ArticlePloS one2011
Accumulation of DNA damage in hematopoietic stem and progenitor cells during human aging.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
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Who cites it
160 citing papers in PubMed, 295 citations in OpenAlex.
- Association of mitochondrial DNA haplogroup, oxidative DNA damage and inflammatory markers in middle-aged adults.International journal of radiation biology · 2026Article
- Clonal hematopoiesis of indeterminate potential (CHIP)-a pivotal contributor of aging and related disorders.Annals of translational medicine · 2026Review
- Inflammageing and clonal haematopoiesis interplay and their impact on human disease.Nature reviews. Molecular cell biology · 2026Review
- Aging of the Hematopoietic System: Mechanisms, Consequences, and Systemic Interactions.Aging cell · 2026Review
- Mechanistic redundancy and hierarchy of aging mechanisms: implications for strategies to extend healthspan and biomarker integration.Frontiers in aging · 2026Review
- Haematopoietic ageing in health and lifespan.Nature cell biology · 2025Review
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- The role of genetic/epigenetic factors and microenvironment in hematopoietic stem cell ageing.Biogerontology · 2025Review
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- Unraveling the ROS-Inflammation-Immune Balance: A New Perspective on Aging and Disease.Aging and disease · 2025Review
- Anti-Aging Tests for Middle Aged Women.Journal of menopausal medicine · 2024Review
- DNA fork remodeling proteins, Zranb3 and Smarcal1, are uniquely essential for aging hematopoiesis.Aging cell · 2024Article
- Enhancing genome editing in hPSCs through dual inhibition of DNA damage response and repair pathways.Nature communications · 2024Article
- Age and dose dependent changes to the bone and bone marrow microenvironment after cytotoxic conditioning with busulfan.Frontiers in cell and developmental biology · 2024Article
- Frailty, sex, and poverty are associated with DNA damage and repair in frail, middle-aged urban adults.DNA repair · 2023Article
- Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner.Molecular cell · 2023Article
- Unraveling Heterogeneity in the Aging Hematopoietic Stem Cell Compartment: An Insight From Single-cell Approaches.HemaSphere · 2023Review
- Impact of Age on Poly(ADP-Ribose) Polymerase Inhibitor (PARPi)-Induced Lymphopenia: A Scoping Review of the Literature and Internal Analysis of a Retrospective Database.Drugs & aging · 2023Article
- Biomarkers of aging.Science China. Life sciences · 2023Review
100 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAccumulation of DNA damage leading to adult stem cell exhaustion has been proposed to be a principal mechanism of aging. Here we tested this hypothesis in healthy individuals of different ages by examining unrepaired DNA double-strand breaks (DSBs) in hematopoietic stem/progenitor cells matured in their physiological microenvironment. METHODOLOGY/PRINCIPAL
findingsTo asses DNA damage accumulation and repair capacities, γH2AX-foci were examined before and after exposure to ionizing irradiation. Analyzing CD34+ and CD34- stem/progenitor cells we observed an increase of endogenous γH2AX-foci levels with advancing donor age, associated with an age-related decline in telomere length. Using combined immunofluorescence and telomere-fluorescence in-situ hybridization we show that γH2AX-foci co-localize consistently with other repair factors such as pATM, MDC1 and 53BP1, but not significantly with telomeres, strongly supporting the telomere-independent origin for the majority of foci. The highest inter-individual variations for non-telomeric DNA damage were observed in middle-aged donors, whereas the individual DSB repair capacity appears to determine the extent of DNA damage accrual. However, analyzing different stem/progenitor subpopulations obtained from healthy elderly (>70 years), we observed an only modest increase in DNA damage accrual, most pronounced in the primitive CD34+CD38(-)-enriched subfraction, but sustained DNA repair efficiencies, suggesting that healthy lifestyle may slow down the natural aging process. CONCLUSIONS/SIGNIFICANCE: Based on these findings we conclude that age-related non-telomeric DNA damage accrual accompanies physiological stem cell aging in humans. Moreover, aging may alter the functional capacity of human stem cells to repair DSBs, thereby deteriorating an important genome protection mechanism leading to exceeding DNA damage accumulation. However, the great inter-individual variations in middle-aged individuals suggest that additional cell-intrinsic mechanisms and/or extrinsic factors contribute to the age-associated DNA damage accumulation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.