UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Mitochondrial mass governs the extent of human T cell senescence

Callender, LA; Carroll, EC; Bober, EA; Akbar, AN; Solito, E; Henson, SM; (2019) Mitochondrial mass governs the extent of human T cell senescence. Aging Cell , Article e13067. 10.1111/acel.13067. (In press). Green open access

[thumbnail of Callender_et_al-2019-Aging_Cell.pdf]
Preview
Text
Callender_et_al-2019-Aging_Cell.pdf - Published Version

Download (1MB) | Preview

Abstract

The susceptibility of human CD4+ and CD8+ T cells to senesce differs, with CD8+ T cells acquiring an immunosenescent phenotype faster than the CD4+ T cell compartment. We show here that it is the inherent difference in mitochondrial content that drives this phenotype, with senescent human CD4+ T cells displaying a higher mitochondrial mass. The loss of mitochondria in the senescent human CD8+ T cells has knock‐on consequences for nutrient usage, metabolism and function. Senescent CD4+ T cells uptake more lipid and glucose than their CD8+ counterparts, leading to a greater metabolic versatility engaging either an oxidative or a glycolytic metabolism. The enhanced metabolic advantage of senescent CD4+ T cells allows for more proliferation and migration than observed in the senescent CD8+ subset. Mitochondrial dysfunction has been linked to both cellular senescence and aging; however, it is still unclear whether mitochondria play a causal role in senescence. Our data show that reducing mitochondrial function in human CD4+ T cells, through the addition of low‐dose rotenone, causes the generation of a CD4+ T cell with a CD8+‐like phenotype. Therefore, we wish to propose that it is the inherent metabolic stability that governs the susceptibility to an immunosenescent phenotype.

Type: Article
Title: Mitochondrial mass governs the extent of human T cell senescence
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/acel.13067
Publisher version: https://doi.org/10.1111/acel.13067
Language: English
Additional information: Copyright © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: T cell, aging, metabolism, mitochondria, senescence
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10088632
Downloads since deposit
47Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item