ArticleEMBO reports2020
Small-molecule inhibition of aging-associated chromosomal instability delays cellular senescence.
Article in EMBO reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 52 citations in OpenAlex.
- Mechanical constraints regulate embryonic stem cell mitosis in the developing brain.The EMBO journal · 2026Article
- A tumour-host feed-forward loop contributes to the growth of chromosomal instability-induced tumours.EMBO reports · 2026Article
- Human fibroblasts from aged individuals exhibit chromosomal instability through replication stress caused by oxidative stress.npj aging · 2025Article
- Article
- Cancer and Aging Biomarkers: Classification, Early Detection Technologies and Emerging Research Trends.Biosensors · 2025Review
- Chromosome mis-segregation triggers cell cycle arrest through a mechanosensitive nuclear envelope checkpoint.Nature cell biology · 2025Article
- Remodeling of cytoskeleton, chromatin, and gene expression during mechanical rejuvenation of aged human dermal fibroblasts.Molecular biology of the cell · 2025Article
- Measuring and modeling the dynamics of mitotic error correction.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Replication stress as a driver of cellular senescence and aging.Communications biology · 2024Review
- Chromosomal instability as an architect of the cancer stemness landscape.Frontiers in cell and developmental biology · 2024Review
- Compromised Mitotic Fidelity in Human Pluripotent Stem Cells.International journal of molecular sciences · 2023Review
- A pluripotent developmental state confers a low fidelity of chromosome segregation.Stem cell reports · 2023Article
- The Molecular Mechanism of Polyphenols with Anti-Aging Activity in Aged Human Dermal Fibroblasts.Molecules (Basel, Switzerland) · 2022Review
- Effects of aneuploidy on cell behaviour and function.Nature reviews. Molecular cell biology · 2022Review
- Review
- Molecular mechanisms and cardiovascular implications of cancer therapy-induced senescence.Pharmacology & therapeutics · 2021Review
- Aneuploidy as a promoter and suppressor of malignant growth.Nature reviews. Cancer · 2021Review
- Review
- Towards restoring proper chromosome segregation and preventing ageing.EMBO reports · 2020Article
- Small-molecule inhibition of aging-associated chromosomal instability delays cellular senescence.EMBO reports · 2020Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Chromosomal instability (CIN) refers to the rate at which cells are unable to properly segregate whole chromosomes, leading to aneuploidy. Besides its prevalence in cancer cells and postulated implications in promoting tumorigenesis, studies in aneuploidy-prone mouse models uncovered an unanticipated link between CIN and aging. Using young to old-aged human dermal fibroblasts, we observed a dysfunction of the mitotic machinery arising with age that mildly perturbs chromosome segregation fidelity and contributes to the generation of fully senescent cells. Here, we investigated mitotic mechanisms that contribute to age-associated CIN. We found that elderly cells have an increased number of stable kinetochore-microtubule (k-MT) attachments and decreased efficiency in the correction of improper k-MT interactions. Chromosome mis-segregation rates in old-aged cells decreased upon both genetic and small-molecule enhancement of MT-depolymerizing kinesin-13 activity. Notably, restored chromosome segregation accuracy inhibited the phenotypes of cellular senescence. Therefore, we provide mechanistic insight into age-associated CIN and disclose a strategy for the use of a small-molecule to inhibit age-associated CIN and to delay the cellular hallmarks of aging.
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Registered trials
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.