The ageing process is a progressive decrease in physiological function, caused by accruement of damage and misregulation in the cells and tissues of an organism. Human ageing has been the focus of much scientific investigation, but studies have been complicated by the variability of the process between subjects and the slow pace at which it occurs. Although the consequences of ageing on cellular biochemical signalling and metabolism have been well studied, the impact on the mechanical properties of cells and the extracellular matrix – and the mechanotransduction pathways that connect the two – have often been overlooked. In this review we will discuss recent advances in the fields of nuclear and cytoskeletal biophysics, and consider this work in the context of ageing. In particular, we will examine the role of the nucleus in cellular mechanotransduction and in ‘age-related diseases/phenomena’ such as progeria and cellular senescence. Finally, we will discuss the therapeutic options being explored, drawing attention to a new field of medicine termed ‘mechano-medicine’ that may prove useful in addressing age-related pathology.