Chronic Inflammation and Inflammaging

Key Takeaways

Inflammaging describes persistent, generally low-grade inflammatory activity associated with ageing; it is not simply an acute immune response lasting longer. [1] [2]
Potential contributors include senescent cells, tissue damage, mitochondrial stress, immune dysregulation, altered barriers, infections, adipose tissue, and microbiome-related signals. [1] [3]
Inflammation is protective in appropriate contexts, so lower inflammatory activity is not automatically better in every person or situation.
Blood markers can indicate systemic inflammatory activity but do not identify one source, mechanism, or tissue. [2]

Inflammation coordinates defence, containment, repair, and adaptation. Acute inflammation is usually time-limited and organized around a defined challenge. Inflammaging refers instead to a chronic inflammatory tendency that can emerge from many weak or recurring inputs across the body. The expanded hallmarks framework treats chronic inflammation as a hallmark because it both reflects and influences other ageing mechanisms. [1] [4]

Acute Inflammation and Inflammaging

Feature	Acute Response	Inflammaging
Typical trigger	Infection, injury, or short-lived challenge	Multiple endogenous, environmental, and persistent inputs
Time course	Rapid activation followed by resolution	Long-term, fluctuating, and often low-grade
Main value	Defence and repair	No single adaptive purpose; may reflect accumulated dysregulation
Measurement	Clinical context plus local and systemic markers	Repeated patterns across markers, tissues, and health context

Where the Signals Can Come From

Damage-associated molecules released by stressed or dying cells
Senescence-associated secretory signalling
Mitochondrial dysfunction and misplaced mitochondrial DNA
Altered gut or epithelial barrier function
Changes in immune-cell composition and regulation
Persistent infection, adipose inflammation, or chronic disease

These contributors can reinforce one another, which makes inflammaging a network property rather than a single cytokine pathway. [1] [2] [3]

Relationship to Immunosenescence

Immunosenescence describes age-associated changes in immune composition and function, including altered responses to new antigens and changes in surveillance. Inflammaging describes persistent inflammatory activity. The two overlap and can reinforce each other, but reduced immune responsiveness and excessive inflammatory signalling are not the same phenomenon. [3]

Human Variation Matters

Inflammatory trajectories vary with infection history, environment, body composition, chronic disease, medication, ancestry, and social conditions. Older age does not produce one universal cytokine profile. Cross-sectional differences can also reflect disease burden rather than ageing itself, so longitudinal and population-diverse research is important. [2] [5]

Evidence Quality and Interpretation

Observational evidence consistently links several inflammatory markers with morbidity, frailty, and mortality risk, while mechanistic research identifies plausible feedback loops with other hallmarks. However, association does not show that one marker is causal or that suppressing it will improve every outcome. Anti-inflammatory interventions can also impair host defence or tissue repair, making pathway, timing, and population essential to interpretation. [2] [3]

What This Does Not Mean

It does not mean all inflammation is harmful.
It does not mean one elevated blood marker diagnoses inflammaging.
It does not mean systemic inflammation and neuroinflammation are interchangeable.
It does not mean inflammation is the single upstream cause of ageing.

References

López-Otín, C. et al. “Hallmarks of aging: An expanding universe.” Cell (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10809922/
Furman, D. et al. “Chronic inflammation in the etiology of disease across the life span.” Nature Medicine (2019). https://www.nature.com/articles/s41591-019-0675-0
Ferrucci, L. & Fabbri, E. “Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty.” Nature Reviews Cardiology (2018). https://www.nature.com/articles/s41569-018-0064-2
Franceschi, C. et al. “Inflammaging: a new immune–metabolic viewpoint for age-related diseases.” Nature Reviews Endocrinology (2018). https://www.nature.com/articles/s41574-018-0059-4
Terekhova, M. & Artyomov, M. “Rethinking inflammaging across human diversity.” Nature Aging (2025). https://www.nature.com/articles/s43587-025-00933-y