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Instructor/Advisor

Dr. Leena Bharath

Keywords

aging, T-cells, mitochondria

Abstract

Aging promotes numerous intracellular changes in CD4 + T cells that impact their effector function. Our prior work showed that T cells from older(O) adults had higher expression and activity of mitochondrial complex II (Succinate dehydrogenase (SDH)). T cells from O adults also had altered mitochondrial dynamics with increased mitochondrial content, branching, and fission, reduced fusion, and dysregulation in TCA cycle metabolites compared to T cells from young(Y) adults. Aim: The objective of our study is to evaluate if pharmacological and genetic modulation of SDH would restore a “young” mitochondrial phenotype in T cells from O adults. Methods: CD4 + T cells were isolated from lean normoglycemic young (Y; avg: 31.81 yrs; BMI 22.20 kg/m 2 ) and older (O; avg: 68.11 yrs; BMI 23.46 kg/m 2 ) adults. Mitochondrial structure, dynamics, function, and TCA cycle metabolites were assessed after pharmacological activation (Diethyl Succinate) and inhibition (3-nitro propionic acid) and genetic inhibition (siRNA) of SDH in T cells from Y and O adults. Results: Our data shows that SDH activation is critical for the induction of age-related mitochondrial changes. Preventing hyper-activation of SDH restores cellular levels of TCA cycle metabolites and rejuvenates mitochondrial structure, function, and dynamics, thus recapitulating a young mitochondrial phenotype.

Succinate Dehydrogenase Impacts T Cell Inflammation by Regulating Mitochondrial Structure and Function

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