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

Mohammed Alrouji; Mohammed S. Alshammari; Sharif Alhajlah; Syed Tasqeeruddin; Ghulam Md Ashraf; Khuzin Dinislam; Moyad Shahwan; Anas Shamsi

doi:10.1016/j.eng.2025.12.030

Engineering ›› :202512030 DOI: 10.1016/j.eng.2025.12.030

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

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Abstract

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)-1_b, tumor necrosis factor-_a (TNF-_a), 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.

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Artificial intelligence / Brain aging / CRISPR/Cas9 / Engineering-based interventions / Sex-specific mechanisms

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Mohammed Alrouji, Mohammed S. Alshammari, Sharif Alhajlah, Syed Tasqeeruddin, Ghulam Md Ashraf, Khuzin Dinislam, Moyad Shahwan, Anas Shamsi. Neuroinflammaging and Sex-Specific Mechanisms: Biomarker Discovery and Emerging Technological Approaches in Aging Brain Disorders. Engineering 202512030 DOI:10.1016/j.eng.2025.12.030

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