40 SKIN INFLAMMAGING
low-level inflammation associated with ageing, termed inflammaging. This is characterized by increased levels of circulating proinflammatory cytokines and a shift toward cellular senescence, changes that are believed to drive many age-associated conditions.
Causes of inflammaging Emerging research has identified several key drivers of inflammaging, which collectively contribute to cellular senescence, chronic low- grade inflammation, and functional decline in ageing tissues. The four major factors implicated are:
Compromised barrier integrity due to stress Psychological, metabolic, and environmental stressors can disrupt epithelial and endothelial barriers (eg gut epithelium, blood-brain barrier, skin), leading to translocation of microbial products (such as lipopolysaccharides) and activation of pattern recognition receptors (PRRs). This process triggers innate immune responses, fuelling persistent low-grade inflammation and accelerating tissue ageing.
Oxidative stress Accumulation of reactive oxygen species (ROS) from mitochondrial dysfunction, environmental insults, and chronic metabolic activity leads to oxidative damage of proteins, lipids, and DNA. This activates NF-κB and other pro- inflammatory transcription factors, perpetuating a cycle of inflammation and cellular senescence.
Cytokine dysregulation Cytokines, small signaling proteins secreted by immune and non-immune cells, are central to immune homeostasis. A balanced cytokine network supports tissue repair and regeneration, but with aging, cytokine secretion profiles shift toward a pro- inflammatory phenotype—a phenomenon referred to as ‘inflammaging cytokine signature’. Key cytokines implicated include tumour
necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Elevated
A IL-34 Young Skin IL-34 IL-34 IL-34 IL-34 IL-34 Aged Skin
Healthy M1/M2 balance
Young fibroblast Senescent fibroblast
M2 macrophage M1 macrophage
Figure 2: Imbalance of macrophages leading to inflammaging
systemic levels of these cytokines are considered biomarkers of inflammaging, correlating with frailty, immune dysregulation, sarcopenia, and increased morbidity and mortality.5,7,10
Inflammatory cascade activation Continuous activation of the innate immune system—through Toll-like receptors (TLRs), complement pathways, and inflammasomes— leads to sustained production of chemokines, prostaglandins, and matrix-degrading enzymes. This cascade contributes to chronic tissue remodeling, immune cell infiltration, and feed-forward amplification of inflammation. However, out of these factors, cytokines are
topic of focus for research. Currently, cytokines are used as biomarkers of inflammaging as they are indicative of inflammation and play a large role in the regulation of pro- and anti- inflammatory immune regulation.5 Cytokines are small proteins that are secreted by many cell types that are very
B
relevant in the study of ageing and longevity. Ageing studies show that a healthy balance of pro- and anti-inflammatory cytokine secretion is associated with successful ageing, whereas dysregulation of this system results in inflammaging, poor ageing phenotypes, and other ageing related diseases.7 Currently, levels of TNF-a, IL-6 and IL-1
can be used as inflammatory biomarkers that indicate frailty, an altered immune system, functional decline and mortality associated with inflammaging.10
Cytokines as biomarkers and therapeutic targets Among these four drivers, cytokine signaling has been the primary focus of current research. Cytokines act as both mediators and biomarkers of inflammaging, making them valuable tools for assessing biological age and predicting age-related disease risk. Elevated IL-6 levels, for example, are strongly associated with cardiovascular events,
Skewing in M1/M2 balance Collagen
Figure 3: A model proposed to explain the mechanism of inflammaging in skin PERSONAL CARE November 2025
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