Transcriptomic profiling of human senescent cells upon treatment with the senolytic agent procyanidin C1
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA688509 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13324768_1.fastq.gz | Fastqsanger.gz | |||
| SRR13324768_2.fastq.gz | Fastqsanger.gz | |||
| SRR13324769_1.fastq.gz | Fastqsanger.gz | |||
| SRR13324769_2.fastq.gz | Fastqsanger.gz | |||
| SRR13324770_1.fastq.gz | Fastqsanger.gz |
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Project description:In the course of aging, the long term retention of senescent cells in vivo, a process mainly attributed to highly expressed BCL-family proteins, chronically damages tissues mainly through a senescence-associated secretory phenotype (SASP). It has been documented that accumulation of senescent cells accelerates aging and contributes to age-related diseases. Indeed, senescent cells can be removed by several strategies, thus preventing occurrence of chronic disorders and prolonging lifespan and healthspan. Senolytics, which eliminate senescent cells by pharmacological intervention, have recently emerged as a new line of therapeutic agents to ameliorate diverse age-related pathologies. Achieving the goal using natural or synthetic agents would have a tremendous impact on the quality of life. We report the potential of procyanidin C1 (PCC1), an epicatechin trimer natural product derived from plant sources including grape, apple, and cocoa, in targeting senescent cells via induction of apoptosis. This study demonstrates the efficacy of PCC1 in minimizing the influence of senescent cells in tissue microenvironment and provides a strong rationale for its future use in aging control and geriatric medicine.
2021-10-04 | GSE164012 | GEO
Project description:Physical function declines in advanced age, portending disability, increased health expenditures, and clinical mortality. Cellular senescence leads to tissue dysfunction and contributes to the consequences of aging, but whether age-related pathologies including cancer can be alleviated by targeting senescent cells remains largely unclear. Long term retention of senescent cells in vivo, a process mainly attributed to high expression of BCL2 family proteins, causes chronical tissue damages mainly through the senescence-associated secretory phenotype (SASP). Indeed, senescent cells can be removed by several strategies, thus preventing appearance of chronic symptoms and prolonging healthspan. Strategies involving senolytics, which eliminate senescent cells by pharmacological actions, are recently emerging as a novel and prominent solution to ameliorate diverse age-related pathologies. Achieving the goal using synthetic or natural agents would generate a tremendous impact on the quality of life. We test the potential of procyanidin C1 (PCC1), a B type procyanidin flavonoid derived from plant sources including grape, apple and cocoa, in targeting senescent cells through inducing apoptosis and suppressing the pro-inflammatory phenotype. This study demonstrates the efficacy of PCC1 in restraining the SASP expression and minimizing the influence of senescent stromal cells in tumor microenvironment and provides a strong rationale for its future development in anti-aging industrial pipelines.
2021-10-04 | GSE178376 | GEO
Project description:Transcriptomic profiling of human stromal cells in mouse xenografts upon treatment with chemotherapeutic drug and/or the senolytic agent procyanidin C1
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Project description:Selective removal of senescent cells, or the concept of senolytic therapy, has been proposed to be a potent strategy for overcoming age-related diseases and even reversing aging. We found that nintedanib, a tyrosine kinase inhibitor, selectively induced cell death in primary human diploid fibroblasts undergoing replicative senescence. Similar to ABT263, a well-known senolytic agent, nintedanib triggered intrinsic apoptosis in senescent cells. Additionally, at the concentration producing the senolytic effect, nintedanib arrested the cell cycle of nonsenescent cells in the G1 phase without cytotoxicity. Interestingly, compared with ABT263, nintedanib showed a different mode of activating caspase-9 in the intrinsic apoptotic pathway, in that nintedanib did not suppress the levels of Bcl-2 family proteins in senescent cells. In more detail, nintedanib suppressed the activation of the JAK2/STAT3 pathway, which caused drug-induced cell death in senescent cells. STAT3 knockdown in senescent cells also induced caspase activation. Moreover, nintedanib reduced the number of senescent cells stained based on senescence-associated β-galactosidase activity and airway resistance in a mouse model of bleomycin-induced lung fibrosis. Overall, we identified that nintedanib could be used as a new senolytic agent and that inhibiting STAT3 could be a potential approach for inducing selective cell death in senescent cells. Our findings will pave the way for expanding senolytic toolkits in response to various aging statuses and age-related diseases.
