Network Physiology of Aging: Neuroplasticity, Connectivity Dynamics, and Interventions in Resting-State Brain Networks

Aging represents a profound physiological process that manifests across multiple levels of biological organization, fundamentally altering the dynamic interactions among bodily systems—including the brain’s large-scale resting-state networks (RSNs). The default mode network (DMN), along with executive control and salience networks, plays a pivotal role in integrating sensory, cognitive, and internal states, underpinning both healthy and pathological brain aging.

Recent advances in neuroimaging modalities—such as functional MRI (fMRI), diffusion tensor imaging (DTI), and electroencephalography (EEG)—combined with network neuroscience and physiological modeling have revealed that aging is associated with complex reconfigurations in network dynamics, connectivity, and cross-talk between neural systems. Notably, structural changes (e.g., cortical thinning, loss of white matter integrity) are paralleled by dynamic shifts in network efficiency, integration, information flow, and compensatory recruitment of alternative neural pathways. These processes are not isolated to the brain but may reflect broader physiological adaptation in response to aging, with implications for cognition, homeostasis, and systemic health.

In pathological aging and neurodegenerative diseases, such as Alzheimer’s disease, disruptions in brain network modularity, loss of hub integrity, and breakdown in long-range connectivity have been linked to system-wide dysregulation, cognitive impairment, and altered physiological states. Characterizing these changes from a network physiology perspective—across time, spatial scales, and in relation to other organ systems—offers vital insights into both the mechanisms of resilience and the early markers of dysfunction.

Despite significant progress, key questions remain unresolved, including the temporal trajectory of network alterations, their potential reversibility, interactions with cardiovascular or metabolic systems, and modulation through behavioral, cognitive, or physiological interventions.

Frontiers in Network Physiology invites original research, systematic reviews, and methodological contributions that advance our understanding of how RSNs evolve during healthy and pathological aging, particularly by situating brain network changes within the broader context of physiological network dynamics. We encourage submissions that utilize multimodal imaging, longitudinal or cross-scale datasets, and advanced network analytic techniques to address the following (but not limited to) topics:

1. Trajectories of Change: Do alterations in brain network efficiency, integration, and modularity follow linear, nonlinear, or critical transition patterns with aging?

2. Network-Physiology Interactions: How do age-related changes in core brain networks (DMN, frontoparietal, salience) interface with other body systems (e.g., autonomic, cardiovascular) at rest and during challenges?

3. Mechanisms of Compensation: How can compensatory or maladaptive neuroplastic changes in network dynamics be quantified using physiologically inspired metrics?

4. Effects of Interventions: Can cognitive, physical, or lifestyle interventions induce measurable reconfiguration of RSN and systemic physiological networks? What are the optimal analytic frameworks for detecting such effects?

5. Biomarkers & Early Detection: What quantitative markers of network physiology best predict cognitive decline or neurodegenerative risk, and how robust are these markers across methods and populations?

6. Methods & Models: What novel analytical models (e.g., cross-modal data fusion, temporal network modeling, machine learning) enhance our ability to probe dynamic physiological states and network-level biomarkers?

We particularly welcome interdisciplinary studies that integrate structural, functional, and behavioral data to elucidate how brain networks interact with broader physiological systems during aging, or that propose and validate biomarkers with translational potential for early intervention. Theoretical and computational innovations that refine our understanding of network regulation, resilience, or tipping points in physiology are also of high interest.

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• Case Report
• Classification
• Clinical Trial
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• Editorial
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Article types

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

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

Keywords: Network Physiology, Brain Aging, Cognitive Decline, Default Mode Network, Functional Connectivity, Multimodal Neuroimaging, Network Neuroscience, Systems Biology, Resting-State Networks

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.