Review
Proinflammatory Cytokines, Aging, and Age-Related Diseases

https://doi.org/10.1016/j.jamda.2013.05.009Get rights and content

Abstract

Inflammation is a physiological process that repairs tissues in response to endogenous or exogenous aggressions. Nevertheless, a chronic state of inflammation may have detrimental consequences. Aging is associated with increased levels of circulating cytokines and proinflammatory markers. Aged-related changes in the immune system, known as immunosenescence, and increased secretion of cytokines by adipose tissue, represent the major causes of chronic inflammation. This phenomenon is known as “inflamm-aging.” High levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α, and C-reactive protein are associated in the older subject with increased risk of morbidity and mortality. In particular, cohort studies have indicated TNF-α and IL-6 levels as markers of frailty. The low-grade inflammation characterizing the aging process notably concurs at the pathophysiological mechanisms underlying sarcopenia. In addition, proinflammatory cytokines (through a variety of mechanisms, such as platelet activation and endothelial activation) may play a major role in the risk of cardiovascular events. Dysregulation of the inflammatory pathway may also affect the central nervous system and be involved in the pathophysiological mechanisms of neurodegenerative disorders (eg, Alzheimer disease).The aim of the present review was to summarize different targets of the activity of proinflammatory cytokines implicated in the risk of pathological aging.

Section snippets

Immunosenescence

Immunosenescence is a progressive modification of the immune system that leads to greater susceptibility to infections, neoplasias, and autoimmune manifestations. This phenomenon is mainly due to prolonged antigenic stimulation across the life span.8 The main alteration responsible for immunosenescence concerns the functioning of T cells.9 Consequences of the thymic involution occurring with aging are decreases of the regulatory T lymphocytes and naïve T lymphocytes (in favor of memory T

Cytokines, Morbidity, and Mortality

Elevated levels of TNF-α, IL-6, and CRP are correlated with an increased risk of morbidity and mortality (all causes together), not only in a frail population (defined according to Fried et al's criteria38) but also in independent, nonfrail elderly.39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 The effects of cytokine dysregulation are independent of the other usual mortality risk factors (tobacco use, diabetes, arterial hypertension, hypercholesterolemia) and comorbid conditions.40, 42, 45, 46, 50

Cytokines and Frailty

Conclusion

Aging is accompanied by immune, hormonal, and adipose changes leading to a chronic inflammatory state. Levels of proinflammatory cytokines, principally TNF-α and IL-6, have damaging effects on aging (Table 1). They influence the onset of frailty, cognitive decline, and cardiological, neurological, and vascular events. They are also closely linked to the genesis of cancers, with cardiac remodeling in heart failure, and so forth. The limitations of this review arise from the numerous

Acknowledgments

The authors thank Dr Christian Michaud and Marie Josée Michaud (Sables d'Olonne, France).

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    The authors declare no conflicts of interest.

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