More and more people are living into the 90s or becoming centenarians. But, the gift of increased 'age span' seldom equates with an improved 'health-span'. Governments across the world are expressing concern about the epidemic of chronic disease, and have responded by initiating policies that make prevention, reduction and treatment of chronic disease, a public health priority. But understanding, how to age long and well, with the avoidance of chronic disease and later life complex disease morbidity is challenging. While inherited genes have an undoubted role to play in the chance of maintaining good health or conversely a predilection to developing disease and chronic ill health, there is increasing evidence that behavioural and environmental life-style choices may contribute up to 50% of the variability of human lifespan. Physical exercise is readily available to everyone, and is a simple cheap and effective form of life-style intervention. Exercise appears to help maintain good health and to reduce the risk of developing chronic disease and ill health. Evidence suggests that physical activity improves well-being across many health domains through out life, continues to offer important health benefits in older age groups and tracks with a 'healthy ageing' profile. Although many of the molecular pathways remain to be fully identified, here we discuss how physical activity and exercise is understood to produce changes in the human epigenome, which have the potential to enhance cognitive and psychological health, improve muscular fitness, and lead to better ageing with improved quality of life in older age.