While short-term inflammation is useful and necessary, such as in the response to infection or injury, that same inflammatory signaling sustained over the long term becomes harmful. It becomes disruptive to tissue structure and function, altering the behavior of cells in damaging ways. Chronic inflammation is a feature of aging, and clearly contributes to the onset and progression of all of the common age-related conditions. It seems unlikely that age-related chronic inflammation can be effectively prevented, other than by removing the various forms of underlying cell and tissue damage that provoke continual maladaptive inflammatory responses. While one can suppress specific inflammatory signals in blunt ways, that only affects some inflammation, and also suppresses the normal, short-term inflammation necessary for defense against pathogens and regeneration from injury.
The relationship between aging and peripheral inflammation represents a complex and multifactorial process, with many molecular mechanisms contributing to a prolonged state of chronic low-grade inflammation, also called inflammaging. In contrast to acute inflammation, which is a transient response to infection or injury, inflammaging is a persistent, low-grade inflammatory state that develops as a result of the combined influence of internal and external factors accumulated throughout life. This process is characterized by sustained immune pathway activation, the increased production of pro-inflammatory cytokines, and the dysregulation of immune homeostasis, all of which contribute to the progressive functional decline associated with aging.
Aging affects multiple peripheral organs, including the liver, adipose tissue, skeletal muscles, and gastrointestinal tract, all of which play a crucial role in modulating systemic inflammation. The progressive dysfunction of these organs with age is primarily caused by molecular and cellular alterations, including oxidative stress, genomic instability, epigenetic changes, mitochondrial impairment, and cellular senescence. All of these create an inflammatory microenvironment that evokes tissue damage, ultimately contributing to the onset and progression of many age-related diseases, including cardiovascular disorders, neurodegenerative conditions, and cancer. At the molecular level, inflammaging involves a complex network of inflammatory mediators, including cytokines, acute-phase proteins, and damage-associated molecular patterns (DAMPs), which activate various intracellular signaling pathways.
A defining feature of inflammaging is the senescence-associated secretory phenotype (SASP). As aging occurs, senescent cells accumulate in several tissues, promoting a pro-inflammatory environment that supports immune system activation and drives tissue remodeling. An additional factor in inflammaging is gut microbiota dysbiosis, which has become increasingly recognized as a significant regulator of systemic inflammation in aging individuals. Age-related alterations in gut microbiota composition can result in increased intestinal permeability, facilitating the translocation of bacterial endotoxins, such as lipopolysaccharide (LPS), into the circulation. This process triggers sustained immune cell activation, further enhancing systemic inflammation.
Link: https://doi.org/10.3390/biom15030404
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