Predictive power of circulating progenitor cell number on longevity in elderly population

Cardiovascular diseases (CVD) and related complications are the main causes of morbidity and mortality in the elderly. Circulating progenitor cells (CPCs), including CD34+ cells, are to date considered a regenerative/reparative potential for CV system, since they are a population of cells in different states of maturation with the ability to differentiate into different cell types, including cardiomyocytes, smooth muscle cells (SMCs), endothelial progenitor cells (EPCs) and endothelial cells (ECs), thus participating in the turnover of healthy and damaged tissues of cardiovascular system, delaying the development of atherosclerosis and CVD. In the present study we observed 100 octogenarians for seven years, in order to address the question of whether CD34+ cell number is a predictor of longevity in selected survivors. We also checked for associations of cell ex-pression of manganese superoxide dismutase (Mn-SOD), catalase (CAT), and glutathione peroxidase type-1 (GPx-1) antioxidative enzymes, and reactive oxigen species (ROS), with number of CD34+ progenitor cells and mortality. We found that in very old subjects the number of CD34+ cells at baseline were higher in subjects who reached older age at death or were still living at the end of observation period (52 subjects, mean plasma concentration 4.09±0.71 cells/mL), with respect to subjects who died from all causes (48 subjects, mean plasma concentration 1.93±1.02 cells/μL, p<0.0001), including CV deaths. We also noted that when MnSOD, CAT and GPx-1 are consistently expressed in the upper tertile, this condition allows reduced production/accumulation of intracellular ROS (on the average 51.2±14.1 FU); on the other hand, when MnSOD, CAT and GPx-1 were expressed in the lower tertile, ROS levels were increased (61.2±16.2, p<0.001). Higher ROS levels were correlated with lower CD34+ cell number; and with lower survival or age reached at the end of observation period. Dependence analysis (Cox regression model) confirmed the central role of CD34+ cell number at the baseline in predicting survival time. Furthermore, HDL-C plasma levels and the classic CV risk factors (hypertension, smoking, hypercholesterolemia), with the exception of diabetes, showed a loss of their predictive power. A significant association between the redox system of CD34+ cells and mortality was also observed. These data suggest that, even in the elderly, CD34+ cells maintain regenerative/reparative potential and consequently their role in predicting mortality, whereas traditional CV risk factors appear to loss their predictive potential, except for diabetes mellitus, that however was associated with lower CD34+ cell number. This study suggest that CD34+ cells could be considered as a biomarker of longevity even in very old subjects.