• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

从酵母单细胞分析中 pH、生物大分子和细胞器拥挤对衰老的物理化学视角。

A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast.

机构信息

European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.

Department of Cell Biology, Yale School of Medicine, New Haven, United States.

出版信息

Elife. 2020 Sep 29;9:e54707. doi: 10.7554/eLife.54707.

DOI:10.7554/eLife.54707
PMID:32990592
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7556870/
Abstract

Cellular aging is a multifactorial process that is characterized by a decline in homeostatic capacity, best described at the molecular level. Physicochemical properties such as pH and macromolecular crowding are essential to all molecular processes in cells and require maintenance. Whether a drift in physicochemical properties contributes to the overall decline of homeostasis in aging is not known. Here, we show that the cytosol of yeast cells acidifies modestly in early aging and sharply after senescence. Using a macromolecular crowding sensor optimized for long-term FRET measurements, we show that crowding is rather stable and that the stability of crowding is a stronger predictor for lifespan than the absolute crowding levels. Additionally, in aged cells, we observe drastic changes in organellar volume, leading to crowding on the micrometer scale, which we term organellar crowding. Our measurements provide an initial framework of physicochemical parameters of replicatively aged yeast cells.

摘要

细胞衰老（cellular aging）是一个多因素过程，其特征是维持体内平衡的能力下降，在分子水平上表现得最为明显。理化性质（如 pH 值和生物大分子拥挤）对细胞内的所有分子过程都是至关重要的，需要维持其稳定。理化性质的漂移是否会导致衰老过程中整体体内平衡的下降尚不清楚。在这里，我们发现酵母细胞的细胞质在早期衰老时会适度酸化，在衰老后会急剧酸化。使用优化用于长期 FRET 测量的生物大分子拥挤传感器，我们发现拥挤状态相当稳定，拥挤状态的稳定性比绝对拥挤水平更能预测寿命。此外，在衰老的细胞中，我们观察到细胞器体积的剧烈变化，导致在微米尺度上拥挤，我们称之为细胞器拥挤。我们的测量结果为复制性衰老酵母细胞的理化参数提供了一个初步框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/df4ce4904b47/elife-54707-fig4-figsupp4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/e56dce20ce06/elife-54707-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/ff42b5ba6ce0/elife-54707-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/fe5873c483ef/elife-54707-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/d9a41513bb6a/elife-54707-fig1-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/7b372187448c/elife-54707-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/9c1bfb985583/elife-54707-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/acd5acafe0b7/elife-54707-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/c2ae555c57c7/elife-54707-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/1cf6dd3af10b/elife-54707-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/552a7afa5672/elife-54707-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/c1639a692f6c/elife-54707-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/52636131162e/elife-54707-fig4-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/df4ce4904b47/elife-54707-fig4-figsupp4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/e56dce20ce06/elife-54707-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/ff42b5ba6ce0/elife-54707-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/fe5873c483ef/elife-54707-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/d9a41513bb6a/elife-54707-fig1-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/7b372187448c/elife-54707-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/9c1bfb985583/elife-54707-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/acd5acafe0b7/elife-54707-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/c2ae555c57c7/elife-54707-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/1cf6dd3af10b/elife-54707-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/552a7afa5672/elife-54707-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/c1639a692f6c/elife-54707-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/52636131162e/elife-54707-fig4-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3488/7556870/df4ce4904b47/elife-54707-fig4-figsupp4.jpg

