Chemokines and redox homeostasis in aging: A dynamic relationship.

Abstract

Chemokines are small cytokines that are essential for recruiting immune cells and modulating inflammatory responses. Their expression and activity are tightly regulated by redox homeostasis, which influences cellular signaling and immune function through dynamic interactions with reactive oxygen and nitrogen species (ROS and RNS). Redox-sensitive transcription factors, such as NF-κB, and post-translational modifications, including glutathionylation, help fine-tune chemokine expression and receptor activity. Conversely, chemokines and their receptors also affect cellular oxidative states, notably by modulating ROS production via NADPH oxidase activation. This review explores the bidirectional interplay between chemokine signaling and redox homeostasis, particularly focusing on how this relationship shapes the progression of aging and age-related diseases. By synthesizing findings from clinical studies, preclinical models, and mechanistic investigations published in the last five years, we highlight the relevance of chemokine-redox interactions in conditions such as Alzheimer's disease and atherosclerosis. Finally, we discuss emerging therapeutic approaches that modulate both chemokine signaling and oxidative stress to restore immune balance and mitigate age-associated tissue damage.