Metabolic Reprogramming and Redox Adaptation in Age-Associated Inflammation

Chronic inflammation is increasingly understood not as a passive feature of aging, but as an active process rooted in cellular metabolic reprogramming and redox dysregulation. As tissues age, shifts in mitochondrial function, NAD+ metabolism, and ROS signaling converge to sustain a low-grade inflammatory state - widely termed “inflammaging” - that drives immune senescence, tissue dysfunction, and age-associated disease. Dissecting the metabolic and redox mechanisms that initiate and perpetuate this state is one of the central challenges in aging biology.

Conditions characterized by persistent immune activation and external stress offer particularly informative models for studying these mechanisms. For example, in people living with HIV, chronic exposure to residual viral antigens, gut barrier disruption, and viral proteins (such as HIV-1 p17) sustains a pro-inflammatory state that mirrors and accelerates biological aging. Similar accelerated aging dynamics are triggered by other chronic infections, metabolic disorders, and immune-mediated diseases, as well as by environmental factors - including climate change, pollution, and chemical exposures. This suggests shared, targetable redox-metabolic pathways that link environmental stressors, chronic infections, and systemic inflammaging.

This Research Topic brings together mechanistic, translational, and public health research at the intersection of metabolism, redox biology, and age-associated inflammation. We welcome contributions covering, but not limited to:

-Mitochondrial dysfunction, ferroptosis, and ROS/RNS/RSS redox signaling in age-associated inflammatory diseases.
- Organotypic metabolic and immune reprogramming, epigenetics, epitranscriptomics, and post-translational modifications in inflammaging.
- Gut-immune axis disruption as a driver of systemic inflammation and metabolic dysfunction.
- Chronic infection (including HIV, HBV, and other persistent pathogens), immune dysregulation, and accelerated biological aging.
- Climate change, environmental exposures, the exposome, and public health perspectives on accelerated biological aging and inflammaging.
- Multi-omics, single-cell, and systems biology approaches to age-associated inflammation.
- Dietary, pharmacological, lifestyle, or senolytic strategies targeting redox-metabolic pathways in aging.

By integrating expertise across mitochondrial biology, environmental toxicology, and the immunology of aging, this collection aims to map the redox-metabolic landscape of chronic inflammation and identify the intervention points most relevant to healthspan.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Inflammaging, Redox dysregulation, Mitochondrial dysfunction, Metabolic reprogramming, Immune senescence

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.