ETS1 acts as a regulator of human healthy aging via decreasing ribosomal activity

Xiao, Fu-Hui; Yu, Qin; Deng, Zhili; Yang, Ke; Ye, Yunshuang; Ge, Ming-Xia; Yan, Dongjing; Wang, Hao-Tian; Chen, Xiao-Qiong; Yang, Libin; Yang, Bin-Yu; Lin, Rong; Zhang, Wen; Yang, Xiaoxi; Dong, Lei; He, Yonghan; Zhou, Jumin; Cai, Wei; Li, Ji; Kong, Qing‐Peng

doi:10.1126/sciadv.abf2017

Cited by 35 publications

(28 citation statements)

References 38 publications

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“…Our other hit, LIN-1 belongs to the eukaryotic ETS-domain TF family. Recently, expression data from long-lived people observed lower levels of ETS1 TF (Xiao et al, 2022). Our result validates the use of scRNA-seq to find new TFs that influence longevity and suggests an examination of TFs whose expression changes globally with age in other organisms.…”

Section: Discussionmentioning

confidence: 99%

The complete cell atlas of an aging multicellular organism

Roux

Yuan

Podshivalova

et al. 2022

Preprint

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Here we describe a single-cell atlas of aging for the nematode Caenorhabditis elegans. This unique resource describes the expression across adulthood of over 20,000 genes among 211 groups of cells that correspond to virtually every cell type in this organism. Our findings suggest that C. elegans aging is not random and stochastic in nature, but rather characterized by coordinated changes in functionally related metabolic and stress-response genes in a highly cell-type specific fashion. Aging signatures of different cell types are largely different from one another, downregulation of energy metabolism being the only nearly universal change. Some biological pathways, such as genes associated with translation, DNA repair and the ER unfolded protein response, exhibited strong (in some cases opposite) changes in subsets of cell types, but many more were limited to a single cell type. Similarly, the rates at which cells aged, measured as genome-wide expression changes, differed between cell types; some of these differences were tested and validated in vivo by measuring age-dependent changes in mitochondrial morphology. In some, but not all, cell types, aging was characterized by an increase in cell-to-cell variance. Finally, we identified a set of transcription factors whose activities changed coordinately across many cell types with age. This set was strongly enriched for stress-resistance TFs known to influence the rate of aging. We tested other members of this set, and discovered that some, such as GEI-3, likely also regulate the rate of aging. Our dataset can be accessed and queried at c.elegans.aging.atlas.research.calicolabs.com/.

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Section: Discussionmentioning

confidence: 99%

The complete cell atlas of an aging multicellular organism

Roux

Yuan

Podshivalova

et al. 2022

Preprint

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“…For example, ETS proto-oncogene 1 (ETS1) is one of the critical regulators in human aging ( 39 ). We found ETS1 was upregulated in immune cells in aged skin ( Supplementary Figure S1A ).…”

Section: Methodsmentioning

confidence: 99%

AgeAnno: a knowledgebase of single-cell annotation of aging in human

Huang

Gong

Zhang

et al. 2022

Nucleic Acids Research

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Aging is a complex process that accompanied by molecular and cellular alterations. The identification of tissue-/cell type-specific biomarkers of aging and elucidation of the detailed biological mechanisms of aging-related genes at the single-cell level can help to understand the heterogeneous aging process and design targeted anti-aging therapeutics. Here, we built AgeAnno (https://relab.xidian.edu.cn/AgeAnno/#/), a knowledgebase of single cell annotation of aging in human, aiming to provide comprehensive characterizations for aging-related genes across diverse tissue-cell types in human by using single-cell RNA and ATAC sequencing data (scRNA and scATAC). The current version of AgeAnno houses 1 678 610 cells from 28 healthy tissue samples with ages ranging from 0 to 110 years. We collected 5580 aging-related genes from previous resources and performed dynamic functional annotations of the cellular context. For the scRNA data, we performed analyses include differential gene expression, gene variation coefficient, cell communication network, transcription factor (TF) regulatory network, and immune cell proportionc. AgeAnno also provides differential chromatin accessibility analysis, motif/TF enrichment and footprint analysis, and co-accessibility peak analysis for scATAC data. AgeAnno will be a unique resource to systematically characterize aging-related genes across diverse tissue-cell types in human, and it could facilitate antiaging and aging-related disease research.

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“…However, the interference of both HSYA and SYR mainly downregulated the ribosome pathway and upregulated the lysosome pathway in H 2 O 2 -injured cardiomyocytes ( Figures 6K,L ). The significant downregulation of the ribosome pathway in long-lived individuals (LLIs) ( Xiao et al, 2022 ) suggested that downregulating the ribosome pathway can delay cell aging and death. The upregulation of the lysosome function can promote autophagy of damaged cells and then play a role in myocardial protection ( Gu et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Identification of pharmacokinetic markers for safflower injection using a combination of system pharmacology, multicomponent pharmacokinetics, and quantitative proteomics study

et al. 2022

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Safflower injection (SI), a water-extract preparation from safflower (Carthamus tinctorius L.), has been widely used for the treatment of cardio-cerebrovascular diseases. This work aims to develop an approach for identifying PK markers of cardiovascular herbal medicines using SI as a case study. Firstly, qualitative and quantitative analyses were performed to reveal ingredients of the preparation via HPLC-MS. Subsequently, multiple PK ingredients and integrated PK investigations were carried out to ascertain ingredients with favorable PK properties (e.g., easily detected at conventional PK time points and high system exposure) for the whole preparation. Next, ingredients against cardiovascular diseases (CVDs) in the preparation were predicted with target fishing and system pharmacology studies. Finally, ingredients with favorable PK properties, satisfactory PK representativeness for the preparation, and high relevance to CVDs were considered as potential PK markers. Their therapeutic effect was further evaluated using the H2O2-induced H9c2 cardiomyocyte-injured model and a proteomics study to identify objective PK markers. As results, it disclosed that SI mainly contains 11 ingredients. Among them, five ingredients, namely, hydroxysafflor yellow A (HSYA), syringin (SYR), p-coumaric acid (p-CA), scutellarin (SCU), and p-hydroxybenzaldehyde (p-HBA), showed favorable PK properties. HSYA, SYR, and rutin (RU) were predicted to show high relevance to CVDs and screened as potential PK markers. However, only HSYA and SYR were confirmed as therapeutic ingredients against CVDs. Combined with these findings, only HSYA demonstrated satisfactory representativeness on PK properties and therapeutic effects of multiple ingredients of the preparation, thereby indicating that HSYA is a potential PK marker for the SI. The results of this study can provide a reference for the characterization of PK markers for traditional Chinese medicines.

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ETS1 acts as a regulator of human healthy aging via decreasing ribosomal activity

Cited by 35 publications

References 38 publications

The complete cell atlas of an aging multicellular organism

The complete cell atlas of an aging multicellular organism

AgeAnno: a knowledgebase of single-cell annotation of aging in human

Identification of pharmacokinetic markers for safflower injection using a combination of system pharmacology, multicomponent pharmacokinetics, and quantitative proteomics study

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