AI Article Synopsis
- - Metformin has a potential anti-aging effect on vascular smooth muscle cells (VSMCs) by enhancing autophagy, which may combat cellular senescence and improve vascular health in aging and related diseases.
- - In experiments with animal models and elderly human VSMCs, metformin treatment reduced senescence markers and improved arterial stiffness while promoting the proliferation and migration of senescent VSMCs.
- - The study suggests that metformin achieves these anti-senescence effects by restoring autophagic activity, specifically by enhancing autophagosome-lysosome fusion, which is crucial for cellular rejuvenation.
Article Abstract
Introduction: Vascular smooth muscle cell (VSMC) senescence in the vasculature results in vascular aging as well as age-related diseases, while metformin improves the inflamm-aging profile by enhancing autophagy. However, metformin's impact on VSMC senescence is largely undefined.
Objectives: To test the hypothesis that metformin exerts an anti-senescence role by restoring autophagic activity in VSMCs and vascular tissues.
Methods: Animal models established by angiotensin II (Ang II) induction and physiological aging and senescent primary VSMCs from the aortas of elderly patients were treated with metformin. Cellular and vascular senescence were assessed by measuring the amounts of senescence-associated β-galactosidase and senescence markers, including p21 and p53. Autophagy levels were assessed by autophagy-related protein expression, transmission electron microscope, and autolysosome staining. In order to explore the underlying mechanism of the anti-senescence effects of metformin, 4D label-free quantitative proteomics and bioinformatic analyses were conducted, with subsequent experiments validating these findings.
Results: Ang II-dependent senescence was suppressed by metformin in VSMCs and vascular tissues. Metformin also significantly improved arterial stiffness and alleviated structural changes in aged arteries, reduced senescence-associated secretory phenotype (SASP), and improved proliferation and migration of senescent VSMCs. Mechanistically, the proteomic analysis indicated that autophagy might contribute to metformin's anti-senescence effects. Reduced autophagic flux was observed in Ang II-induced cellular and vascular senescence; this reduction was reversed by metformin. Specifically, metformin enhanced the autophagic flux at the autophagosome-lysosome fusion level, whereas blockade of autophagosome-lysosome fusion inhibited the anti-senescence effects of metformin.
Conclusions: Metformin prevents VSMC and vascular senescence by promoting autolysosome formation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637479 | PMC |
| http://dx.doi.org/10.1016/j.jare.2021.12.009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ubiquitination of TFEB increased intestinal permeability to aggravate metabolic dysfunction-associated steatohepatitis.
Hepatology
January 2025
China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
Background And Aims: Increased intestinal permeability exacerbates the development of metabolic dysfunction associated steatohepatitis (MASH), but the underlying mechanisms remain unclear. Autophagy is important for maintaining normal intestinal permeability. Here, we investigated the impact of intestinal transcription factor EB (TFEB), a key regulator of autophagy, in intestinal permeability and MASH progression.
View Article and Find Full Text PDFMaternal Exposure to Polystyrene Nanoplastics Disrupts Spermatogenesis in Mouse Offspring by Inducing Overexpression in Undifferentiated Spermatogonia.
ACS Nano
January 2025
School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200241, China.
Undifferentiated spermatogonia (Undiff-SPG) plays a critical role in maintaining continual spermatogenesis. However, the toxic effects and molecular mechanisms of maternal exposure to nanoplastics on offspring Undiff-SPG remain elusive. Here, we utilized a multiomics combined cytomorphological approach to explore the reproductive toxicity and mechanisms of polystyrene nanoplastics (PS-NPs) on offspring Undiff-SPG in mice after maternal exposure.
View Article and Find Full Text PDFHigh glucose induces renal tubular epithelial cell senescence by inhibiting autophagic flux.
Hum Cell
January 2025
Department of Nephrology, Zhong Da Hospital, Gulou District, No. 87, Dingjiaqiao, Zhongyangmen Street, Nanjing, 210009, Jiangsu, China.
Autophagy, a cellular degradation process involving the formation and clearance of autophagosomes, is mediated by autophagic proteins, such as microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (p62), and modulated by 3-methyladenine (3-MA) as well as chloroquine (CQ). Senescence, characterised by permanent cell cycle arrest, is marked by proteins such as cyclin-dependent kinase inhibitor 1 (p21) and tumour protein 53 (p53). This study aims to investigate the relationship between cell senescence and renal function in diabetic kidney disease (DKD) and the effect of autophagy on high-glucose-induced cell senescence.
View Article and Find Full Text PDFAutophagy intersection: Unraveling the role of the SNARE complex in lysosomal fusion in Alzheimer's disease.
J Alzheimers Dis
January 2025
School of Medicine, Chongqing University, Chongqing, P.R. China.
Autophagy is a fundamental cellular process critical for maintaining neuronal health, particularly in the context of neurodegenerative diseases such as Alzheimer's disease (AD). This review explores the intricate role of the SNARE complex in the fusion of autophagosomes with lysosomes, a crucial step in autophagic flux. Disruptions in this fusion process, often resulting from aberrant SNARE complex function or impaired lysosomal acidification, contribute to the pathological accumulation of autophagosomes and lysosomes observed in AD.
View Article and Find Full Text PDFActivation of the muscle‐to‐brain‐axis reduces amyloid plaque accumulation and rescues behavioral deficits by enhancing synaptic integrity and neurotrophic signaling in a mouse model of Alzheimer’s disease.
Alzheimers Dement
December 2024
USC Leonard Davis School of Gerontology, Los Angeles, CA, USA
Background: Alzheimer’s disease (AD) is associated with complex pathophysiology including synaptic dysregulation, compromised neurotrophic signaling, deficits in autophagic flux and neuroinflammation). Skeletal muscle regulates many brain functions relevant to aging, by activating the muscle‐to‐brain axis through the secretion of skeletal muscle originating factors (myokines) with cellular‐modifying, neuro and geroprotective properties. Our group developed transgenic mice that overexpress the skeletal muscle human Transcription Factor EB (TFEB), a master regulator of lysosomal‐to‐nucleus signaling, resulting in enhanced proteostasis and neuroprotection in a Tau mouse model.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!