The clinical research of the Department of Gerontology and Geriatrics of the Leiden University Medical Center focuses on the causes of health and disease in old age. We examine, amongst others, the genetic mechanisms of longevity by comparing children of long-living parents with their partners. At a mean age of 60 years, the children of the long-living parents have a lower prevalence of several cardiometabolic diseases, among which are myocardial infarction, diabetes, and hypertension. The children of the long-living parents also have a more favourable cardiometabolic risk profile, with lower values of glucose, insulin, triglycerides, and thyroid hormone, and a better insulin sensitivity. Moreover, over the past years we have shown that traditional cardiovascular risk factors, such as an increased cholesterol and hypertension, do not automatically apply to the very old. For the very old it must be taken into account that risk profiles for various diseases differ from those of younger populations. The choice of treatment must therefore be based on the 'best available evidence'. In absence of randomized clinical trials this is currently the knowledge on the pathofysiology of health and disease in old age.