Age-related mechanisms in the context of rheumatic disease

Ageing is characterized by a progressive loss of cellular function that leads to a decline in tissue homeostasis, increased vulnerability and adverse health outcomes. Important advances in ageing research have now identified a set of nine candidate hallmarks that are generally considered to contribute to the ageing process and that together determine the ageing phenotype, which is the clinical manifestation of age-related dysfunction in chronic diseases. Although most rheumatic diseases are not yet considered to be age related, available evidence increasingly emphasizes the prevalence of ageing hallmarks in these chronic diseases. On the basis of the current evidence relating to the molecular and cellular ageing pathways involved in rheumatic diseases, we propose that these diseases share a number of features that are observed in ageing, and that they can therefore be considered to be diseases of premature or accelerated ageing. Although more data are needed to clarify whether accelerated ageing drives the development of rheumatic diseases or whether it results from the chronic inflammatory environment, central components of age-related pathways are currently being targeted in clinical trials and may provide a new avenue of therapeutic intervention for patients with rheumatic diseases. In this Review, the authors describe the involvement of characteristic hallmarks of ageing in rheumatic diseases, suggesting that these chronic conditions can be considered to be diseases of premature or accelerated ageing, in which anti-ageing drugs may have therapeutic benefits. Key points Rheumatic disease prevalence is increased as a consequence of population ageing. Rheumatic diseases share common ageing characteristics and molecular pathways, which enables their classification as premature-ageing or accelerated-ageing diseases. Ageing and inflammation form a self-perpetuating, vicious cycle to advance rheumatic disease in patients and accelerate ageing phenotypes. Anti-ageing drugs may have therapeutic potential for the management and treatment of patients with rheumatic disease.