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Inflamm-ageing, defined as the chronic low-grade inflammation typical of ageing, seems to be the common biological factor responsible for the decline and the onset of disease in the elderly. The major age-related diseases share a common inflammatory pathogenesis, giving rise to the so-called ‘diseasome of inflamm-ageing’. Main objective of this review is to provide a comprehensive view of the complex interactions responsible for inflamm-ageing, underlining its relationship with metaflammation and the role of senescent cells, gut microbiota and nutrition in determining when, where and how much this phenomenon impacts on the health status during human lifespan.The ageing process and the health status of elderly people may be improved by facing and slowing down inflamm-ageing. Among the inflammation modulators, gut microbiota and nutrition should be exploited as potential powerful tools to promote healthy ageing and to extend the lifespan in humans.The possibility to control inflamm-ageing represents a powerful tool to modulate and counteract the major age-related pathologies and it is urgent to clarify the shady areas of the complex mechanisms underpinning inflamm-ageing in order to carry out targeted therapeutic interventions towards an improvement of the health status in the elderly population.