相似文献

1
A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast.从酵母单细胞分析中 pH、生物大分子和细胞器拥挤对衰老的物理化学视角。
Elife. 2020 Sep 29;9:e54707. doi: 10.7554/eLife.54707.
2
A physicochemical perspective on cellular ageing.细胞衰老的物理化学视角。
Trends Biochem Sci. 2023 Nov;48(11):949-962. doi: 10.1016/j.tibs.2023.08.007. Epub 2023 Sep 14.
3
Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012).大分子拥挤现象：化学与物理邂逅生物学（瑞士阿斯科纳，2012年6月10日至14日）
Phys Biol. 2013 Aug;10(4):040301. doi: 10.1088/1478-3975/10/4/040301. Epub 2013 Aug 2.
4
Investigating molecular crowding during cell division and hyperosmotic stress in budding yeast with FRET.利用荧光共振能量转移研究出芽酵母细胞分裂和高渗胁迫过程中的分子拥挤现象。
Curr Top Membr. 2021;88:75-118. doi: 10.1016/bs.ctm.2021.09.001. Epub 2021 Nov 16.
5
Estimating network changes from lifespan measurements using a parsimonious gene network model of cellular aging.使用细胞衰老的简约基因网络模型从寿命测量中估计网络变化。
BMC Bioinformatics. 2019 Nov 20;20(1):599. doi: 10.1186/s12859-019-3177-7.
6
Excluded-volume effects in living cells.活细胞中的排除体积效应。
Angew Chem Int Ed Engl. 2015 Feb 16;54(8):2548-51. doi: 10.1002/anie.201409847. Epub 2014 Dec 29.
7
Molecular crowding in single eukaryotic cells: Using cell environment biosensing and single-molecule optical microscopy to probe dependence on extracellular ionic strength, local glucose conditions, and sensor copy number.单细胞中的分子拥挤：利用细胞环境生物传感和单分子光学显微镜来探测对外界离子强度、局部葡萄糖条件和传感器拷贝数的依赖性。
Methods. 2021 Sep;193:54-61. doi: 10.1016/j.ymeth.2020.10.015. Epub 2020 Nov 4.
8
An improved macromolecular crowding sensor CRONOS for detection of crowding changes in membrane-less organelles under stressed conditions.一种改进的大分子拥挤传感器CRONOS，用于检测应激条件下无膜细胞器中的拥挤变化。
Biochem Biophys Res Commun. 2021 Oct 27;583:29-34. doi: 10.1016/j.bbrc.2021.10.055.
9
A functional unfolded protein response is required for chronological aging in Saccharomyces cerevisiae.在酿酒酵母中，功能性未折叠蛋白反应是程序性衰老所必需的。
Curr Genet. 2020 Feb;66(1):263-277. doi: 10.1007/s00294-019-01019-0. Epub 2019 Jul 25.
10
Decreased antioxidant defense during replicative aging of the yeast Saccharomyces cerevisiae studied using the 'baby machine' method.利用“幼芽机器”方法研究酿酒酵母复制性衰老过程中抗氧化防御能力的下降。
FEBS Lett. 2001 Mar 9;492(1-2):123-6. doi: 10.1016/s0014-5793(01)02244-x.

引用本文的文献

1
Liposome-Encapsulated Lysates to Reconstitute Intracellular Macromolecular Crowding Effects.脂质体包裹的裂解物用于重建细胞内大分子拥挤效应。
ACS Synth Biol. 2025 Mar 21;14(3):901-908. doi: 10.1021/acssynbio.4c00824. Epub 2025 Feb 20.
2
A mortality timer based on nucleolar size triggers nucleolar integrity loss and catastrophic genomic instability.基于核仁大小的死亡率计时器会引发核仁完整性丧失和灾难性的基因组不稳定。
Nat Aging. 2024 Dec;4(12):1782-1793. doi: 10.1038/s43587-024-00754-5. Epub 2024 Nov 25.
3
Molecular Spies in Action: Genetically Encoded Fluorescent Biosensors Light up Cellular Signals.

