Vascular Mesenchymal Stromal Cells and Cellular Senescence: A Two-Case Study Investigating the Correlation Between an Inflammatory Microenvironment and Abdominal Aortic Aneurysm Development DOI Open Access
Gabriella Teti,

Riccardo Camiletti,

Valentina Gatta

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12495 - 12495

Published: Nov. 21, 2024

An abdominal aortic aneurysm (AAA) is described as a gradual and localized permanent expansion of the aorta resulting from weakening vascular wall. The key aspects AAA's progression are high proteolysis structural elements wall, depletion smooth muscle cells (VSMCs), chronic immunoinflammatory response. pathological mechanisms underpinning development an AAA complex still unknown. At present, there no successful drug treatments available that can slow or prevent rupture aneurysmal Recently, it has been suggested endothelial cellular senescence may be involved in aging diseases, but clear correlation between AAAs. Therefore, aim this study was to identify presence senescent on wall aneurysmatic aortas correlate their distribution with morphological markers Pathological healthy segments were collected during repair surgery immediately processed for histological immunohistochemical analyses. Hematoxylin/eosin, Verhoeff-van Gieson, Goldner's Masson trichrome staining procedures carried out investigate features related pathology. Immunohistochemical investigations p21

Language: Английский

Subcellular structure, heterogeneity, and plasticity of senescent cells DOI Creative Commons
Thais Cardoso Bitencourt, José Eduardo Vargas,

Andrew Oliveira Silva

et al.

Aging Cell, Journal Year: 2024, Volume and Issue: 23(4)

Published: March 30, 2024

Abstract Cellular senescence is a state of permanent growth arrest. It can be triggered by telomere shortening (replicative senescence) or prematurely induced stresses such as DNA damage, oncogene overactivation, loss tumor suppressor genes, oxidative stress, tissue factors, and others. Advances in techniques experimental designs have provided new evidence about the biology senescent cells (SnCs) their importance human health disease. This review aims to describe main aspects SnCs phenotype focusing on alterations subcellular compartments like plasma membrane, cytoskeleton, organelles, nuclei. We also discuss heterogeneity, dynamics, plasticity SnCs' phenotype, including SASP, pro‐survival mechanisms. advance multiple layers phenotypic heterogeneity SnCs, between inducers, tissues within population discussing relevance these raise challenges well alternatives overcome them. Ultimately, we present open questions perspectives understanding from perspective basic applied questions.

Language: Английский

Citations

16
p53/MDM2 signaling pathway in aging, senescence and tumorigenesis DOI
Youyi Huang, Xiaofang Che, Peter Wang

et al.

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 101, P. 44 - 57

Published: May 17, 2024

Language: Английский

Citations

12
Cellular senescence and PAPP-A DOI
Cheryl A. Conover

Growth Hormone & IGF Research, Journal Year: 2025, Volume and Issue: 80, P. 101637 - 101637

Published: Jan. 23, 2025

Language: Английский

Citations

0
Multiplexed single-cell imaging reveals diverging subpopulations with distinct senescence phenotypes during long-term senescence induction DOI Creative Commons
Garrett A. Sessions,

Madeline V. Loops,

Brian O. Diekman

et al.

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Language: Английский

Citations

0
Transcriptomic signatures and network‐based methods uncover new senescent cell anti‐apoptotic pathways and senolytics DOI Creative Commons

Samael Olascoaga,

Mina Konigsberg,

Jesús Espinal‐Enríquez

et al.

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Cellular senescence is an irreversible cell cycle arrest caused by various stressors that damage cells. Over time, senescent cells accumulate and contribute to the progression of multiple age‐related degenerative diseases. It believed these partly due their ability evade programmed death through development activation survival antiapoptotic resistance mechanisms; however, many aspects how mechanisms develop activate are still unknown. By analyzing transcriptomic signature profiles generated LINCS L1000 project using network‐based methods, we identified genes could represent new senescence‐related mechanisms. Additionally, employing same methodology, over 600 molecules with potential senolytic activity. Experimental validation our computational findings confirmed activity Fluorouracil, whose would be mediated a multitarget mechanism, revealing its targets AURKA, EGFR, IRS1, SMAD4, KRAS pathways (SCAPs). The depend on stimulus induces cellular senescence. SCAP proposed in this work offer insights into survive. Identifying drugs paves way for developing pharmacological therapies eliminate selectively.

Language: Английский

Citations

0
Molecular Signatures of Cellular Senescence in Cancer: A Critical Review of Prognostic Implications and Therapeutic Opportunities DOI

Debora C Santos-Sousa,

Suzan Gonçalves Rosa, Eduardo Cremonese Filippi–Chiela

et al.

Mechanisms of Ageing and Development, Journal Year: 2025, Volume and Issue: unknown, P. 112052 - 112052

Published: March 1, 2025

Language: Английский

Citations

0
BRD4/MAP2K7/PGF Signaling Axis Promotes Senescence and Extracellular Matrix Metabolism of Nucleus Pulposus Cells in Intervertebral Disk Degeneration DOI Creative Commons
Guangzhi Zhang, Lei Li,

Zhili Yang

et al.