2022-09-06 | GSE210020 | GEO
Project description:Angiosarcoma is an aggressive soft-tissue sarcoma with a poor prognosis. Chemotherapy for this cancer typically employs paclitaxel, one of the taxanes (genotoxic drugs), although it has a limited effect due to chemoresistance for prolonged treatment. Here we examine a new angiosarcoma treatment approach that combines chemotherapeutic and senolytic agents. We first find that the chemotherapeutic drugs, cisplatin and paclitaxel, efficiently induce cellular senescence of angiosarcoma cells. Subsequent treatment with a senolytic agent, ABT-263, eliminates senescent cells through the activation of the apoptotic pathway. In addition, expression analysis indicates that senescence-associated secretory phenotype (SASP) genes are activated in senescent angiosarcoma cells and that ABT-263 treatment eliminates senescent cells expressing genes in the type-I interferon (IFN-I) pathway. Moreover, we show that cisplatin treatment alone requires a high dose to remove angiosarcoma cells, whereas a lower dose of cisplatin is sufficient to induce senescence, followed by the elimination of senescent cells by senolytic treatment. This study sheds light on a potential therapeutic strategy against angiosarcoma by combining a relatively low dose of cisplatin with the ABT-263 senolytic agent, which can help ease the deleterious side effects of chemotherapy.
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Project description:The healthspan of mice is enhanced by selectively killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and burden of age-related chronic diseases. As senescent cells resist apoptosis, we used microarrays to identify transcripts and pathways that differ between senescent and non-senescent preadipocytes, and might be involved in resistance to apoptosis. Primary human abdominal subcutaneous preadipocytes were isolated from 8 healthy lean kidney donors. All subjects were matched by age,gender and BMI. The protocol was approved by the Mayo Clinic Foundation Institutional Review Board for Human Research. Preadipocytes were radiated at 10 Gy to induce senescence or were sham-radiated. From senescent cells RNA was isolated 20 days after irradiation.
2015-03-10 | E-GEOD-66236 | biostudies-arrayexpress
Project description:Ferroptosis as a senolytic target to clear primary and secondary senescent cells
| PRJNA806969 | ENA
Project description:Senescent cells accumulate in organisms over time as a result of tissue damage and impaired immune surveillance and are thought to contribute to age-related tissue decline1,2. In agreement, genetic ablation studies reveal that elimination of senescent cells from aged tissues can ameliorate various age-related pathologies, including metabolic dysfunction and decreased physical fitness3-7. While small-molecule drugs capable of eliminating senescent cells (known as ‘senolytics’) partially replicate these phenotypes, many have uncertain mechanisms of action and all require continuous administration to be effective. As an alternative approach, we previously developed a cell-based senolytic therapy based on chimeric antigen receptor (CAR) T cells targeting uPAR, a cell-surface protein upregulated on senescent cells, and showed these can safely and efficiently eliminate senescent cells in young animals and reverse liver fibrosis8. We now show that uPAR-positive senescent cells accumulate during physiological aging and that they can be safely targeted with senolytic CAR T cells in aged animals. Treatment with anti uPAR CAR T cells ameliorates metabolic dysfunction by improving glucose tolerance and exercise capacity in physiological aging as well as in a model of metabolic syndrome. Importantly, the beneficial effects of senolytic CAR T cells are long lasting; single administration of a low dose is sufficient to achieve long-term therapeutic and preventive effects.
2023-12-08 | GSE243616 | GEO
Project description:The healthspan of mice is enhanced by selectively killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and burden of age-related chronic diseases. As senescent cells resist apoptosis, we used microarrays to identify transcripts and pathways that differ between senescent and non-senescent preadipocytes, and might be involved in resistance to apoptosis.
2015-03-10 | GSE66236 | GEO
Project description:Skeletal muscle mass and function decline with aging, a process known as sarcopenia, and is linked to functional alterations of critical cell types within mature muscle, including fibro-adipogenic progenitors (FAPs) and satellite cells (SCs). Senescence is a form of cellular arrest linked with degenerative diseases of aging, and is thought to be a key driver of aging pathophysiology. We utilized single-cell RNA sequencing to identify novel targets in isolated FAPs and SCs which potentiate senescent cell killing - a process termed senolysis. Using molecular and cellular approaches, we identified the small alpha crystalline heat shock protein CRYAB as a novel senolytic target. We targeted CRYAB using chemical inhibitor screening to identify 25-hydroxycholesterol (25HC), an endogenous metabolite of cholesterol biosynthesis as a potent senolytic capable of killing senescent cells. We validated the potential of 25HC as a senolytic in both mouse and human cells, and in vivo in several tissues including muscle and fat. 25HC treatment therefore represents a potential new class of senolytics, which may be useful in combating diseases or physiologies in which cellular senescence is a key driver.
2022-01-17 | GSE169531 | GEO