telomere shortening, low autophagy and mitochondrial dysfunction have been shown to underpin cell senescence. While autophagy has been found to control mitochondrial damage, no link has been made to telomere attrition. In contrast, mitochondrial stress can contribute to telomere attrition and vice versa. Whereas this link has been investigated in fibroblasts or cell lines, it is unclear whether this link exists in primary cells such as human lymphocytes and whether autophagy contributes to it. As traditional methods for measuring telomere length are low throughput or unsuitable for the analysis of cell subtypes within a mixed population of primary cells, we have developed a novel sensitive flow-FISH assay using the imaging flow cytometer. Using this assay, we show a correlation between age and increased mitochondrial reactive oxygen species in CD8 T-cell subsets, but not with autophagy. Telomere shortening within the CD8 subset could be prevented in vitro by treatment with a ROS scavenger. Our novel assay is a sensitive assay to measure relative telomere length in primary cells and has revealed ROS as a contributing factor to the decline in telomere length. |
Keywords: | Autophagy, ImageStream, Lymphocytes, Mitochondria, Reactive Oxygen Species, Telomere, T Cells |
Source: | Aging Cell |
ISSN: | 1474-9726 |
Publisher: | Wiley |
Volume: | 16 |
Number: | 6 |
Page Range: | 1234-1243 |
Date: | December 2017 |
Official Publication: | https://doi.org/10.1111/acel.12640 |
PubMed: | View item in PubMed |
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