Aging is associated with a proapoptotic endothelial progenitor cell phenotype
Erich J Kushner1, Owen J MacEneaney, Brian R Weil
1Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA.
Journal of Vascular Research
|June 1, 2011
Summary
Aging increases the susceptibility of endothelial progenitor cells (EPCs) to apoptosis. Older men show reduced antiapoptotic proteins and telomerase activity in EPCs, contributing to impaired function.
Area of Science:
- Gerontology
- Cell Biology
- Cardiovascular Research
Background:
- Endothelial progenitor cells (EPCs) are crucial for vascular repair.
- Aging is associated with impaired vascular function and increased cardiovascular risk.
- The impact of aging on EPC apoptosis sensitivity is not fully understood.
Purpose of the Study:
- To investigate whether aging enhances the sensitivity of EPCs to apoptosis.
- To compare EPC apoptosis in young versus older healthy men.
- To explore age-related changes in key apoptotic and survival proteins within EPCs.
Main Methods:
- Isolation of EPCs from young (25±1 years) and older (61±1 years) healthy men.
- Measurement of intracellular active caspase-3 concentrations following staurosporine stimulation.
- Quantification of protein expression for Akt, p70 S6-kinase, Bcl-2, 14-3-3ε, and Bax.
- Assessment of EPC telomerase activity.
Main Results:
- EPCs from older men exhibited a ~35% higher concentration of active caspase-3 compared to young men (p < 0.05).
- Protein expression of Akt, p70 S6-kinase, and Bcl-2 was significantly lower in older men's EPCs (~35%, ~75%, ~60% respectively, p < 0.05).
- EPC telomerase activity was 57% lower in older men (p < 0.05).
Conclusions:
- Aging is associated with a proapoptotic EPC phenotype.
- Reduced expression of antiapoptotic proteins and decreased telomerase activity contribute to increased EPC apoptosis in older individuals.
- These age-related changes in EPCs may underlie diminished vascular repair capacity and increased cardiovascular risk.
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