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.

Key points

  • According to geroscience, inflammation is one of the seven evolutionarily conserved mechanistic pillars of ageing that are shared by age-related diseases, including metabolic diseases.
  • Inflammaging is the long-term result of the chronic physiological stimulation of the innate immune system, which can become damaging during ageing — a period of life largely unpredicted by evolution.
  • Inflammaging is the by-product of the degeneracy of a few receptors that can sense a variety of non-self, self and quasi-self damage signals (or ‘garbage’) and activate the innate immune system.
  • Inflammaging and metaflammation largely share the same molecular mechanisms, in which metaflammation can be conceptualized as a specific situation of chronic inflammation caused by nutrient excess.
  • The gut microbiota has a central role in metaflammation and inflammaging, as it can release inflammatory products and contribute to the circadian rhythms and crosstalk with other organs and systems.
  • Biomarkers of biological age, such as DNA methylation, glycomics, metabolomics and lipidomics, can be successfully applied to metabolic diseases.