Alterations of Liver Morphology in Senescent Rats DOI Open Access
Ruth Maldonado-Rengel, Zaida Sócola-Barsallo, Bélgica Vásquez

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9846 - 9846

Published: Sept. 12, 2024

Age-related liver changes can have important implications for health and metabolic function. This study aimed to describe the morphoquantitative alterations of in senescent rats compared adult rats. Twelve male were used, divided into 6-month-old adults (group A) 36-month-old S). Morphometric histopathological studies, quantification collagen types I III, stereological analyses performed determine volume density mononucleated (VvhepM) binucleated (VvhepB) hepatocyte nuclei, surface area (SvhepM), number (NvhepM) nuclei. The findings reveal an alteration normal tissue architecture presence inflammatory lesions fibrosis. In addition, there was a decrease body mass volume. Group S showed significant reduction VvhepM NvhepM; however, SvhepM significantly higher. No differences noted percentage hepatocytes between two groups. reveals substantial morphological aging liver, with possible functional implications. More research is needed on underlying mechanisms their consequences at older ages.

Language: Английский

Involvement of SIRT1-mediated aging in liver diseases DOI Creative Commons
Yueming Zhang, Chang Gong, Lina Tao

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 20, 2025

Liver disease is a significant global health issue, responsible for millions of deaths annually. Aging, characterized by the gradual decline in cellular and physiological functions, impairs tissue regeneration, increases susceptibility to liver diseases, leads health. Silent information regulator 1 (SIRT1), NAD⁺-dependent deacetylase, has emerged as pivotal factor modulating age-related changes liver. SIRT1 preserves function regulating essential aging-related pathways, including telomere maintenance, epigenetic modifications, senescence, intercellular communication, inflammation, mitochondrial function. Notably, levels naturally with age, contributing progression increased vulnerability injury. This review summarizes regulatory role aging its impact on diseases such fibrosis, alcoholic associated (ALD), metabolic dysfunction-associated steatotic (MASLD), steatohepatitis (MASH), hepatocellular carcinoma (HCC). We also discuss emerging therapeutic approaches, activators, gene therapy, nutritional interventions, which are evaluated their potential restore mitigate progression. Finally, we highlight future research directions optimize SIRT1-targeted therapies clinical applications conditions.

Language: Английский

Citations

1
Jagged-mediated development and disease: Mechanistic insights and therapeutic implications for Alagille syndrome DOI Creative Commons
J. Mašek, Emma Andersson

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 86, P. 102302 - 102302

Published: Jan. 9, 2024

Notch signaling controls multiple aspects of embryonic development and adult homeostasis. Alagille syndrome is usually caused by a single mutation in the jagged canonical ligand 1 (JAG1), manifests with liver disease cardiovascular symptoms that are direct consequence JAG1 haploinsufficiency. Recent insights into Jag1/Notch-controlled developmental homeostatic processes explain how pathology develops hepatic systems and, together recent elucidation mechanisms modulating regeneration, provide basis for therapeutic efforts. Importantly, presentation can be regulated genetic modifiers, may also therapeutically leverageable. Here, we summarize Jag1 relevance to syndrome, focused on Jag1/Notch functions

Language: Английский

Citations

8
Identification of STAT3 as a biomarker for cellular senescence in liver fibrosis: A bioinformatics and experimental validation study DOI Creative Commons

Xue Pang,

Shang Gao, Tao Liu

et al.

Genomics, Journal Year: 2024, Volume and Issue: 116(2), P. 110800 - 110800

Published: Jan. 28, 2024

Cellular senescence is associated with a dysregulated inflammatory response, which an important driver of the development liver fibrosis (LF). This study aimed to investigate effect cellular on LF and identify potential key biomarkers through bioinformatics analysis combined validation experiments in vivo vitro. The Gene Expression Omnibus (GEO) database GeneCards were used download dataset aging-related gene set, respectively. Functional enrichment differential genes was then performed using GO KEGG. Hub further screened Cytoscape's cytoHubba. Diagnostic values for hub evaluated receiver operating characteristic (ROC) curve. Next, CIBERSORTx estimate immune cell types ratios. Finally, vitro validated results analysis. Moreover, molecular docking simulate drug-gene interactions. A total 44 differentially expressed (AgDEGs) identified, showed that these mainly enriched responses. PPI network identified 6 AgDEGs (STAT3, TNF, MMP9, CD44, TGFB1, TIMP1), ROC they all have good diagnostic value. Immune infiltration suggested significantly M1 macrophages or other cells. Notably, STAT3 positively correlated α-SMA, COL1A1, IL-6 IL-1β, hepatocytes (HCs). Validation expression upregulated increased mice. co-culture system HCs hepatic stellate cells (HSCs) revealed inhibiting reduced suppressed HSCs activation. In addition, drug therapy target. may be involved promote activation, turn leads LF. Our findings suggest could biomarker

Language: Английский

Citations

5
Therapeutic potential of nicotinamide and ABT263 in alcohol‐associated liver disease through targeting cellular senescence DOI Creative Commons

Naheemat Modupeola Gold,

Qinchao Ding, Yang Yang

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(2)

