Background: Individuals with bipolar disorder have a reduced life expectancy and may experience accelerated biological ageing. In individuals with bipolar disorder and healthy controls, we examined differences in age-related changes in physiology. Methods: UK Biobank recruited more than 500,000 participants, aged 37–73, between 2006 and 2010. Generalised additive models were used to examine associations between age and grip strength, cardiovascular function, body composition, lung function and heel bone mineral density. Results: The main dataset included 271,118 adults (mean age = 56.04 years; 49.60% females). We found statistically significant differences between cases and controls for grip strength, blood pressure, pulse rate and body composition, with standardised mean differences of up to -0.24 (95% CI -0.28 to -0.19). Evidence of differences in lung function, heel bone mineral density or arterial stiffness was limited. Case-control differences were most evident for age-related changes in cardiovascular function (both sexes) and body composition (females). Differences did not uniformly narrow or widen with age and differed by sex. For example, the difference in systolic blood pressure between male cases and controls was -1.3 mmHg at age 50 and widened to -4.7 mmHg at age 65. Diastolic blood pressure in female cases was 1.2 mmHg higher at age 40 and -1.2 mmHg lower at age 65. Limitations: Analyses did not distinguish between bipolar disorder subtypes. Results may not generalise to other age groups. Conclusions: Differences between bipolar disorder cases and controls were most evident for cardiovascular and body composition measures. Targeted screening for cardiovascular and metabolic health in middle age is warranted to potentially mitigate excess mortality.