Immune system undergoes profound changes during ageing. Adaptive immune response becomes less effective as lymphocyte numbers are reduced in the elderly. This is the result of the decline of generation of new naive T lymphocytes as a consequence of thymic involution. Furthermore, as we age T-lymphocyte population comprises more and more of memory cells at the expense of naive cells. 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 was termed as inflamm-aging. Inflamm-aging 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. 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.
Causes
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. Senescent cells increase with aging, and senescent cells secrete a pro-inflammatory cocktail of chemicals, a condition known as senescence-associated secretory phenotype. 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 epithlial barrier, and chronic stress occurring in any stage of the individual's life. Cytokines with inflammatory properties can also be secreted by fat tissue.
Proposed interventions
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
