ARMH4 accelerates aging by maintaining a positive-feedback growth signaling circuit DOI Creative Commons
Wang Zh, Fang Yu, Binhui Wang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

Abstract Aging is an inevitable process integrating chronological alterations of multiple organs. A growing aging population necessitates feasible anti-aging strategies to deal with age-associated health problems. We previously performed a proteomics analysis in healthy-aging cohort, and revealed age-related downregulation ARMH4. Here we generated whole-body Armh4-knockout mouse line, investigated its impact on systemic aging. Under normal feeding conditions, Armh4 deficiency significantly lowered spontaneous mortality extended maximum lifespan. In the female mice, postponed sexual maturity for one week. At organ level, pathologies heart, liver, kidney, spleen were substantially alleviated by deletion. Mechanistically, ARMH4 interacted IGF1R/FGFR1 sensitize activation PI3K-AKT-mTORC1 Ras-MEK-ERK pathways, consequently promoting protein synthesis inhibiting autophagy. Moreover, was required maintenance expressions through regulating transcription factor c-Myc. Therefore, maintains positive-feedback growth signaling promote

Language: Английский

JAG1/Notch Pathway Inhibition Induces Ferroptosis and Promotes Cataractogenesis DOI Open Access
Yewen Ni, Liangping Liu, Fanying Jiang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 307 - 307

Published: Jan. 1, 2025

Cataracts remain the leading cause of visual impairment worldwide, yet underlying molecular mechanisms, particularly in age-related cataracts (ARCs), are not fully understood. The Notch signaling pathway, known for its critical role various degenerative diseases, may also contribute to ARC pathogenesis, although specific involvement is unclear. This study investigates regulating ferroptosis lens epithelial cells (LECs) and impact on progression. RNA sequencing anterior capsule samples from patients revealed a significant downregulation signaling, coupled with an upregulation ferroptosis-related genes. Notch1 expression decreased, while markers increased age-dependent manner. In vitro, alleviated by decreasing ferritin heavy chain 1 (FTH1) p53 levels enhancing nuclear factor erythroid 2-related 2 (Nrf2), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11). Conversely, inhibition exacerbated ferroptosis, as evidenced reduced Nrf2, GPX4, SLC7A11 expression. These findings suggest that promotes LECs impairing Nrf2/GPX4 antioxidant thereby contributing development. offers new insights into pathogenesis highlights pathway potential therapeutic target preventing or mitigating

Language: Английский

Citations

0
Is the liver resilient to the process of ageing? DOI Creative Commons
Nirupama Chatterjee, Rishabh Sharma,

Pratibha R Kale

et al.

Annals of Hepatology, Journal Year: 2024, Volume and Issue: unknown, P. 101580 - 101580

Published: Sept. 1, 2024

Language: Английский

Citations

4
Human Milk Oligosaccharides Ameliorate Intestinal Barrier in Aging Honey Bee by Regulating Gut Microbiota DOI
Xiaodong Lin, Yingying Lin, Yueyi Wang

et al.

Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 105954 - 105954

Published: Jan. 1, 2025

Language: Английский

Citations

0
Macrophage co-culture promotes cell reprogramming and prevents ferroptosis in aging fibroblasts for neurodegeneration therapy DOI

Lunjie Ma,

Fei Fang, Haonan Wang

et al.

Journal of Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
18F-FDG PET/CT predicts the prognosis of patients with hepatocellular carcinoma undergoing liver transplantation DOI Creative Commons
Wen-Jing Zheng, Yang Xu,

Hui Shan Tan

et al.

Liver Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 27

Published: March 5, 2025

In addition to radical resection, liver transplantation (LTx) is an effective treatment for hepatocellular carcinoma (HCC). However, tumor recurrence limits the efficacy of LTx in some patients. This study investigated role 18F-fludeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) predicting prognosis patients with HCC after LTx. A total 278 consecutive who underwent pre-LTx PET/CT were divided into derivation (n = 178) and temporal validation 100) cohorts evaluated values, immunohistochemical (IHC) findings, DNA sequencing tissues. Patients post-LTx exhibited significantly higher maximum standardized uptake values (SUVmax) scans. Receiver operating characteristic curve analyses identified SUVmax ratio (TSUVmax/LSUVmax) as strongest predictor recurrence, optimal cutoff value 1.43. Kaplan-Meier demonstrated that a TSUVmax/LSUVmax >1.43 was associated shorter time (TTR) overall survival (OS) both (p < 0.001 both). Multivariate Cox regression confirmed independent risk factor cohorts. IHC revealed correlated Ki-67 CK19 expression. indicated tumors had more mutations TMB. Furthermore, TP53, EPPK1, MDM4, SLAMF7, SDHC, B4GALT3, RXRG, FCGR family genes, well TP53 PI3K signaling-related alterations. The preoperative potential following Its use improves candidate selection management.

