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衰老细胞溶解化合物可在体外降低血液样本的表观遗传年龄。

Senolytic compounds reduce epigenetic age of blood samples in vitro.

作者信息

Tharmapalan Vithurithra, Du Marchie Sarvaas Miriam, Bleichert Michael, Wessiepe Martina, Wagner Wolfgang

机构信息

Institute for Stem Cell Biology, RWTH Aachen University Medical School, 52074, Aachen, Germany.

Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical Faculty, 52074, Aachen, Germany.

出版信息

NPJ Aging. 2025 Feb 4;11(1):6. doi: 10.1038/s41514-025-00199-z.

DOI:10.1038/s41514-025-00199-z
PMID:39905063
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11794651/
Abstract

Senolytic drugs raise the expectation that they can specifically eliminate a subset of senescent cells in a given tissue. In this study, we have exemplarily analyzed if a 3-day treatment of human blood samples in vitro would reduce age-associated biomarkers, with a particular focus on epigenetic age-predictions. Of eight tested compounds, JQ1, RG7112, nutlin-3a, and AMG232 reduced epigenetic age, indicating that this approach may be useful in drug screening for senolytic compounds.

摘要

衰老细胞裂解药物让人期待它们能够特异性地清除特定组织中的衰老细胞亚群。在本研究中,我们已进行了示例性分析,即体外对人类血液样本进行为期3天的处理是否会降低与年龄相关的生物标志物,特别关注表观遗传年龄预测。在八种测试化合物中,JQ1、RG7112、nutlin-3a和AMG232降低了表观遗传年龄,表明这种方法可能有助于衰老细胞裂解化合物的药物筛选。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2c2/11794651/c5aac78782bf/41514_2025_199_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2c2/11794651/ab3e0b7d91bd/41514_2025_199_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2c2/11794651/c5aac78782bf/41514_2025_199_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2c2/11794651/ab3e0b7d91bd/41514_2025_199_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2c2/11794651/c5aac78782bf/41514_2025_199_Fig2_HTML.jpg

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本文引用的文献

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Genes Dev. 2024 Oct 16;38(17-20):823-842. doi: 10.1101/gad.351728.124.
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A Fully-Automated Senescence Test (FAST) for the high-throughput quantification of senescence-associated markers.一种用于高通量定量衰老相关标志物的全自动衰老测试(FAST)。
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Aging clocks based on accumulating stochastic variation.基于累积随机变化的衰老时钟。
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Nature of epigenetic aging from a single-cell perspective.从单细胞角度看表观遗传衰老的本质。
Nat Aging. 2024 Jun;4(6):854-870. doi: 10.1038/s43587-024-00616-0. Epub 2024 May 9.
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Quantifying the stochastic component of epigenetic aging.量化表观遗传衰老的随机成分。
Nat Aging. 2024 Jun;4(6):886-901. doi: 10.1038/s43587-024-00600-8. Epub 2024 May 9.
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Clinical validation of CFDG as a marker associated with senescence and osteoarthritic phenotypes.临床验证 CFDA 作为与衰老和骨关节炎表型相关的标志物。
Aging Cell. 2024 May;23(5):e14113. doi: 10.1111/acel.14113. Epub 2024 May 6.
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