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Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE181445 | GEO | 2021/08/05

REPOSITORIES: GEO

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Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging [ATAC-seq]

Project description:Gallic acid (GA) is a natural phenolic compound with antioxidant, anti-inflammatory, and antineoplastic properties. Previous studies also revealed that GA supplementation inhibit the decline of rat embryonic and rejuvenate the immune function in D-gal-induced aging accelerated mice. However, the role of GA in regulating senescence of human premature aging stem cells is unknown. We have demonstrated that GA showed beneficial effects in alleviating human mesenchymal stem cell (hMSC) senescence: (1) GA alleviated senescence by promoting stem cell self-renewal ability and down-regulating the expression of aging markers, including P16 and P21, in Werner syndrome (WS) hMSCs; (2) High levels of reactive oxygen species in total cell as well as mitochondria were both rescued by GA treatment; (3) GA also maintained epigenetic features, enhanced cell stemness, and improved mitochondrial homeostasis in WS hMSCs. Our data provide substantial evidence supporting that GA is a promising candidate agent to

2021-08-05 | GSE181444 | GEO

Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging [RNA-seq]

Project description:Gallic acid (GA) is a natural phenolic compound with antioxidant, anti-inflammatory, and antineoplastic properties. Previous studies also revealed that GA supplementation inhibit the decline of rat embryonic and rejuvenate the immune function in D-gal-induced aging accelerated mice. However, the role of GA in regulating senescence of human premature aging stem cells is unknown. We have demonstrated that GA showed beneficial effects in alleviating human mesenchyme stem cell(hMSC) senescence: (1) GA alleviated senescence by promoting stem cell self-renewal ability and down-regulating the expression of aging markers, including P16 and P21, in Werner syndrome(WS) hMSCs; (2) High levels of reactive oxygen species in total cell as well as mitochondria were both rescued by GA treatment; (3) GA also maintained epigenetic features, enhanced cell stemness, and improved mitochondrial homeostasis in WS hMSCs. Our data provide substantial evidence supporting that GA is a promising candidate agent to

2021-06-25 | GSE175733 | GEO

Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging

Project description:Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging

| PRJNA752087 | ENA

Large-scale chemical screen identifies Gallic acid as a geroprotector for human stem cells.

Project description: Not available

| S-EPMC9226226 | biostudies-literature

Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging [ATAC-seq]

Project description:Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging [ATAC-seq]

| PRJNA752088 | ENA

Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging [RNA-seq]

Project description:Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging [RNA-seq]

| PRJNA733455 | ENA

Chemical screen identifies a geroprotective role of quercetin in premature aging.

Project description:Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.

| S-EPMC6538594 | biostudies-literature

Chemical Screen Identifies a Geroprotective Role of Quercetin in Premature and Physiological Aging

Project description:Aging increases the vulnerability to various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a nature product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate targets were identified and quercetin was further investigated due to its leading effects. Mechanistic studies revealed that in WS hMSCs, quercetin alleviated senescence via the enhancement of cell proliferation and the restoration and differentiation of heterochromatin architecture. RNA-seq analysis uncovered that quercetin and Vitamin C exerted geroprotective effects through different mechanisms. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS), physiological-aging and replicative-senescent hMSCs. More importantly, quercetin significantly improved the exercise endurance of old C57Bl/6 mice. Taken together, our study identifies quercetin as a geroprotective agent against premature and physiological aging, providing a novel therapeutic intervention for treating premature aging and promoting healthy aging.

2018-06-23 | GSE116166 | GEO

Chemical Screen Identifies a Geroprotective Role of Quercetin in Premature and Physiological Aging

Project description:Chemical Screen Identifies a Geroprotective Role of Quercetin in Premature and Physiological Aging

| PRJNA477529 | ENA

A large scale high-throughput screen identifies chemical inhibitors of phosphatidylinositol 4-kinase type II alpha.

Project description:The minor phospholipid, phosphatidylinositol 4-phosphate (PI4P), is emerging as a key regulator of lipid transfer in ER-membrane contact sites. Four different phosphatidylinositol 4-kinase (PI4K) enzymes generate PI4P in different membrane compartments supporting distinct cellular processes, many of which are crucial for the maintenance of cellular integrity but also hijacked by intracellular pathogens. While type III PI4Ks have been targeted by small molecular inhibitors, thus helping decipher their importance in cellular physiology, no inhibitors are available for the type II PI4Ks, which hinders investigations into their cellular functions. Here, we describe the identification of small molecular inhibitors of PI4K type II alpha (PI4K2A) by implementing a large scale small molecule high-throughput screening. A novel assay was developed that allows testing of selected inhibitors against PI4K2A in intact cells using a bioluminescence resonance energy transfer approach adapted to plate readers. The compounds disclosed here will pave the way to the optimization of PI4K2A inhibitors that can be used in cellular and animal studies to better understand the role of this enzyme in both normal and pathological states.

| S-EPMC6399489 | biostudies-literature

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