Neuroinflammaging and Sex-Specific Mechanisms: Biomarker Discovery and Emerging Technological Approaches in Aging Brain Disorders

The progression and advancement of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are significantly influenced by neuroinflammaging, a chronic, low-grade neuroinflammatory state linked to brain aging. This review explores the mechanistic underpinnings of neuroinflammaging, focusing on sex-specific differences in glial cell behavior, cytokine signaling, epigenetic regulation, and blood–brain barrier integrity. Advances in biomarker discovery for early detection and monitoring of aging-related neuroinflammatory processes, highlighting molecules such as interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), chitinase-3-like protein 1 (YKL-40), and neurofilament light, have also been discussed. This review integrates emerging technological and engineering-based strategies from gene editing (clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)) and senolytics to microbiota-based therapeutics, organ-on-chip models, and artificial intelligence-driven predictive tools for intervention and modelling of brain senescence. It also highlights the potential of precision medicine in addressing sex-specific vulnerabilities and designing personalized therapeutic strategies by fusing biological mechanisms with translational technologies. Developing a scalable, system-level therapy that targets neuroinflammaging and promotes healthy brain aging is the goal of this interdisciplinary synthesis.