Inflammageing, a portmanteau of inflammation and aging, is a state of chronic, low-grade, sterile, systemic inflammation that develops with advancing chronological age. This pervasive elevation of pro-inflammatory markers, such as C-reactive protein (CRP) and Interleukin-6 (IL-6), is a highly significant risk factor for age-related morbidity and mortality. It is considered a fundamental driver of the aging process itself, contributing to frailty, metabolic dysfunction, and nearly all chronic diseases. The condition is distinct because it persists without an overt, acute infection.
Origin
The term was first coined in 2000 by Professor Claudio Franceschi, an Italian immunologist, to encapsulate the complex, systemic nature of age-related immune changes. It emerged from the observation that older individuals consistently exhibit higher basal levels of circulating inflammatory biomarkers, even in the absence of obvious pathology. This conceptualization shifted the scientific focus from aging as a purely passive decline to an active, regulated, and potentially modifiable inflammatory process. It integrates the fields of immunology, endocrinology, and gerontology.
Mechanism
The mechanism is multifactorial and involves a breakdown of homeostatic control over the innate immune system, coupled with cellular damage accumulation. Key contributors include cellular senescence, where senescent cells release a pro-inflammatory senescence-associated secretory phenotype (SASP), and mitochondrial dysfunction, which generates excessive reactive oxygen species (ROS). Additionally, age-related changes in the gut microbiome and increased gut permeability allow bacterial products to leak into the circulation, activating inflammatory pathways like the NLRP3 inflammasome. These converging molecular pathways sustain the chronic, low-grade inflammatory environment that accelerates biological aging across all organ systems.
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