A5078708669- Telomeres, Telomerase, and Senescence
- RNA Research and Splicing
- RNA modifications and cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Atherosclerosis and Cardiovascular Diseases
- Circular RNAs in diseases
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Single-cell and spatial transcriptomics
- RNA regulation and disease
- Adipokines, Inflammation, and Metabolic Diseases
- Genetics, Aging, and Longevity in Model Organisms
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Adipose Tissue and Metabolism
- Cardiovascular Disease and Adiposity
- Autophagy in Disease and Therapy
- Peptidase Inhibition and Analysis
- RNA Interference and Gene Delivery
- Cytokine Signaling Pathways and Interactions
- Genetics and Neurodevelopmental Disorders
- Endoplasmic Reticulum Stress and Disease
- Advanced biosensing and bioanalysis techniques
- Skin Protection and Aging
- Hippo pathway signaling and YAP/TAZ
National Institute on Aging
2020-2024
National Institutes of Health
2020-2024
University of Michigan–Ann Arbor
2024
Institute on Aging
2020-2023
Institut thématique Génétique, génomique et bioinformatique
2022-2023
Yeungnam University
2022
Park University
2022
Inha University
2022
Korea University
2022
Government of the United States of America
2022
Mammalian circRNAs can influence different cellular processes by interacting with proteins and other nucleic acids. Here, we used ribonucleoprotein immunoprecipitation (RIP) analysis to identify systematically the associated cancer-related protein AUF1. Among AUF1 in HeLa (human cervical carcinoma) cells, focused on hsa_circ_0032434 (circPCNX), an abundant target of Overexpression circPCNX specifically interfered binding p21 (CDKN1A) mRNA, thereby promoting mRNA stability elevating...
Cells responding to DNA damage implement complex adaptive programs that often culminate in one of two distinct outcomes: apoptosis or senescence. To systematically identify factors driving each response, we analyzed human IMR-90 fibroblasts exposed increasing doses the genotoxin etoposide and identified SRC as a key kinase contributing early this dichotomous decision. was activated by low but not high levels etoposide. With damage, SRC-mediated activation p38 critically promoted expression...
Senescent vascular smooth muscle cells (VSMCs) accumulate in the vasculature with age and tissue damage secrete factors that promote atherosclerotic plaque vulnerability disease. Here, we report increased levels activity of dipeptidyl peptidase 4 (DPP4), a serine protease, senescent VSMCs. Analysis conditioned media from VSMCs revealed unique senescence-associated secretory phenotype (SASP) signature comprising many complement coagulation factors; silencing or inhibiting DPP4 reduced these...
Stress granules (SGs) are dynamic cytoplasmic aggregates containing mRNA, RNA-binding proteins, and translation factors that form in response to cellular stress. SGs have been shown contribute the pathogenesis of several human diseases, but their role vascular diseases is unknown. This study shows accumulate smooth muscle cells (VSMCs) macrophages during atherosclerosis. Approach Results: Immunohistochemical analysis atherosclerotic plaques from LDLR-/- mice revealed an increase stress...
Cellular senescence is characterized by cell cycle arrest, resistance to apoptosis, and a senescence-associated secretory phenotype (SASP) whereby cells secrete pro-inflammatory tissue-remodeling factors. Given that the SASP exacerbates age-associated pathologies, some aging interventions aim at selectively eliminating senescent cells. In this study, drug library screen uncovered TrkB (NTRK2) inhibitors capable of triggering apoptosis several senescent, but not proliferating, human Senescent...
Cardiovascular disease (CVD) is the leading cause of mortality and morbidity for all sexes, racial ethnic groups. Age, its associated physiological pathological consequences, exacerbate CVD incidence progression, while modulation biological age with interventions track cardiovascular health. Despite strong link between aging CVD, surprisingly few studies have directly investigated heart failure vascular dysfunction in aged models subjects. Nevertheless, correlations been found disease,...
Aging | doi:10.18632/aging.203170. Rachel Munk, Carlos Anerillas, Martina Rossi, Dimitrios Tsitsipatis, Jennifer L. Martindale, Allison B. Herman, Jen-Hao Yang, Jackson A. Roberts, Vijay R. Varma, Poonam Pandey, Madhav Thambisetty, Myriam Gorospe, Kotb Abdelmohsen
Senescent cells release a variety of cytokines, proteases, and growth factors collectively known as the senescence-associated secretory phenotype (SASP). Sustained SASP contributes to pattern chronic inflammation associated with aging implicated in many age-related diseases. Here, we investigated expression function immunomodulatory cytokine BAFF (B-cell activating factor; encoded by TNFSF13B gene), protein, multiple senescence models. We first characterized production across different...
