The rate of ageing in humans is not uniform, due to genetic heterogeneity and the influence of environmental factors. Age-related changes in body function or composition that could serve as a measure of biological age and predict the onset of age-related diseases and/or residual lifetime are termed biomarkers of ageing . Many candidate biomarkers have been proposed but in all cases their variability in cross-sectional studies is considerable, and therefore no single measurement has so far proven to yield a useful biomarker of ageing on its own, probably due to the multi-causal and multi-system nature of ageing. We propose to conduct a population study (3,700 probands) to identify a set biomarkers of ageing which, as a combination of parameters with appropriate weighting, would measure biological age better than any marker in isolation. Two large groups of subjects will be recruited, i.e. (1) randomly recruited age-stratified individuals from the general population covering the age range 35-74 years and (2) subjects born from a long-living parent belonging to a family with long living sibling(s) already recruited in the framework of the GEHA project. For genetic reasons such individuals ( GEHA offspring ) are expected to age at a slower rate. They will be recruited together with their spouses as controls, thus allowing initial validation of the biomarkers identified. (3) A small number of patients with progeroid syndromes will also be included in the study. A wide range of candidate biomarkers will be tested, including (a) classical ones for which data from several smaller studies have been published; (b) new ones, based on recent preliminary data, as well as © novel ones, based on recent research on mechanistic aspects of ageing, conducted by project participants. Bioinformatics will be used in order to extract a robust set of biomarkers of human ageing from the large amounts of data to be generated and to derive a model for healthy ageing.