The Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK.
Botnar Research Centre, NDORMS, University of Oxford, Oxford, UK.
Nat Rev Rheumatol. 2022 Dec;18(12):694-710. doi: 10.1038/s41584-022-00863-8. Epub 2022 Nov 3.
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.
衰老是指细胞功能的逐渐丧失,导致组织稳态失衡、脆弱性增加和不良健康结局。衰老研究的重要进展现在已经确定了一组九个候选衰老标志,这些标志通常被认为有助于衰老过程,并共同决定衰老表型,即慢性疾病中与年龄相关的功能障碍的临床表现。虽然大多数风湿性疾病目前还不被认为与年龄有关,但现有证据越来越强调这些慢性疾病中存在衰老标志。基于目前与风湿性疾病相关的分子和细胞衰老途径的证据,我们提出这些疾病具有许多在衰老中观察到的特征,因此可以被认为是过早或加速衰老的疾病。尽管需要更多的数据来阐明加速衰老是否驱动了风湿性疾病的发展,或者它是否是由慢性炎症环境引起的,但目前正在临床试验中针对与年龄相关的途径的核心成分进行靶向治疗,这可能为风湿性疾病患者提供新的治疗干预途径。