Abstract Changes in the transcriptomes of human tissues with advancing age are poorly cataloged. Here, we sought to identify coding and long noncoding RNAs present cultured primary skin fibroblasts collected from 82 healthy individuals across a wide spectrum (22–89 years old) who participated GESTALT (Genetic Epigenetic Signatures Translational Aging Laboratory Testing) study National Institute on Aging, NIH. Using high‐throughput RNA sequencing linear regression model, identified 1437...
This work identifies the fragile-X-related protein (FXR1) as a reciprocal regulator of HuR target transcripts in vascular smooth muscle cells (VSMCs). FXR1 was identified an HuR-interacting by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The HuR-FXR1 interaction is abrogated RNase-treated extracts, indicating that their association tethered mRNAs. expression induced diseased but not normal arteries. siRNA knockdown increases abundance and stability inflammatory mRNAs, while...
Abstract Changes in the proteome of different human tissues with advancing age are poorly characterized. Here, we studied proteins present primary skin fibroblasts collected from 82 healthy individuals across a wide spectrum (22–89 years old) who participated GESTALT (Genetic and Epigenetic Signatures Translational Aging Laboratory Testing) study National Institute on Aging, NIH. Proteins were extracted lysed subjected to liquid chromatography‐mass spectrometry analysis, expression levels...
Objective— To test the hypothesis that loss of IL-19 (interleukin-19) exacerbates atherosclerosis. Approach and Results— Il19 −/− mice were crossed into Ldlr (low-density lipoprotein receptor knock out) mice. Double knockout (dKO) had increased plaque burden in aortic arch root compared with controls after 14 weeks high-fat diet (HFD). dKO injected 10 ng/g per day rmIL-19 significantly less controls. qRT-PCR Western blot analysis revealed systemic intraplaque polarization T cells macrophages...
Abstract A major stress response influenced by microRNAs (miRNAs) is senescence, a state of indefinite growth arrest triggered sublethal cell damage. Here, through bioinformatic analysis and experimental validation, we identified miR-340-5p as novel miRNA that foments cellular senescence. was highly abundant in diverse senescence models, overexpression proliferating cells rendered them senescent. Among the target mRNAs, prominently reduced levels LBR mRNA, encoding lamin B receptor (LBR)....
Interleukin enhancer-binding factor 3 (ILF3), an RNA-binding protein, is best known for its role in innate immunity by participation cellular antiviral responses. A ILF3 angiogenesis unreported. expression CD31
Aging | doi:10.18632/aging.204450. Dimitrios Tsitsipatis, Krystyna Mazan-Mamczarz, Ying Si, Allison B. Herman, Jen-Hao Yang, Abhishek Guha, Yulan Piao, Jinshui Fan, Jennifer L. Martindale, Rachel Munk, Xiaoling Supriyo De, Brijesh K. Singh, Ritchie Ho, Myriam Gorospe, Peter H. King
Abstract Extracellular vesicles and particles (EVPs) are secreted by organs across the body into different circulatory systems, including bloodstream, reflect pathophysiologic conditions of organ. However, heterogeneity EVPs in blood makes it challenging to determine their organ origin. We hypothesized that small (s)EVPs (<100 nm diameter) bloodstream carry distinctive protein signatures associated with each originating organ, we investigated this possibility studying proteomes sEVPs...
The iprA gene (formerly known as yaiV or STM0374) is located in a two-gene operon the Salmonella enterica serovar Typhimurium genome and associated with altered expression during spaceflight rotating-wall-vessel culture conditions that increase virulence. However, uncharacterized literature. In this report, we present first targeted characterization of gene, which revealed highly conserved across Enterobacteriaceae We found S Typhimurium, Escherichia coli, Enterobacter cloacae ΔiprA mutant...
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During cellular senescence, persistent growth arrest and changes in protein expression programs are accompanied by a senescence-associated secretory phenotype (SASP). In this study, we detected the upregulation of SASP-related dipeptidyl peptidase 4 (DDP4) human primary lung cells rendered senescent exposure to ionizing radiation. DPP4 is an exopeptidase that plays crucial role cleavage various proteins, resulting loss N-terminal dipeptides proinflammatory effects. Interestingly, our data...