The Immune System in the Elderly: A Fair Fight Against Diseases?

Anis Larbi; Paulina Rymkiewicz; Anusha Vasudev; Ivy Low; Nurhidaya Binte Shadan; Seri Mustafah; Shamini Ayyadhury; Tamas Fulop

Disclosures

Aging Health. 2013;9(1):35-47. 

In This Article

Inflammation & Aging

Inflammation is a tightly regulated process that ensures recruitment of competent cells and regulation of their functions for the clearance of pathogens. The actors of inflammation are cytokines, chemokines, adipokines, soluble mediators of inflammation and acute phase proteins, among others. The duration, intensity and variety of its components will determine the impact of inflammation on the immune response. An unbalance in this tightly regulated process may lead to significant consequences. Not only immune cells, but endothelial cells, fibroblasts and keratinocytes, among other cell types, are able to produce these mediators and are partners and players of the immune responses and fully involved in the inflammatory process.

Inflammation is a normal process that may be exacerbated if not properly regulated in response to antigen recognition, or become chronic in the case of persisting condition(s) in the elderly, including infections such as CMV. Persistent infection is a major issue for the immune system as it requires lifelong immunosurveillance and dedicated resources. Inflammation in aging is often referred to as low-grade inflammation.[68] A set of proinflammatory mediators in aging such as RANTES, MIP-1α, IL-8, MCP-1, IL-6 and TNF-α have been identified. These inflammatory mediators were associated with atherosclerosis, dementia and diabetes, amongst other age-associated diseases. Not only is the presence of these markers in high quantities linked to comorbidities, but also to mortality.[69] An important set of markers associated with comorbidities and mortality is IL-6, TNF-α and CRP. Many mechanisms influence how inflammation is resolved and many events will induce such inflammation.[70] Pathogens requiring life-long control can be viruses (HIV, CMV), bacteria (Helicobacter pylori and Mycobacterium tuberculosis) or parasites (Plasmodium falciparum and Toxoplasma gondii). H. pylori, even after resolution of infection, is still associated with increased susceptibility of gastric cancers, suggesting that the inflammation initiated has long-lasting and probably irreversible effects.[71] While a HIV pandemic may be stopped and H. pylori infection prevented, most individuals will encounter CMV during their life. One of the most relevant studies on the relationship between CMV seropositivity and mortality was performed recently and showed that independent of age CMV seropositivity was statistically significantly associated with all-cause mortality.[72] Those with high CRP levels showed a 30% higher risk for all-cause and cardiovascular diseases mortality compared with those with low CRP levels. This clearly suggested the association between proinflammatory profiles, morbidities and mortality in elderly with persistent infections. One should nonetheless be cautious with overinterpreting such studies, as CMV is less prevalent in certain populations and the elderly still present signs of immune senescence. One should consider the possibility that other persistent stimulations (by self- and nonself-antigens) may drive similar phenomenon, or that aging per se has the same effect.

On the clinical side, the levels of proinflammatory molecules were associated with diseases and often used as markers for comorbidities and predictors of mortality.[69] Among these, CRP, IL-6 and TNF-α often appear to be associated with comorbidities such as cardiovascular diseases, atherosclerosis, dementia and diabetes. These association studies did not enable to predict disease onset in the elderly at the inflammatory level. Furthermore, studies have shown that higher levels of proinflammatory molecules are not always associated with poor health, since centenarians display higher IL-6 levels.[73] This suggests that inflammation in aging is probably a sign of unsuccessful aging associated with diseases rather that a general phenomenon occurring in all elderly individuals.

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