Chronic low-grade inflammatory phenotype: clinical significance, causal factors and approaches to therapy

CLIP is a chronic, systemic and smoldering inflammatory condition clearly indicated by a 2–4-fold increase in serum levels of inflammatory mediators such as interleukin-6 and C-reactive protein. Many other cellular and molecular mediators of inflammation are also involved in the development of CLIP. CLIP typically occurs in older people, hence also known as aging inflammation, and is an integral part of the aging spectrum of the immune system. Causal factors may include: persistent viral infections such as chronic cytomegalovirus infection; cellular aging and the inability, in this regard, to eliminate degraded materials and waste products; dysbiosis and impaired intestinal permeability, obesity and others. A significant body of evidence suggests that CLIP is a powerful contributor to senility and many other adverse health chronic conditions associated with aging. Many inflammatory mediators and their regulatory mechanisms in CLIP can serve as potential targets for therapeutic intervention. However, the complexity of the inflammatory network should be taken into account when developing new interventional strategies for the treatment of CLIP and associated chronic conditions. Non-pharmacological interventions such as caloric restriction and exercise have beneficial effects on CLIP and its causative factors, which in turn can provide significant health benefits. Metformin and resveratrol have anti-inflammatory properties and, in this regard, may serve as promising therapeutic agents for the treatment of chronic low-grade inflammation and frailty.