Miller Zachary, Twardowski Laura-Marie, Reader Brenda F, Rojas Mauricio, Lehmann Mareike, Mora Ana L
Department of Internal Medicine, Division of Pulmonary Critical Care and Sleep Medicine, Davis Heart Lung Research Institute, The Ohio State University, Columbus, OH, USA.
Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.
Eur Respir Rev. 2025 Jul 23;34(177). doi: 10.1183/16000617.0233-2024. Print 2025 Jul.
Ageing significantly impacts lung function and increases susceptibility to chronic lung diseases. The lung is a complex organ with multiple cell types that undergo cellular age-related perturbations or hallmarks. As knowledge of ageing mechanisms has progressed, we have a better understanding how intracellular adaptations impact cellular crosstalk and integrate to increase the susceptibility to age-related diseases in the lung. Herein, we discuss the prospects of exhaustion of lung progenitor cells, disrupted lung cell plasticity, perturbation in fibroblasts, impaired adaptive immune responses and alterations in lung microenvironment in the promotion of ageing and age-related lung diseases. Additionally, the ageing process trajectory of the lung depends on a combination of biological, genetic, metabolic, biomechanical and sociobehavioural factors that range from protective phenotypes to accelerated ageing phenotypes. We propose the concept of AgEnOmics, which expands the temporal dimension of lung ageing by distinguishing between chronological ageing and accelerated lung ageing phenotypes. Based on this concept, we define biomarkers of biological ageing that will help to define accelerated ageing and early interventions in biological ageing-related lung diseases.
衰老对肺功能有显著影响,并增加患慢性肺病的易感性。肺是一个复杂的器官,有多种细胞类型,这些细胞会经历与年龄相关的细胞扰动或特征。随着对衰老机制认识的进展,我们对细胞内适应性如何影响细胞间相互作用并整合以增加肺部对与年龄相关疾病的易感性有了更好的理解。在此,我们讨论肺祖细胞耗竭、肺细胞可塑性破坏、成纤维细胞扰动、适应性免疫反应受损以及肺微环境改变在促进衰老和与年龄相关的肺部疾病中的前景。此外,肺的衰老过程轨迹取决于生物、遗传、代谢、生物力学和社会行为等多种因素的综合作用,这些因素涵盖从保护性表型到加速衰老表型。我们提出了“AgEnOmics”的概念,通过区分实际年龄衰老和加速肺衰老表型来扩展肺衰老的时间维度。基于这一概念,我们定义了生物衰老的生物标志物,这将有助于定义加速衰老以及对与生物衰老相关的肺部疾病进行早期干预。