Network Destabilization in Aging: Mitochondrial Dysfunction, Nutrient Sensing, and Chronic Inflammation as...

Area of Science:

• Gerontology and Systems Biology
• Mitochondrial Biology
• Inflammology

Background:

• Aging is the primary risk factor for numerous chronic diseases, but the underlying mechanisms linking them are not fully understood.
• Current aging frameworks identify key hallmarks but don't fully explain organism-level decline and multimorbidity.
• A systems-level perspective is needed to integrate aging processes across biological scales.

Purpose of the Study:

• To introduce a systems-level framework conceptualizing aging as progressive destabilization of interacting regulatory networks.
• To propose a high-centrality network core involving mitochondrial quality control, nutrient-sensing, and inflammatory signaling.
• To provide a mechanistic basis for the convergence of various age-related diseases.

Main Methods:

• This is a narrative and conceptual review integrating evidence from mitochondrial biology, metabolic signaling, and inflammatory pathways.
• The study proposes a hypothesis-generating framework, not a formally validated model.
• Evidence is synthesized to support the concept of aging as network destabilization.

Main Results:

• Aging is framed as the progressive destabilization of interacting regulatory networks, with a core network involving mitochondria, nutrient sensing, and inflammation.
• Network instability explains the convergence of diverse age-related diseases (neurodegenerative, cardiovascular, metabolic, oncological).
• Reframing aging hallmarks as network nodes emphasizes system-level resilience and non-linear dynamics.

Conclusions:

• Targeting high-centrality network nodes (e.g., mTOR, NAD+, mitophagy, inflammation) may yield system-wide benefits for aging and disease.
• Interventions may reconfigure network dynamics for broader effects than single-pathway corrections.
• Biomarker-stratified, network-calibrated interventions could provide a more comprehensive therapeutic strategy for aging-related conditions.