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Aging and Replicative Senescence Have Related Effects on Human Stem and Progenitor Cells

2009· article· en· 479 citations· W2129298171 on OpenAlex· 10.1371/journal.pone.0005846

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Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

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Opus teacher head0.042
GPT teacher head0.270
Teacher spread
0.228 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

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.

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The record

Venue
PLoS ONE
Topic
Telomeres, Telomerase, and Senescence
Field
Medicine
Canadian institutions
Funders
Deutsche KrebshilfeBundesministerium für Bildung und ForschungDeutsche ForschungsgemeinschaftStem Cell NetworkDeutsches Krebsforschungszentrum
Keywords
TelomereSenescenceBiologyStem cellStem cell theory of agingProgenitor cellMesenchymal stem cellHaematopoiesisTelomeraseDNA methylationSomatic cellCell biologyGene expressionPhenotypeGeneGeneticsStem cell factor
Has abstract in OpenAlex
yes