Chemical Screen Identifies a Geroprotective Role of Quercetin in Premature and Physiological Aging
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PROVIDER: PRJNA477529 | ENA |
REPOSITORIES: ENA
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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
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
Project description:Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging
| PRJNA752087 | ENA
Project description:Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging [RNA-seq]
| PRJNA733455 | ENA
Project description:Large-scale Chemical Screen Identifies a Geroprotective Role of Gallic Acid in Premature Aging [ATAC-seq]
| PRJNA752088 | ENA
Project description:Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature aging disease1-5, characterized by premature atherosclerosis and degeneration of vascular smooth muscle cells (SMCs)6-8. HGPS is caused by a single-point mutation in the LMNA gene, resulting in the generation of progerin, a truncated mutant of lamin A. Accumulation of progerin leads to various aging-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin9-12. Here, we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature aging. Upon differentiation of HGPS-iPSCs, progerin and its associated aging consequences are restored. In particular, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescent SMC phenotypes associated with vascular aging. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs) as a component of the progerin-containing protein complex. The absence of nuclear DNAPKcs correlates with premature as well as physiological aging. Since progerin also accumulates during physiological aging6,12,13, our results provide an in vitro iPSC-based model with an acceleration progerin accumulation to study the pathogenesis of human premature and physiological vascular aging. Microarray gene expression profiling was done to: (1) Compare differences between WT fibroblasts and fibroblasts from patients suffering of the Hutchinson-Gilford progeria syndrome (2) Check that iPSC originating from WT and patients are in fact similar to ESC
2011-03-14 | E-GEOD-24487 | biostudies-arrayexpress
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
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
Project description:Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature aging disease1-5, characterized by premature atherosclerosis and degeneration of vascular smooth muscle cells (SMCs)6-8. HGPS is caused by a single-point mutation in the LMNA gene, resulting in the generation of progerin, a truncated mutant of lamin A. Accumulation of progerin leads to various aging-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin9-12. Here, we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature aging. Upon differentiation of HGPS-iPSCs, progerin and its associated aging consequences are restored. In particular, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescent SMC phenotypes associated with vascular aging. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs) as a component of the progerin-containing protein complex. The absence of nuclear DNAPKcs correlates with premature as well as physiological aging. Since progerin also accumulates during physiological aging6,12,13, our results provide an in vitro iPSC-based model with an acceleration progerin accumulation to study the pathogenesis of human premature and physiological vascular aging.
2011-03-14 | GSE24487 | GEO
Project description:Adult stem cells undergo functional degeneration during aging. Quercetin exhibits many beneficial effects against aging and aging-related diseases. Using Drosophila as a model, we explore the efficacy of quercetin against adult stem cell aging and provide effective and feasible therapeutic solutions for preventing the aging-related functional decline of stem cells.
2022-12-06 | GSE216546 | GEO