Published: Feb. 1, 2025

Abstract Alcohol‐associated liver disease (ALD) is a major cause of liver‐related morbidity and mortality, yet clinically effective therapies for ALD remain lacking. Here, we demonstrate that alcohol intake its metabolite, acetaldehyde (ACH), induce senescence in the cells, respectively. To assess therapeutic potential targeting ALD, treated ALD‐affected mice with senolytic compound ABT263 senomorphic NAD + precursor, nicotinamide (NAM). The results show effectively clears senescent hepatocytes stellate reduces triglyceride (TG), but increases plasma alanine aminotransferase TG levels. Conversely, NAM efficiently suppresses senescence‐associated secretory phenotype (SASP), protecting from alcohol‐induced injury mice. RNA‐sequencing analysis revealed treatment downregulated genes involved adipogenesis while activating complement pathway. In contrast, upregulated metabolism‐related genes, such as Sirt1 , DNA damage marker including Rec8 E2f1 liver. These findings suggest cellular plays critical role injury. Compared cell clearance by ABT263, suppressing SASP may provide safer more approach ALD.

Language: Английский

Citations

0
Dihydromyricetin regulates the miR-155-5p/SIRT1/VDAC1 pathway to promote liver regeneration and improve alcohol-induced liver injury DOI Creative Commons
Qing Ma, Shuo Huang,

Mei-ya Li

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: 139, P. 156522 - 156522

Published: Feb. 16, 2025

Language: Английский

Citations

0
Senotherapeutic approach to age-related endocrine diseases DOI
Seda Turgut,

Gülnur Andican

Advances in pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
ADSCs attenuate Liver fibrosis via inducing HSC senescence: validation in dual-etiology models DOI Creative Commons

Mukexina Mulati,

Ning Yang,

Junlong Xue

et al.

PLoS neglected tropical diseases, Journal Year: 2025, Volume and Issue: 19(5), P. e0013094 - e0013094

Published: May 22, 2025

Background Liver fibrosis (LF) results from various causes, which require finding conserved mechanisms to help treat related diseases. Although adipose-derived stem cells (ADSCs) transplantation can alleviate hepatic fibrosis, their mechanism remains unclear. Accordingly, we explored the efficacy and behind ADSCs in two LF models. Methodology The carbon tetrachloride (CCl 4 )-induced liver injury Echinococcus multilocularis ( E. ) infection models were established, transplanted. Mouse samples harvested analyzed histologically. Expression levels of senescence-related proteins by immunohistochemistry. Hepatic stellate (HSCs) activation cell senescence protein expression evaluated via western blotting. Co-localization was determined immunofluorescence. To assess cellular degree, utilized senescence-associated β-galactosidase (SA-β-Gal) staining. Result In CCl -induced mouse model, surface exhibited a rough texture. hematoxylin eosin (H&E) staining revealed parenchymal destruction accompanied pseudolobule formation portal area. multiple white foci on surface. H&E massive inflammatory infiltration around with severe Sirius Red confirmed collagen deposition; both had elevated HSCs (α-SMA expression). After transplantation, deposition significantly diminished, while increased. Immunofluorescence co-localization p21 a-SMA showed that promoted activated (aHSCs). vitro co-culture similar results, changes TGF-β/Smad signaling inhibition. Conclusion Our findings indicate mitigate inducing aHSCs reducing production.

Language: Английский

Citations

0
Cellular Senescence in Acute Liver Injury: What Happens to the Young Liver? DOI Creative Commons

Keting He,

Diwenxin Zhou,

Zhangya Pu

et al.

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2024

Cellular senescence, characterized by irreversible cell cycle arrest, not only exists in age-related physiological states, but has been found to exist various diseases. It plays a crucial role both and pathological processes become trending topic global research recent years. Acute liver injury (ALI) high incidence worldwide, studies have shown that hepatic senescence can be induced following ALI. Therefore, we reviewed the significance of cellular To minimize potential confounding effects aging on ALI outcomes, selected involving young individuals identify characteristics senescent cells, value repair, its regulation mechanisms ALI, as biomarker for prospect treatment, future directions.

Language: Английский

Citations

3
Pulmonary fibrosis: from mechanisms to therapies DOI Creative Commons

Mengna Jiang,

Wenxia Bu,

Xuehai Wang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: May 8, 2025

Pulmonary fibrosis (PF) is a chronic, progressive interstitial lung disease characterized by excessive deposition of extracellular matrix (ECM) and abnormal fibroblast proliferation, which mainly caused air pollution, smoking, aging, occupational exposure, environmental pollutants microbial infections. Although antifibrotic agents such as pirfenidone nintedanib, approved the United States (US) Food Drug Administration (FDA), can slow decline in function progression, their side effects delivery inefficiency limit overall prognosis PF. Therefore, there an urgent need to develop effective therapeutic targets approaches for PF clinical settings. This review provides overview pathogenic mechanisms, drug targeting signaling pathways, promising strategies treating

Language: Английский

Citations

0
Cellular senescence and its pathogenic and therapeutic implications in autoimmune hepatitis DOI
Albert J. Czaja

Expert Review of Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Senescent cells are characterized by replicative arrest and phenotypes that produce diverse pro-inflammatory pro-oxidant mediators. The senescence of hepatic cell types could constitute an unrecognized pathogenic mechanism prognostic determinant in autoimmune hepatitis. impact cellular hepatitis is unknown, it may suggest adjunctive management strategies.

Language: Английский

Citations

1