Chronic Inflammation in Immune Aging: Role of Pattern Recognition Receptor Crosstalk with the Telomere Complex?

Abstract

Age-related decline in immunity is characterized by stem cell exhaustion, telomere shortening, and disruption of cell-to-cell communication, leading to increased patient risk of disease. Recent data have demonstrated that chronic inflammation exerts a strong influence on immune aging and is closely correlated with telomere length in a range of major pathologies. The current review discusses the impact of inflammation on immune aging, the likely molecular mediators of this process, and the various disease states that have been linked with immunosenescence. Emerging findings implicate NF-κB, the major driver of inflammatory signaling, in several processes that regulate telomere maintenance and/or telomerase activity. While prolonged triggering of pattern recognition receptors is now known to promote immunosenescence, it remains unclear how this process is linked with the telomere complex or telomerase activity. Indeed, enzymatic control of telomere length has been studied for many decades, but alternative roles of telomerase and potential influences on inflammatory responses are only now beginning to emerge. Crosstalk between these pathways may prove to be a key molecular mechanism of immunosenescence. Understanding how components of immune aging interact and modify host protection against pathogens and tumors will be essential for the design of new vaccines and therapies for a wide range of clinical scenarios.

Lung cellular senescence is independent of aging in a mouse model of COPD/emphysema

“…Some of the cytokines attract cells of the innate immune system (such as neutrophils, macrophages, and dendritic cells) and result in a persistent inflammatory response in COPD 52 , 53 . Earlier evidence shows a close relationship between the activation of PRR pathways and inflammaging 54 – 56 . However, it remains unclear how DAMPs markers play a vital role during aging and aging-associated chronic inflammatory lung diseases.…”

C-Reactive Protein Impairs Dendritic Cell Development, Maturation, and Function: Implications for Peripheral Tolerance

“…( 37 )]. Indeed, some of the prominent features of immunosenescence are inflammation, decreased T cell numbers, and decreased naïve and memory T cell responsiveness ( 37 , 38 , 39 ), and in the aged, inflammaging can contribute to dysregulated DC responses and a consequent breakdown of tolerance that can predispose them to autoimmunity ( 40 , 41 ). We propose that in this context, modest elevation of CRP due to biological aging ( 12 ) might act as a tonic suppressor of DC activation and thus limit auto-reactivity.…”

The association between longer relative leukocyte telomere length and risk of glioma is independent of the potentially confounding factors allergy, BMI, and smoking

“…Consequently, blood samples from the patients were drawn at a time when medical treatment, stress, and inflammatory conditions may have had an effect on rLTL in peripheral blood. But, since stress and inflammatory conditions are expected to shorten telomere length in patients [41], these confounding factors would not affect the association between longer telomere length and glioma risk.…”