Physics

Internal medicine

Microbiome

Neuroscience

Ageing

Bioinformatics

Biology

Optics

Crosstalk

Immunology

Inflammation

Immunosenescence

Medicine

Immune system

Nature Reviews Endocrinology

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. Many mechanistic processes during ageing and age-related diseases cause inflammation. In this Review, the authors discuss the relationship between the immune and metabolic systems during ageing and age-related diseases and the potential use of new biomarkers capable of distinguishing between biological and chronological age in metabolic diseases.

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