Inflammaging: Chronic Inflammation as a Core Driver of Ageing
What Is Inflammaging?
Inflammaging refers to the chronic, low-grade inflammation that develops with age, even in the absence of infection or acute illness¹.
Unlike short-term inflammation—which is protective and necessary for healing—inflammaging is persistent and dysregulated, gradually damaging tissues and impairing cellular function.
It is now considered one of the central mechanisms linking ageing to chronic diseases, including cardiovascular disease, metabolic dysfunction, neurodegeneration, and immune decline¹².
The Role of Inflammation in the Body
Inflammation is a fundamental biological response designed to:
- Eliminate pathogens
- Repair damaged tissue
- Restore homeostasis
In acute situations, this process is tightly controlled and resolves once the threat is removed.
However, with ageing, this regulatory balance becomes impaired, leading to a state of chronic activation without proper resolution².
What Causes Inflammaging?
Inflammaging does not arise from a single source, but from multiple overlapping processes that reinforce each other over time.
1. Accumulation of Senescent Cells
Senescent cells accumulate with age and secrete pro-inflammatory molecules through the senescence-associated secretory phenotype (SASP).
These include cytokines, chemokines, and proteases that promote chronic inflammation and disrupt surrounding tissue function³.
2. Mitochondrial Dysfunction and RONS
Age-related mitochondrial decline leads to increased production of reactive oxygen and nitrogen species (RONS).
These molecules can trigger inflammatory signaling pathways and activate immune responses even in the absence of infection⁴.
3. Immune System Dysregulation
With age, the immune system undergoes functional changes:
- Reduced ability to clear damaged cells
- Increased baseline inflammatory signaling
- Impaired resolution of inflammation
This contributes to a persistent inflammatory environment⁵.
4. Increased CD38 Activity and NAD⁺ Decline
Inflammation itself drives expression of CD38, an enzyme that degrades NAD⁺.
As NAD⁺ levels decline, cellular repair systems weaken, further increasing stress and inflammatory signaling⁶.
5. Gut Barrier Dysfunction
Changes in gut integrity and microbiome composition with age can allow inflammatory molecules (such as lipopolysaccharides) to enter circulation
This contributes to systemic inflammation and immune activation⁷
How Inflammaging Drives Ageing
Chronic inflammation affects nearly every major biological system:
Cellular Damage
Persistent inflammatory signaling increases oxidative stress and contributes to damage of DNA, proteins, and lipids⁴.
Impaired Tissue Function
Inflammation disrupts normal tissue structure and reduces regenerative capacity, contributing to organ decline³.
Metabolic Dysfunction
Inflammaging is strongly linked to insulin resistance, altered lipid metabolism, and reduced mitochondrial efficiency⁸.
Neurodegeneration
Chronic inflammation in the brain contributes to neuronal damage and is associated with diseases such as Alzheimer’s and Parkinson’s¹.
Inflammaging and Longevity
Inflammaging is not just a consequence of ageing—it actively accelerates it
It sits at the intersection of multiple longevity pathways:
- NAD⁺ metabolism (via CD38 activation)
- Mitochondrial function (via oxidative stress)
- Cellular senescence (via SASP signaling)
- Autophagy (via impaired cellular cleanup)
Because it amplifies damage across systems, inflammaging acts as a central driver of biological decline.
A Self-Reinforcing Cycle
Inflammaging is part of a feedback loop:
- Cellular damage increases inflammatory signaling
- Inflammation increases CD38 activity and NAD⁺ depletion
- Reduced NAD⁺ impairs repair systems
- Impaired repair increases cellular damage
Over time, this creates a persistent cycle of dysfunction.
Why Inflammaging Matters for Healthspan
Chronic inflammation is one of the strongest predictors of age-related disease and mortality.
Elevated inflammatory markers are associated with:
- Cardiovascular disease
- Type 2 diabetes
- Neurodegenerative disorders
- Frailty and functional decline¹²
Reducing chronic inflammation is therefore a key strategy for improving healthspan—not just lifespan.
Summary
Inflammaging describes the chronic, low-grade inflammation that develops with age and contributes to widespread biological decline
It arises from multiple interconnected processes, including senescent cell accumulation, mitochondrial dysfunction, immune dysregulation, and NAD⁺ depletion
Rather than being a single pathway, it acts as a central amplifier of ageing, accelerating damage across systems
Understanding and targeting inflammaging is essential for maintaining cellular function, reducing disease risk, and supporting long-term health.
Footnotes
1 Inflammaging and age-related disease https://pubmed.ncbi.nlm.nih.gov/29676998/
2 The role of inflammation in aging https://pubmed.ncbi.nlm.nih.gov/28188029/
3 Senescence-associated secretory phenotype (SASP) https://pubmed.ncbi.nlm.nih.gov/30726765/
4 Reactive oxygen species and inflammation https://pubmed.ncbi.nlm.nih.gov/27252401/
5 Immune system aging and chronic inflammation https://pubmed.ncbi.nlm.nih.gov/31123340/
6 CD38 and NAD⁺ metabolism in aging https://pubmed.ncbi.nlm.nih.gov/27463679/
7 Gut microbiome and inflammation in aging https://pubmed.ncbi.nlm.nih.gov/29676997/
8 Inflammation and metabolic dysfunction https://pubmed.ncbi.nlm.nih.gov/31088896/
