Aging and Replicative Senescence Have Related Effects on Human Stem and Progenitor Cells
Open Access
- 9 June 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (6), e5846
- https://doi.org/10.1371/journal.pone.0005846
Abstract
The regenerative potential diminishes with age and this has been ascribed to functional impairments of adult stem cells. Cells in culture undergo senescence after a certain number of cell divisions whereby the cells enlarge and finally stop proliferation. This observation of replicative senescence has been extrapolated to somatic stem cells in vivo and might reflect the aging process of the whole organism. In this study we have analyzed the effect of aging on gene expression profiles of human mesenchymal stromal cells (MSC) and human hematopoietic progenitor cells (HPC). MSC were isolated from bone marrow of donors between 21 and 92 years old. 67 genes were age-induced and 60 were age-repressed. HPC were isolated from cord blood or from mobilized peripheral blood of donors between 27 and 73 years and 432 genes were age-induced and 495 were age-repressed. The overlap of age-associated differential gene expression in HPC and MSC was moderate. However, it was striking that several age-related gene expression changes in both MSC and HPC were also differentially expressed upon replicative senescence of MSC in vitro. Especially genes involved in genomic integrity and regulation of transcription were age-repressed. Although telomerase activity and telomere length varied in HPC particularly from older donors, an age-dependent decline was not significant arguing against telomere exhaustion as being causal for the aging phenotype. These studies have demonstrated that aging causes gene expression changes in human MSC and HPC that vary between the two different cell types. Changes upon aging of MSC and HPC are related to those of replicative senescence of MSC in vitro and this indicates that our stem and progenitor cells undergo a similar process also in vivo.Keywords
This publication has 75 references indexed in Scilit:
- Hematopoietic stem cell aging and self-renewalCell and tissue research, 2007
- Age-related transcription levels of KU70, MGST1 and BIK in CD34+ hematopoietic stem and progenitor cellsMechanisms of Ageing and Development, 2007
- Mesenchymal Stem Cell Preparations—Comparing Apples and OrangesStem Cell Reviews and Reports, 2007
- Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespanAging Cell, 2007
- Aging Hematopoietic Stem Cells Decline in Function and Exhibit Epigenetic DysregulationPLoS Biology, 2007
- Epigenetic Control of Hematopoietic Stem Cell Aging The Case of Ezh2Annals of the New York Academy of Sciences, 2007
- Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord bloodExperimental Hematology, 2005
- Stem cells and ageingEMBO Reports, 2005
- Cell intrinsic alterations underlie hematopoietic stem cell agingProceedings of the National Academy of Sciences of the United States of America, 2005
- Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statementCytotherapy, 2005