STAT3 modulates CD4⁺ T mitochondrial dynamics and function in aging

Area of Science:

• Immunology
• Cellular Aging
• Mitochondrial Biology

Background:

• T cell effector function declines with age.
• Aging is associated with intracellular changes in T cells.
• Mitochondrial dysfunction is implicated in T cell aging.

Purpose of the Study:

• To investigate the role of STAT3 localization in aging T cells.
• To elucidate the impact of mitochondrial STAT3 (mitoSTAT3) on T cell function.
• To explore therapeutic strategies targeting mitoSTAT3.

Main Methods:

• Assessed STAT3 localization in T cells from young and old adults.
• Utilized a mitochondria-targeted STAT3 inhibitor (Mtcur-1).
• Analyzed mitochondrial dynamics, function, and cytokine production.
• Expressed constitutively active STAT3 in T cells from young adults.

Main Results:

• Aging increases STAT3 localization to mitochondria (mitoSTAT3).
• mitoSTAT3 enhances mitochondrial complex II activity, altering dynamics and function.
• Inhibition of mitoSTAT3 with Mtcur-1 reversed age-induced mitochondrial changes and reduced Th17 inflammation.
• Constitutive STAT3 activation in young T cells mimicked aging-related mitochondrial and cytokine profiles.

Conclusions:

• mitoSTAT3 is a key mediator of age-related T cell dysfunction.
• Targeting mitoSTAT3 can restore mitochondrial function and T cell homeostasis.
• This study reveals a novel mechanism linking mitochondrial dynamics, STAT3, and T cell aging.