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Intervertebral disk degeneration (IDD) is a common age-related degenerative disease of the spine that imposes substantial economic burden on both families and society. Despite advances in understanding mechanisms underlying IDD, effective therapeutic interventions for its treatment prevention remain elusive. Our previous study identified positive correlation between IDD severity bromodomain-containing protein 4 (BRD4) expression. However, multifaceted role BRD4 still not fully understood. This explored abnormal elevation expression nucleus pulposus (NP) tissues from patients with an rat model IDD. We found levels were positively correlated NP senescence extracellular matrix (ECM) degradation inversely ECM anabolism. These relationships further confirmed through assays measuring senescence-associated β-galactosidase activity, markers P21 P16, secretory phenotype indicators (IL-6, IL-8, MMP3, MMP13), as well metabolism such collagen II aggrecan. Mechanistically, aberrant was to upregulate MAP2K7, which turn enhances PGF expression, promoting cell metabolism. findings highlight crucial BRD4/MAP2K7/PGF signaling axis cellular regulation, suggesting represents promising target

Language: Английский

Citations

0
Analysis of the senescence secretome during zebrafish retina regeneration DOI Creative Commons
Gregory Konar, Kyle T. Vallone,

Tu Dac Nguyen

et al.

Frontiers in Aging, Journal Year: 2025, Volume and Issue: 6

Published: April 16, 2025

Zebrafish possess the innate ability to regenerate any lost or damaged retinal cell type with Müller glia serving as resident stem cells. Recently, we discovered that this process is aided by a population of damage-induced senescent immune As part Senescence Associated Secretory Phenotype (SASP), cells secrete numerous factors can play role in modulation inflammation and remodeling microenvironment during regeneration. However, identity specific SASP drive initiation progression retina regeneration remains unclear. We mined Atlas publicly available RNAseq datasets identify common, differentially expressed after injury. These included two distinct acute damage regimens, well chronic, genetic models degeneration. identified overlapping between these used knockdown experiments, qRT/PCR immunohistochemical staining test for one (npm1a). an set 31 SASP-related across all data sets paradigms. are upregulated functions span system, autophagic processing, cycle regulation, cellular stress responses. From among these, show depletion Nucleophosmin 1 (npm1a) inhibits decreases detection damage. Our suggest differential expression promotes both chronic The existence provides group novel therapeutic targets studies.

Language: Английский

Citations

0
Single-cell morphology encodes functional subtypes of senescence in aging human dermal fibroblasts DOI Creative Commons
Pratik Kamat, Nicolas C. Macaluso, Yukang Li

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(17)

Published: April 25, 2025

Cellular senescence, a hallmark of aging, reveals context-dependent phenotypes across multiple biological length scales. Despite its mechanistic importance, identifying and characterizing senescence cell populations is challenging. Using primary dermal fibroblasts, we combined single-cell imaging, machine learning, several induced conditions, protein biomarkers to define functional subtypes. Single-cell morphology analysis revealed 11 distinct clusters. Among these, identified three as bona fide subtypes (C7, C10, C11), with C10 exhibiting the strongest age dependence within an aging cohort. In addition, observed that donor’s burden subtype composition were indicative susceptibility doxorubicin-induced senescence. Functional subtype-dependent responses senotherapies, C7 being most responsive combination dasatinib quercetin. Our framework, SenSCOUT, enables robust identification classification subtypes, offering applications in next-generation senotherapy screens, potential toward explaining heterogeneous based on presence

Language: Английский

Citations

0
Exosomes Released from Senescent Cells and Circulatory Exosomes Isolated from Human Plasma Reveal Aging-associated Proteomic and Lipid Signatures DOI Open Access
Sandip Kumar Patel, Joanna Bons, Jacob Rose

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 25, 2024

Abstract Senescence emerged as a significant mechanism of aging and age-related diseases, offering an attractive target for clinical interventions. Senescent cells release senescence-associated secretory phenotype (SASP), including exosomes that may act signal transducers between distal tissues, propagating secondary or bystander senescence signaling throughout the body. However, composition exosome SASP remains underexplored, presenting opportunity novel unbiased discovery. Here, we present detailed proteomic lipidomic analysis using mass spectrometry from human plasma young older individuals tissue culture senescent primary lung fibroblasts. We identified ~1,300 proteins released by fibroblasts induced three different inducers causing most to be differentially regulated with senescence. In parallel, cohort old revealed over 1,350 171 were when comparing vs individuals. Of age-regulated proteins, observed 52 factors also in fibroblasts, serine protease inhibitors (SERPINs), Prothrombin, Coagulation factor V, Plasminogen, Reelin. addition, 247 lipids high confidence all samples. Following inducers, majority phosphatidylcholine, phosphatidylethanolamine, sphingomyelin species increased significantly indicating cellular membrane changes. The notable categories changed related extracellular matrix remodeling inflammation, both potentially detrimental pathways can damage surrounding tissues even induce Our findings reveal mechanistic insights potential biomarkers, enabling better approach surveilling burden population promising therapeutic targets

Language: Английский

Citations

2