Review Article

Critical Roles of Reactive Oxygen Species in Age-Related Impairment in Ischemia-Induced Neovascularization by Regulating Stem and Progenitor Cell Function

Table 1

Examples of age-dependent exhaustion of EPC numbers and reduction of EPC functions.

StudySubjectsSource of cellsEPC markersEffect of agingReference

Rauscher et al. 20036-month-old versus 1-month-old ApoE−/− miceBMCD31+/CD45−Reduced EPC numbers; progressive development of atherosclerosis[16]
Zhang et al. 200612-month-old versus 3-month-old BALB/C miceBMCD117+/CD34+/Flk1+Decrease in numbers; reduced EPC proliferation, migration, and phagocytic functions[17]
Sugihara et al. 200718-month-old versus 2-month-old C57Bl/6J miceBMAC133+/CD34+ and CD34+/VEGFR2+No difference in numbers of EPCs; impaired VEGF production and EPC migration[18]
Shimada et al. 2004Klotho mutant versus wild type miceBM and peripheral bloodc-kit+/CD31+ and CD34+/CD31+Decrease in EPC numbers postischemia[19]
Chang et al. 200718–24-month-old versus 4–6-month-old C57Bl/6JPeripheral blood and BMCD11b−/Flk1+ and Sca1+/c-kit+/Lin−Decrease in CD11b−/Flk1+ numbers in blood, but not Sca1+/c-kit+/Lin− cells in BM postischemia[11]
68–95-year-old versus 18–35-year-old humanPeripheral bloodAC133+ No difference in EPC numbers at baseline
Zhuo et al. 201015-16-month-old versus 2-month-old ratPeripheral blood and spleenCD34+/KDR+Decreased numbers in response to ischemia, but not at baseline (prior to ischemia)[20]
Shao et al. 201124–26-month-old versus 2-month-old C57Bl/6J miceBMLin−/Sca1+ and Lin−/Sca1+/CXCR4+Decrease in Lin−/Sca1+/CXCR4+, but not Lin−/Sca1+ subpopulation[21]
Boon et al. 201116–18-month-old versus 1-month-old C57Bl/6J micePeripheral bloodLin−/Sca1+/c-kit+, Sca1+/c-kit, and Sca1+/Flk1+Decrease in all 3 populations [22]
Scheubel et al. 2003Patients with CAD; 69 years old versus younger patientsPeripheral bloodAC133+/CD34+Reduced basal circulating EPC levels[23]
Heiss et al. 2005Healthy elderly (average 61 years old) versus healthy young subjects (average 25 years old)Peripheral bloodCD133+/KDR+ and CD34+/KDR+Comparable levels of EPCs[24]

BM, bone marrow.
CAD, coronary artery disease.
mutant mice, an animal model of typical aging, display accelerated arteriosclerosis.