本文引用的文献

1
Transient intracellular acidification regulates the core transcriptional heat shock response.瞬时细胞内酸化调节核心转录热休克反应。
Elife. 2020 Aug 7;9:e54880. doi: 10.7554/eLife.54880.
2
Independent regulation of age associated fat accumulation and longevity.独立调节与年龄相关的脂肪积累和长寿。
Nat Commun. 2020 Jun 3;11(1):2790. doi: 10.1038/s41467-020-16358-7.
3
Loss of vacuolar acidity results in iron-sulfur cluster defects and divergent homeostatic responses during aging in Saccharomyces cerevisiae.液泡酸度的丧失导致酿酒酵母衰老过程中铁硫簇缺陷和不同的稳态反应。
分子间谍大显身手：基因编码荧光生物传感器点亮细胞信号。
Chem Rev. 2024 Nov 27;124(22):12573-12660. doi: 10.1021/acs.chemrev.4c00293. Epub 2024 Nov 13.
4
Macromolecular Crowding, Phase Separation, and Homeostasis in the Orchestration of Bacterial Cellular Functions.大分子拥挤、相分离和内稳态在细菌细胞功能的协调中的作用。
Chem Rev. 2024 Feb 28;124(4):1899-1949. doi: 10.1021/acs.chemrev.3c00622. Epub 2024 Feb 8.
5
Probing macromolecular crowding at the lipid membrane interface with genetically-encoded sensors.利用基因编码传感器探测脂质膜界面的大分子拥挤。
Protein Sci. 2023 Nov;32(11):e4797. doi: 10.1002/pro.4797.
6
Global quantitative understanding of non-equilibrium cell fate decision-making in response to pheromone.对信息素响应中非平衡细胞命运决定的全球定量理解。
iScience. 2023 Sep 9;26(10):107885. doi: 10.1016/j.isci.2023.107885. eCollection 2023 Oct 20.
7
A survey of the specificity and mechanism of 1,6 hexanediol-induced disruption of nuclear transport.1,6-己二醇诱导的核转运破坏的特异性和机制研究综述。
Nucleus. 2023 Dec;14(1):2240139. doi: 10.1080/19491034.2023.2240139.
8
Cell wall damage increases macromolecular crowding effects in the cytoplasm.细胞壁损伤会增加细胞质中的大分子拥挤效应。
iScience. 2023 Mar 9;26(4):106367. doi: 10.1016/j.isci.2023.106367. eCollection 2023 Apr 21.
9
Correlating viscosity and molecular crowding with fluorescent nanobeads and molecular probes: and .用荧光纳米珠和分子探针关联粘度与分子拥挤现象：以及。 （注：原文最后“and.”表述不太完整准确，翻译出来可能会有些奇怪，但严格按照要求进行了翻译）
Interface Focus. 2022 Oct 14;12(6):20220042. doi: 10.1098/rsfs.2022.0042. eCollection 2022 Dec 6.
10
A Microfluidic Platform for Tracking Individual Cell Dynamics during an Unperturbed Nutrients Exhaustion.一种用于在未受干扰的营养物质耗尽过程中追踪单个细胞动态的微流控平台。
Bio Protoc. 2022 Jul 20;12(14). doi: 10.21769/BioProtoc.4470.
Geroscience. 2020 Apr;42(2):749-764. doi: 10.1007/s11357-020-00159-3. Epub 2020 Jan 23.
4
DNA damage checkpoint activation impairs chromatin homeostasis and promotes mitotic catastrophe during aging.DNA 损伤检查点的激活会破坏染色质的动态平衡，并在衰老过程中促进有丝分裂灾难。
Elife. 2019 Nov 12;8:e50778. doi: 10.7554/eLife.50778.
5
Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence.细胞过度生长导致细胞质稀释，并导致衰老。
Cell. 2019 Feb 21;176(5):1083-1097.e18. doi: 10.1016/j.cell.2019.01.018. Epub 2019 Feb 7.
6
Influence of Fluorescent Protein Maturation on FRET Measurements in Living Cells.荧光蛋白成熟度对活细胞中 FRET 测量的影响。
ACS Sens. 2018 Sep 28;3(9):1735-1742. doi: 10.1021/acssensors.8b00473. Epub 2018 Sep 12.
7
mTORC1 Controls Phase Separation and the Biophysical Properties of the Cytoplasm by Tuning Crowding.mTORC1 通过调节拥挤程度来控制相分离和细胞质的物理性质。
Cell. 2018 Jul 12;174(2):338-349.e20. doi: 10.1016/j.cell.2018.05.042. Epub 2018 Jun 21.
8
Distributed and dynamic intracellular organization of extracellular information.细胞外信息的分布式和动态细胞内组织。
Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):6088-6093. doi: 10.1073/pnas.1716659115. Epub 2018 May 21.
9
The oxidation state of the cytoplasmic glutathione redox system does not correlate with replicative lifespan in yeast.细胞质谷胱甘肽氧化还原系统的氧化状态与酵母的复制寿命不相关。
NPJ Aging Mech Dis. 2016 Dec 15;2:16028. doi: 10.1038/npjamd.2016.28. eCollection 2016.
10
The Centrosome Is a Selective Condensate that Nucleates Microtubules by Concentrating Tubulin.中心体是一种选择性凝聚物，通过浓缩微管蛋白来成核微管。
Cell. 2017 Jun 1;169(6):1066-1077.e10. doi: 10.1016/j.cell.2017.05.028.