Aging-Related Metaflammation and Mitochondrial Dysfunction in Neurodegenerative Diseases.
Aging-Related Metaflammation and Mitochondrial Dysfunction in Neurodegenerative Diseases.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Incheon, KR · Author affiliation
Department of Biological Sciences and Bioengineering, Inha University, Incheon 22212, Republic of Korea.Location evidence
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Original abstract
Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are increasingly recognized as manifestations of aging-associated systemic dysfunction, rather than isolated brain disorders. Central to this dysfunction is the interplay among metaflammation, mitochondrial breakdown, and chronic neuroinflammation. Metaflammation, driven by peripheral metabolic stress, may prime the brain's immune environment through cytokine signaling and blood-brain barrier compromise. This metabolic-inflammatory crosstalk is thought to impair mitochondrial integrity in neurons and glial cells, promoting oxidative stress and the release of pro-inflammatory mitochondrial components. These mitochondrial signals, in turn, may activate microglial and astrocytic innate immune responses, creating a potentially self-reinforcing cycle of neuroinflammation and energy failure that may contribute to neuronal loss. This review outlines a proposed framework linking metaflammation to neurodegeneration, emphasizing shared mechanisms across AD, PD, and ALS. We further examine preclinical and clinical advances in therapeutic strategies that target this axis including anti-inflammatory agents, caloric restriction, mitophagy enhancers, mitochondrial antioxidants, and senescence-targeted therapies. Together, these interventions reflect a shift from symptom management to systemic metabolic and immune modulation, offering a unified framework for understanding and potentially influencing age-related neurodegeneration.