Purpose of reviewLongevity with good health and long-term survival in space are two of the many challenges that scientists face in the twenty-first century. Ageing and life in space are both associated with undesirable effects on normal physiological processes. This review will outline how the endocrine, metabolic, immune and musculoskeletal systems are affected by microgravity and ageing, drawing analogies between the observed changes in an attempt to highlight common mechanisms.Recent findingsMild hypothyroidism, increased stress hormones (mainly catecholamines), decreased sex steroids, insulin resistance, impaired anabolic response to food intake, anorexia, altered mitochondrial function and systemic inflammatory response are common features of both ageing and microgravity. Both conditions lead to progressive bone and muscle atrophy, compromising mobility and the ability to perform essential daily tasks. In skeletal muscle, both ageing and space flight lead to weakness from whole muscle to single fibre level, accompanied by marked alterations in muscle architecture and in tendon mechanical properties.SummaryWhat makes microgravity an interesting and unique tool for gerontologists is that many space-related physiological changes resemble those observed during ageing, but are more or less quickly restored after re-entry, thus allowing the biology of ageing to be investigated both ways, not only during its development but also during recovery.