Inflammaging: a new immune–metabolic viewpoint for age-related diseases

C Franceschi, P Garagnani, P Parini… - Nature Reviews …, 2018 - nature.com
Nature Reviews Endocrinology, 2018nature.com
Ageing and age-related diseases share some basic mechanistic pillars that largely
converge on inflammation. During ageing, chronic, sterile, low-grade inflammation—called
inflammaging—develops, which contributes to the pathogenesis of age-related diseases.
From an evolutionary perspective, a variety of stimuli sustain inflammaging, including
pathogens (non-self), endogenous cell debris and misplaced molecules (self) and nutrients
and gut microbiota (quasi-self). A limited number of receptors, whose degeneracy allows …
Abstract
Ageing and age-related diseases share some basic mechanistic pillars that largely converge on inflammation. During ageing, chronic, sterile, low-grade inflammation — called inflammaging — develops, which contributes to the pathogenesis of age-related diseases. From an evolutionary perspective, a variety of stimuli sustain inflammaging, including pathogens (non-self), endogenous cell debris and misplaced molecules (self) and nutrients and gut microbiota (quasi-self). A limited number of receptors, whose degeneracy allows them to recognize many signals and to activate the innate immune responses, sense these stimuli. In this situation, metaflammation (the metabolic inflammation accompanying metabolic diseases) is thought to be the form of chronic inflammation that is driven by nutrient excess or overnutrition; metaflammation is characterized by the same mechanisms underpinning inflammaging. The gut microbiota has a central role in both metaflammation and inflammaging owing to its ability to release inflammatory products, contribute to circadian rhythms and crosstalk with other organs and systems. We argue that chronic diseases are not only the result of ageing and inflammaging; these diseases also accelerate the ageing process and can be considered a manifestation of accelerated ageing. Finally, we propose the use of new biomarkers (DNA methylation, glycomics, metabolomics and lipidomics) that are capable of assessing biological versus chronological age in metabolic diseases.
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