Inflamm-aging (also known as inflammaging or inflamm-ageing) is a chronic low-grade inflammation that develops with advanced age. It is believed to accelerate the process of biological aging and to worsen many age-related diseases.
The immune system declines as aging persists. This drastically affects an individual's adaptive immune system. With age, the number of lymphocytes being produced decreases, and the composition and quality of the mature lymphocyte pool changes.
While effectiveness of adaptive immune system declines, innate immune mechanisms become more active. This is represented by increased number of natural killer cells and increased production of pro-inflammatory cytokines. This chronic activation of innate immune system results in a low-grade chronic inflammation development in the elderly. This phenomenon is often referred to as inflammaging (inflamm-aging). Inflammaging is described as a low grade, chronic, controlled and asymptomatic inflammation which occurs in the absence of infection and is primarily driven by endogenous signals. Key molecules associated with inflamm-aging are elevated pro-inflammatory cytokines, especially IL-6, TNFα and C-reactive protein (CRP). This chronic inflamed state has detrimental effect on health and contributes to biological ageing and development of age-related pathologies. Inflamm-aging was shown to help development and worsen course of Alzheimer's disease, atherosclerosis, type II diabetes and chronic heart diseases.
As inflamm-aging is a complex and systemic issue, it is likely that inflammaging is a result of several factors. It seems that the major cause of inflamm-aging is accumulation of misplaced and misfolded self-molecules from damaged cells. These molecules are recognized by receptors of innate immune cells which leads to their activation and consequently to inflammation. Cell components which can stimulate innate cells include microRNAs, mitochondrial DNA or histones.
Inflamm-aging has been also associated with persistent Cytomegalovirus infection. Cytomegalovirus drives up production of a variety of inflammatory cytokines and also results in expansion of CMV specific memory T cells. Other possible factors that may lead to inflamm-aging include overnutrition, altered gut microbiome, impaired intestinal epithelial barrier, and chronic stress occurring in any stage of the individual's life. Cytokines with inflammatory properties can also be secreted by fat tissue.
Use of low-dose aspirin, exercise, and statins are therapies for inflammaging already in common use. Possible future therapies include senolytic drugs, probiotics, cytomegalovirus vaccine, and thymic replacement. or thymic rejuvenation
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