Abstract

Aging promotes numerous intracellular changes in T cells that impact their effector function. Our data show that aging promotes an increase in the localization of STAT3 to the mitochondria (mitoSTAT3), which promotes changes in mitochondrial dynamics and function and T-cell cytokine production. Mechanistically, mitoSTAT3 increased the activity of aging T-cell mitochondria by increasing complex II. Limiting mitoSTAT3 using a mitochondria-targeted STAT3 inhibitor, Mtcur-1 lowered complex II activity, prevented age-induced changes in mitochondrial dynamics and function, and reduced Th17 inflammation. Exogenous expression of a constitutively phosphorylated form of STAT3 in T cells from young adults mimicked changes in mitochondrial dynamics and function in T cells from older adults and partially recapitulated aging-related cytokine profiles. Our data show the mechanistic link among mitoSTAT3, mitochondrial dynamics, function, and T-cell cytokine production.

Document Type

Article

Publication Date

10-2023

Notes/Citation Information

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

Digital Object Identifier (DOI)

https://doi.org/10.1111/acel.13996

Funding Information

This work was supported by R15AG068957 (LPB), pilot award from the San Diego Nathan Shock Center of Excellence in the Basic Biology of Aging NIH P30AG068635 (LPB) and R56AG06985 (BSN), T32NS115667 (MKK). R01AG076075 (MJD) and supported by the Pasini Fellowship (LPB), College of Health Sciences Faculty Development grant (FDG) (LPB), and Sakowich Center for Undergraduate Research and Creative Activities grant (SCURCA), Merrimack College (LPB), College of Health Sciences, Merrimack College and Barnstable Brown Diabetes Center, University of Kentucky (BSN).

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