Oxford Textbook of Geriatric Medicine 4e: Chapter 13- Age-related physiological changes and ageing phenotypes

Ageing is characterised by progressive morphological and functional changes that occur in parallel across multiple organs and systems as the dynamic equilibrium between damage accumulation and resilience mechanisms shifts toward more unopposed damage. Ageing-related changes can be conceptualised using a hierarchical model with three levels: 1) biological ageing, including all the changes occurring at molecular, cellular, and intercellular levels, in particular those biological mechanisms aimed at maintaining cellular health that have been called “hallmarks of ageing” (e.g. change in function of immune cells toward a pro-inflammatory state, reduced mitochondrial oxidative capacity, genomic instability due to somatic mutation and unrepaired DNA mutation events, epigenetic alterations that modify gene expression patterns and response and may challenge cell identity); phenotypic ageing, including the interrelated changes occurring in four domains, namely homeostatic dysregulation at the root of metabolic diseases, body composition changes with expansion of adipose tissue, shrinking of muscle and change in their composition and intercellular matrix modification that involves almost every tissue and organ, energetics imbalance between energy availability and demand and loss of neuronal function/plasticity. These changes, when they are overt, emerge as chronic diseases and multimorbidity in all ageing individuals, although with great heterogeneity in the population. Altogether, these changes cause functional ageing, which is comprehensive of age-associated decline in physical, cognitive, emotional, and social functions, leading to adverse outcomes, such as disability, loss of independence, and death.