Short Telomere in Patients at High Cardiovascular Risk: a Simple Marker or a Major Determinant of Accelerated Arterial Aging

The prevailing view in telomere(definition) epidemiology is that leukocyte telomere length (LTL) is associated with atherosclerosis and accelerated aging since it serves as a biomarker of the cumulative burden of inflammation and oxidative stress during adult life. Our recent results however, indicate that telomere length (TL) is mainly determined at birth and childhood. Since short telomeres ante cede atherosclerosis, the investigators hypothesize that TL is not just a simple marker, but a real determinant of arterial aging. That is because TL reflects cellular repair capacity and a short LTL denotes diminished repair reserves. This hypothesis cannot be tested by measurements of LTL alone, since this parameter reflects TL at birth and its age-dependent attrition thereafter. The investigators propose, therefore, a model that makes it possible to examine different elements of TL dynamics in different tissues: leukocytes, skeletal muscle, endothelial progenitor cells (EPCs), skin or subcutaneous fat in patients with or without atherosclerosis. Our model is based on the following premises, which are derived from observations that TL is synchronized (equivalent) across somatic tissues/cells of the newborn: * TL in skeletal muscle mainly reflects TL at birth * The difference in TL between muscle and leukocytes in adults (approximately 1.5 Kbp) mainly reflects LTL attrition during the growth period, i.e., childhood/adolescence * TL in EPCs determines the cell proliferative ability and therefore capacity for vessels repair during aging. The general aim of the present project is to examine the links of arterial aging with TL, as expressed in different tissues, and LTL dynamics, as expressed in the difference between TLs of muscle and leukocytes.