AUTHOR=Callender Lauren A. , Carroll Elizabeth C. , Garrod-Ketchley Conor , Schroth Johannes , Bystrom Jonas , Berryman Victoria , Pattrick Melanie , Campbell-Richards Desiree , Hood Gillian A. , Hitman Graham A. , Finer Sarah , Henson Sian M. TITLE=Altered Nutrient Uptake Causes Mitochondrial Dysfunction in Senescent CD8+ EMRA T Cells During Type 2 Diabetes JOURNAL=Frontiers in Aging VOLUME=2 YEAR=2021 URL=https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2021.681428 DOI=10.3389/fragi.2021.681428 ISSN=2673-6217 ABSTRACT=

Mitochondrial health and cellular metabolism can heavily influence the onset of senescence in T cells. CD8+ EMRA T cells exhibit mitochondrial dysfunction and alterations to oxidative phosphorylation, however, the metabolic properties of senescent CD8+ T cells from people living with type 2 diabetes (T2D) are not known. We show here that mitochondria from T2D CD8+ T cells had a higher oxidative capacity together with increased levels of mitochondrial reactive oxgen species (mtROS), compared to age-matched control cells. While fatty acid uptake was increased, fatty acid oxidation was impaired in T2D CD8+ EMRA T cells, which also showed an accumulation of lipid droplets and decreased AMPK activity. Increasing glucose and fatty acids in healthy CD8+ T cells resulted in increased p-p53 expression and a fragmented mitochondrial morphology, similar to that observed in T2D CD8+ EMRA T cells. The resulting mitochondrial changes are likely to have a profound effect on T cell function. Consequently, a better understanding of these metabolic abnormalities is crucial as metabolic manipulation of these cells may restore correct T cell function and help reduce the impact of T cell dysfunction in T2D.