Language: Английский

Citations

0
Proteomic and phosphoproteomic signatures of aging mouse liver DOI
Rodrigo Mohallem, Allison J. Schaser, Uma K. Aryal

et al.

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

Published: March 14, 2025

Language: Английский

Citations

0
Targeting senescent hepatocytes for treatment of metabolic dysfunction-associated steatotic liver disease and multi-organ dysfunction DOI Creative Commons
Kuo Du, David S. Umbaugh, Liuyang Wang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 28, 2025

Senescent hepatocytes accumulate in metabolic dysfunction-associated steatotic liver disease (MASLD) and are linked to worse clinical outcomes. However, their heterogeneity lack of specific markers have made them difficult target therapeutically. Here, we define a senescent hepatocyte gene signature (SHGS) using vitro vivo models show that it tracks with MASLD progression/regression across mouse large human cohorts. Single-nucleus RNA-sequencing functional studies reveal SHGS+ originate from p21+ cells, lose key functions release factors drive progression. One such factor, GDF15, increases circulation alongside burden Through chemical screening, identify senolytics selectively eliminate improve male mice. Notably, SHGS enrichment also correlates dysfunction other organs. These findings establish as drivers highlight potential therapeutic strategy for targeting cells beyond.

Language: Английский

Citations

0
Inhibition of Ferroptosis Delays Aging and Extends Healthspan Across Multiple Species DOI Creative Commons
Haijun Fu,

Xing‐Yue Zhou,

Dalian Qin

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Abstract Ferroptosis, a form of iron‐dependent cell death, plays pivotal role in age‐related diseases; yet, its impact on cellular senescence and healthspan mammals remains largely unexplored. This study identifies ferroptosis as key regulator senescence, showing that inhibition can significantly delay aging extend across multiple species. During is progressively exacerbated, marked by increased lipid peroxidation, oxidative stress, diminished glutathione peroxidase 4 (GPX4) levels. Ferroptosis inducers such Erastin RSL3 accelerate senescence; while, inhibitors liproxstatin‐1 (Lip‐1) ferrostatin‐1 (Fer‐1) effectively mitigate both chemically replicatively induced senescence. In vivo, Fer‐1 extends lifespan Caenorhabditis elegans , enhances motor function, preserves tissue integrity, mitigates cognitive decline prematurely naturally aged mice. These effects are attributed to Fer‐1's upregulation GPX4 ferroptosis. Notably, long‐term treatment (over 6 months) does not adversely affect body weight or induce aging‐related damage but rejuvenates hematological parameters. findings establish critical player dynamics highlight promising strategy lifespan, providing valuable insights for translational approaches combat decline.

Language: Английский

Citations

0
Associations of non-essential metal/metalloids and their mixture with liver function in Chinese older adults: the mediating roles of lipid profiles DOI

Xuqiu Cheng,

Wenyuan Liu, Ziwei Tian

et al.

Environmental Pollution, Journal Year: 2025, Volume and Issue: unknown, P. 126207 - 126207

Published: April 1, 2025

Language: Английский

Citations

0
Hepatic-specific vitamin D receptor downregulation alleviates aging-related metabolic dysfunction-associated steatotic liver disease DOI
Feng Zhu, Bei Lin,

Shi-Hua Lin

et al.

World Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: 31(14)

Published: April 9, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by the abnormal lipid deposition in hepatocytes. The prevalence of MASLD significantly increased elderly population, suggesting that aging may be related to occurrence MASLD. Emerging evidences suggest vitamin D receptor (VDR) implicated progression Therefore, additional researches are warranted elucidate whether VDR plays a role aging-related To investigate relationship between and explore mechanisms Cellular senescence models were established, phenotype telomerase RNA component knockout mice was validated. These then used as model for subsequent studies. Changes expression livers examined. knockdown models, including cell hepatic-specific mice, constructed, established these models. Additionally, (VD)-supplemented senescent lines constructed. steatosis cells more severe than normal (P < 0.05). Moreover, hepatic pronounced compared control group when successfully induced we concluded aggravated steatosis. after aging. alleviated When stimulated with VD, cellular However, VD supplementation had no effect on mice. Aging can lead steatosis, could serve potential molecular target

Language: Английский

Citations

0