Inflammaging Module

Module inflammaging 1 disorder Pathograph 4

A conserved mechanism module for the intertwined hallmarks of aging (Lopez-Otin et al.) termed altered intercellular communication and chronic inflammation - together the phenomenon of "inflammaging": the chronic, low-grade, sterile systemic inflammation that develops with age in the absence of overt infection. Multiple age-associated stimuli converge to sustain it - the senescence-associated secretory phenotype (SASP), damage-associated molecular patterns from dysfunctional mitochondria, NLRP3 inflammasome activation, increased gut permeability and microbiota shifts, central obesity, immune dysregulation, and chronic infections. The resulting persistent cytokine milieu, propagated systemically through altered intercellular communication, is a highly significant risk factor for morbidity and mortality because most age-related diseases share an inflammatory pathogenesis. Individual disorder entries declare conformance via conforms_to on their pathophysiology nodes, substituting the disease-specific inflammatory driver and target tissue while preserving the conserved stimulus -> chronic-sterile-inflammation -> systemic-propagation -> age-related-morbidity chain.

⚙

Pathophysiology Nodes

4 shared nodes are defined in this module.

◉

Cell Types

No cell types are annotated for this module.

⇄

Biological Processes

Notes

This is a mechanism module, not a specific disease. Disorder entries reference individual nodes via conforms_to (e.g., "inflammaging#Chronic Low-Grade Sterile Inflammation"). Conforming nodes in disorder files should include the corresponding biological processes and causal edges, specialized to their disease context. The module captures the conserved inflammaging chain and its role as a shared risk substrate for age-related disease; it deliberately does NOT re-derive the SASP (see cellular_senescence) or adjudicate which upstream source dominates in a given disease. It is the systemic-inflammation convergence point downstream of cellular_senescence and mitochondrial_dysfunction. Key conformance target: "inflammaging#Chronic Low-Grade Sterile Inflammation".

↗

Used By Disorder Entries

Hutchinson-Gilford Progeria Syndrome via ATM-NF-kB systemic inflammation → Chronic Low-Grade Sterile Inflammation

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence-backed metadata.

⚙

Pathophysiology

Age-Associated Inflammatory Stimuli

trigger

A diverse set of age-accumulating stimuli feed sterile inflammation: senescent-cell SASP, damage-associated molecular patterns from dysfunctional mitochondria, NLRP3 inflammasome activation, increased gut permeability and microbiota changes, central obesity, immune-cell dysregulation, and chronic infections. Regardless of the dominant source, these converge to drive a persistent inflammatory response.

Inflammatory Response GO:0006954 INCREASED

Downstream

Chronic Low-Grade Sterile Inflammation

Chronic Low-Grade Sterile Inflammation

central effector

The persistent stimuli establish a chronic, low-grade, sterile inflammatory state - elevated circulating inflammatory mediators without overt infection. This is the defining central effector of inflammaging and the conserved node that disease-specific inflammatory drivers converge upon.

Inflammatory Response GO:0006954 INCREASED Cytokine Production GO:0001816 INCREASED

Used by disorders

Hutchinson-Gilford Progeria Syndrome as ATM-NF-kB systemic inflammation

Downstream

Systemic Propagation via Altered Intercellular Communication

Systemic Propagation via Altered Intercellular Communication

amplifier

The inflammatory state is propagated beyond its cells of origin through altered intercellular communication - circulating cytokines, chemokines, and other mediators acting at a distance. This systemic cytokine signaling is the amplifying step that converts local inflammatory sources into a body-wide aging phenotype, and is itself one of the enumerated hallmarks of aging.

Cytokine-Mediated Signaling GO:0019221 INCREASED

Downstream

Age-Related Morbidity and Mortality