Aging and replicative senescence have related effects on human stem and progenitor cells

• Published in: PloS one 2009-06, Vol.4 (6), p.e5846-e5846
• Main Authors: Wagner, Wolfgang, Bork, Simone, Horn, Patrick, Krunic, Damir, Walenda, Thomas, Diehlmann, Anke, Benes, Vladimir, Blake, Jonathon, Huber, Franz-Xaver, Eckstein, Volker, Boukamp, Petra, Ho, Anthony D
• Format: Article
• Language: English
• Subjects: Adult; Age; Age Factors; Aged; Aged, 80 and over; Aging; Aging (artificial); Antigens; Bioinformatics; Blood; Bone marrow; Bone Marrow Cells - cytology; Bone marrow transplantation; Cell Biology/Gene Expression; Cell culture; Cell division; Cell proliferation; Cells (biology); Cellular Senescence; Cord blood; Developmental Biology/Aging; Developmental Biology/Stem Cells; Exhaustion; Female; Gene expression; Gene regulation; Genes; Genomes; Genomics; Hematology; Hematology/Bone Marrow and Stem Cell Transplantation; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Humanities; Humans; Immunophenotyping - methods; Laboratories; Localization; Male; Medicine; Mesenchymal stem cells; Mesenchyme; Middle Aged; Molecular biology; Oligonucleotide Array Sequence Analysis; Peripheral blood; Phenotype; Population; Rodents; Senescence; Skin; Stem cells; Stem Cells - cytology; Stromal cells; Telomerase; Telomeres; Transcription; Transcription (Genetics); Umbilical cord
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0005846

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.