Early-Life Red Light Exposure Extends Lifespan in C. elegans through ROS-AMPK-Driven Mitochondrial Reprogramming.

Specific wavelengths and intensities of light offer potential for modulating mitochondrial function to influence aging which is important for the development of non-invasive and modifiable exogenous anti-aging tools. However, the effects of exposure to different wavelengths of light during the early stages of life on health in adulthood, and the underlying mechanisms, remain poorly understood. In this study, we utilized Caenorhabditis elegans to investigate the effects of early-life (L1 to young adult stage) exposure to different light wavelengths (white, red, blue, green) on healthspan(definition). We found that red light exposure (630 nm, 200 lx) during early life extended lifespan by 10.34% without affecting growth, movement, or reproduction, and improved late-life health indicators. Importantly, it significantly enhanced healthspan in later life, suggesting its potential as a non-invasive anti-aging strategy. Mechanistically, red light transiently suppressed mitochondrial bioenergetic activity, biogenesis, and membrane potential, and altered mitochondrial dynamics. Upon light withdrawal, mitochondrial function progressively recovered, demonstrating enhanced structure and function by day 6. Furthermore, red light stimulated ROS production, activated AMPKα phosphorylation, and triggered downstream mitochondrial quality control (MQC) programs, including the unfolded protein response (UPR^MT) and mitophagy. Notably, these protective effects were conserved in human dermal fibroblasts, suggesting the translational applicability of this pathway. Collectively, our study identifies a specific "photophysiological window" during early life through which red light promotes longevity via ROS-mediated activation of AMPK and enhancement of MQC, proposing a non-invasive, safe, evolutionarily conserved, and drug-free strategy to mitigate age-related mitochondrial decline. Therefore, red light can serve as a non-invasive anti-aging strategy to enhance healthspan and potentially alleviate age-related mitochondrial dysfunction(definition).