Inflammation and chronic diseases

Cell aging:

The process of cell aging includes an arrest of cell proliferation and increased secretion of pro-inflammatory cytokines/chemokines. Age-dependent alterations in cellular pathways cause a decline in organ inflammation and chronic disease progression. Aging enables chronic diseases, and causes much organ damage before the diagnosis of disease.

Chronic inflammation:

Systemic chronic inflammation (SCI) includes the activation of immune components that are distinct from those formed during acute immune response. An acute response usually happens during infection or injury. SCI can impair normal immune function, increasing susceptibility to infections, tumors and poor response to vaccines.

Chronic infections (viruses, bacteria, other microbes) appear to cause SCI, but are not likely the primary drivers of SCI. A certain group of population listed below have low rates of inflammation and chronic disease and inflammatory markers which do not increase with age: hunters of Ecuadorian amazon or Tanzania, horticulturalists of Bolivia or Papua new guinea and agricultarists from rural Ghana. These communities are unexposed to industrialized environments but exposed to a variety of microbes.

SCI and risk of NCDs:

SCI increases with age, and older individuals have higher circulating levels of cytokines. chemokines and acute phase proteins (if not all), as well as greater expression of genes involved in inflammation. SCI is low grade and persistent, and causes collateral damage to tissues and organs, such as by inducing oxidative stress. Evidence is strong for the association of SCI with metabolic syndrome, type 2 diabetes, and CVD.

Lifestyle, social and physical environment:

The human circadian rhythm needs to be closely synchronized with diurnal fluctuations. As a result of industrialization, an evolutionary mismatch has happened in humans due to their separation from the ecological niche, which is an important cause of SCI. Physical inactivity increases the risk of age-related diseases and mortality. High glycemic load foods, trans fatty acids, and dietary salt cause oxidative stress which activates the inflammatory genes. Changes in the gut microbiota influence the outcome of multiple inflammatory pathways.

Stressors and toxicants:

Social interactions and sleep quality can promote SCI and insulin resistance. Increased exposure to artificial light, especially blue spectrum, at atypical biologic times causes disruption of circadian rhythm, which in-turn promotes inflammation, for eg: night shift work increases risk for metabolic syndrome. Xenobiotics, air pollutants, industrial chemicals, and hazardous waste products promote SCI.

Reference:

1. Furman D, Campisi J, Verdin E et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25(12):1822-32.

2. Mkrtchyan G.V, Abdelmohsen K, Andreux P et al. ARDD 2020: from aging mechanisms to interventions. Aging. 2000;12:24.