A well-functioning cardiovascular system is key in keeping lifelong health. Impairments to the cardiovascular system, as observed with ageing and lifestyle related diseases, drastically shortens the healthy lifespan with great impact on quality of life. Key components of the cardiovascular system are the heart, the larger conduit arteries, the smaller resistance arteries and the capillaries. The heart ensures a perfusion pressure sufficient to drive oxygenated blood to all regions of the body and especially the elastic and contractile properties of the heart are central elements of optimal cardiac function. The larger arteries serve as highways for blood delivery but importantly also as a pressure reservoir that lessens the workload of the heart. Thus, elasticity of the arterial wall is of outmost importance in absorbing the bulk of blood ejected from the left ventricle during systole and in gently propagating this pressurized blood down the arterial tree. The smaller arteries govern to which regions blood is being delivered and holds a key role in maintaining blood pressure within the optimal range. This function is mediated by a thick layer of smooth muscle cells arranged circumferentially giving the smaller arteries potential to control diameter within a very large range. The smallest vessels of the body, the capillaries are the site of delivery of oxygen and nutrients and removal of waste products. This exchange with the surrounding tissue is secured by the capillary wall structure, only one cell thick and with gaps, slits and transporters, allowing for diffusion and transport of smaller and larger molecules. Functional or structural impairments at any level of this delivery chain from heart to capillary bed affects functionality of the cardiovascular system as they are all reliant on one another. Impairment introduced at one level by ageing or poor lifestyle may lead to conditions like hypertension that affects all levels and in turn can lead to even more severe conditions like heart failure and stroke. Normal ageing has structural and functional impact on the heart and the vasculature that causes cardiovascular function to decrease as we age. These ageing induced changes include decreased elastic and contractile properties of the myocardium and the arterial wall, impaired control of vascular smooth muscle cells and thickening of the delicate capillary structure. Interestingly, lifestyle related diseases, like hypertension and diabetes mellitus, impose similar impairments to all components of the cardiovascular system, even at a very young age. Ultimately, this changes the health trajectory towards earlier morbidity and mortality. Fortunately, detrimental changes to the cardiovascular system can be prevented, stopped or even reversed by physical activity. The focus of this talk will be on cellular mechanisms of ageing and lifestyle related diseases connected to impaired cardiovascular function and how these are affected by physical activity. Classic and novel data from invasive human studies will be presented in order to establish knowledge of how far this field of cardiovascular research has come. Furthermore, the talk will bring focus on future research strings that may have great potential in translating cellular mechanism into lifelong health strategies.