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

Abstract

open5siThis work was partly supported by Fondazione Cassa di Risparmio delle Province Lombarde (CARIPLO) (Rif. 2015–0564 to C.F. and Rif. 2016–0835); European Union (EU) FP7 Project HUMAN (Health and the Understanding of Metabolism, Aging and Nutrition) (grant agreement 602757) and EU Joint Programme – Neurodegenerative Disease Research (JPND) Adage to C.F.; EU H2020 Project PROPAG-AGEING (grant agreement 634821) to C.F. and P.G.; the Italian Ministry of Health Ricerca Finalizzata Young Researchers (under 40)–Giovani Ricercatori (GR-2013-02358026) to A.S.; Basic Research Projects of the Alma Mater Studiorum - University of Bologna (ALMA-IDEA-2017) to C.G.; and a grant of the Ministry of Education and Science of the Russian Federation (agreement 074-02-2018-330) "Digitalized and Personalized Medicine of Healthy Aging (DPM-AGEING)" at Lobachevsky State University of Nizhny Novgorod to C.FAgeing 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.openopenFranceschi C.; Garagnani P.; Parini P.; Giuliani C.; Santoro A.Franceschi C.; Garagnani P.; Parini P.; Giuliani C.; Santoro A