Neuroinflammation and cellular senescence in aging: Mechanisms and therapeutic opportunities

Chronological aging is a major risk factor for many neurodegenerative disorders affecting both the brain and the eye, including Alzheimer’s disease, Parkinson’s disease (PD), retinal degeneration, multiple sclerosis , glaucoma, and age-related macular degeneration, and more. Growing evidence suggests that chronic and dysregulated immune activation plays a central role in the development and progression of these diseases. In the aging brain, retinal and optic nerve tissues, sustained activation of innate immune pathways, glial reactivity, complement signaling, and senescence-associated inflammatory responses can disturb tissue homeostasis and contribute to neurodegeneration. Aging-related cellular stressors, such as impaired glucose metabolism, iron accumulation, lipid peroxidation, mitochondrial dysfunction, and defective autophagy, may further intensify inflammatory signaling and immune-mediated tissue damage. In parallel, senescent cells and their secretory phenotype can alter the local immune microenvironment, promoting persistent inflammation and limiting tissue repair. A deeper understanding of how immune, metabolic, and senescence-associated pathways interact in ocular tissues may uncover new biomarkers and therapeutic targets for age-related eye diseases.This Research Topic seeks to advance knowledge of the immune and inflammatory mechanisms that connect aging with retinal and optic nerve degeneration. Particular attention will be given to neuroinflammation, innate and adaptive immune responses, and the contribution of cellular senescence to inflammatory microenvironments in ocular tissues. We welcome studies investigating how metabolic stress, oxidative injury, hypoxia, mitochondrial dysfunction, and impaired lysosomal-autophagic pathways regulate immune activation, glial responses, and inflammatory damage in the aging eye. We are also interested in research exploring how epigenetic and metabolic regulators, including sirtuins and NAD⁺-related pathways, influence immune homeostasis, stress adaptation, and tissue resilience during ocular aging. By integrating molecular immunology, imaging, and translational approaches, this collection aims to identify mechanisms, biomarkers, and therapeutic strategies targeting inflammatory and senescence-associated pathways in age-related ocular disease.This Research Topic welcomes Original Research, Reviews, and Perspectives focused on immune mechanisms and therapeutic strategies in ocular aging and degeneration. Topics of interest include, but are not limited to:• Neuroinflammation and immune cell responses in retinal and optic nerve aging• Innate immune signaling, complement activation, and glial-mediated inflammation in ocular disease• Cellular senescence and the senescence-associated secretory phenotype in the immune microenvironment of ocular tissues• Oxidative stress, hypoxia, and metabolic dysfunction as drivers of inflammatory signaling in the aging eye• Mitochondrial dysfunction, NAD⁺ metabolism, and sirtuin pathways in immunometabolic regulation of retinal health• Lysosomal dysfunction, autophagy, and proteostasis in immune-mediated retinal degeneration• Epigenetic regulation of inflammatory and senescence-associated pathways in ocular aging• Biomarkers and therapeutic targets for immune-driven age-related ocular diseases• Translational and imaging approaches to monitor inflammatory mechanisms and therapeutic responses in retinal disordersSubmissions that link aging and neuron degeneration to well-defined immunological pathways, immune cell functions, or inflammatory mediators are especially encouraged. Topic editors: Wensi Tao, Nai-Kei Wong, Hong Yu Source: https://www.frontiersin.org/research-topics/79980/neuroinflammation-and-cellular-senescence-in-aging-mechanisms-and-therapeutic-opportunities