Injectable Gene/Fiber‐Plexes Reverse Adipose Niche Senescence via Mito‐TERT Activation by Endogenous Mitochondrial Translocation DOI Open Access
Yijun Zhang, Jiahao He, Shifeng Ling

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Abstract Addressing adipose niche senescence is crucial for preventing obesity‐related aging. Telomerase reverse transcriptase (TERT) a promising target gene therapy, but traditional methods lack precision and safety. A novel mitochondrion‐located TERT (mito‐TERT) activating approach presented by injectable gene/short‐fiber complexes (gene/fiber‐plexes) to safely from mitochondrial enhancement. The gene/fiber‐plexes are prepared polydopamine‐coated short‐fibers adsorb cationic dendrimers (PAMAM G3, PG3) carrying plasmids Coenzyme Q10 (CoQ10), termed PG3‐TERT@CoQ10. Upon intraperitoneal injection, the adhere peritoneum release PG3‐TERT@CoQ10, precisely targeting niche. Transient active oxygen scavenging CoQ10 activates transfection endogenous mitochondrion translocation sequentially, enhancing function. In vitro in vivo studies shows that effectively targeted visceral tissue, increased mito‐TERT levels restored an obese mouse model, they tissue homeostasis metabolic stability. RNA sequencing indicated reduced senescence‐related genes cell cycle. This activation strategy great promise treating premature aging diseases linked senescence.

Language: Английский

Oscillatory Hypoxia Can Induce Senescence of Adipose-Derived Mesenchymal Stromal Cells Potentiating Invasive Transformation of Breast Epithelial Cells DOI Open Access
Ashkan Novin, Khadija H. Wali, Aditya Pant

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(5), P. 969 - 969

Published: Feb. 28, 2024

Obesity is strongly associated with occurrence, metastasis, and resistance to therapy in breast cancers, which also exhibit high adipose content the tumor microenvironment. Adipose tissue-derived mesenchymal stromal cells (ASCs) are recruited cancer by many mechanisms, including hypoxia, contribute metastatic transition of cancer. Breast cancers characterized regions can be temporally unstable owing a mismatch between oxygen supply consumption. Using high-sensitivity nanopatterned invasion assay, we found that ASCs could promote not only cell lines but MCF10A1, line derived from untransformed epithelium. RNA sequencing MCF10A1 conditioned medium revealed upregulation genes increased migration, chemotaxis, metastasis. Furthermore, fluctuating or oscillating hypoxia induce senescence ASCs, result an invasive potential treated cells. These findings highlight complex interplay within microenvironment, role transforming even non-cancerous epithelium toward phenotype, providing insights into early events.

Language: Английский

Citations

0
Epikardiales Fett: kardiovaskuläre Risiken und Manifestation einer veränderten Fettverteilung DOI
Paul Balfanz, Dirk Müller‐Wieland

Aktuelle Kardiologie, Journal Year: 2024, Volume and Issue: 13(04), P. 263 - 270

Published: July 31, 2024

Zusammenfassung Die Prävalenz einer chronischen Herzinsuffizienz (heart failure, HF) ist in der westlichen Bevölkerung sehr hoch. Bei HF spielen neben koronaren Herzerkrankung gerade bei den Patienten mit erhaltenen Pumpfunktion (Heart Failure with preserved Ejection Fraction, HFpEF) weitere metabolische Faktoren, wie z. B. Übergewicht und Diabetes, eine wichtige Rolle. Ektopes Fettgewebe, insbesondere epikardiales Fett (epicardial adipose tissue, EAT), könnte ein neues Bindeglied zwischen ischämischer inklusive Remodeling, Übergewicht/Adipositas Entwicklung HFpEF sein. EAT besitzt dichotome Funktion als Energiepuffer oder Risikofaktor Koronarkalzifizierung beeinflusst endokrines Gewebe durch Adipokine Adiponectin weiteren Krankheitsprogress nach Myokardinfarkt. Seneszenzvorgänge im Fettgewebe verändern dessen Verhalten sowie immunzelluläre Zusammensetzung, was auch die begünstigen könnte. Interessanterweise reduziert körperliche Aktivität Prozesse Seneszenz Gewichtsreduktion Menge an EAT.

Citations

0
Adipose tissue senescence: biological changes, hallmarks and therapeutic approaches DOI
Yajuan Zhang,

Yaoyao Jiang,

Xiaoyue Yang

et al.

Mechanisms of Ageing and Development, Journal Year: 2024, Volume and Issue: 222, P. 111988 - 111988

Published: Sept. 10, 2024

Language: Английский

Citations

0
Hypomethylation at PANDAR promoter progressively induces senescence in adipocyte precursor cells in subjects with obesity and type 2 diabetes DOI Creative Commons
Antonella Desiderio,

Monica Pastorino,

Michele Campitelli

et al.

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(19)

Published: Oct. 7, 2024

Abstract The risk of developing type 2 diabetes (T2D) is heterogeneous among individuals with obesity. Functional decline adipocyte precursor cells (APCs) and accumulation senescent in the subcutaneous adipose tissue contributes to progression toward T2D. LncRNAs regulate cell senescence may be implicated determining this abnormality APCs. Here, we report that APCs from obesity show a gradual increase multiple markers, which worsens parallel normal glucose tolerance (NGT) impaired (IGT) or Transcriptomic analysis identified PANDAR as top‐ranked lncRNA differentially expressed T2D non‐obese subjects. Q‐PCR confirmed up‐regulation obesity, at progressively increased levels those who developed, respectively, IGT Bisulfite sequencing luciferase assays revealed that, deterioration, −1317 CpG promoter became hypo‐methylated resulting enhanced induction by p53. silencing caused repression programs cycle re‐entry. transcription white blood (WBCs) mirrored Also, exhibited rescue WBCs following bariatric surgery, accompanied methylation regulatory CpG. In conclusion, dysregulation newly mechanism early along future, targeting represent valuable strategy delay progression.

Language: Английский

Citations

0
Injectable Gene/Fiber‐Plexes Reverse Adipose Niche Senescence via Mito‐TERT Activation by Endogenous Mitochondrial Translocation DOI Open Access
Yijun Zhang, Jiahao He, Shifeng Ling

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Abstract Addressing adipose niche senescence is crucial for preventing obesity‐related aging. Telomerase reverse transcriptase (TERT) a promising target gene therapy, but traditional methods lack precision and safety. A novel mitochondrion‐located TERT (mito‐TERT) activating approach presented by injectable gene/short‐fiber complexes (gene/fiber‐plexes) to safely from mitochondrial enhancement. The gene/fiber‐plexes are prepared polydopamine‐coated short‐fibers adsorb cationic dendrimers (PAMAM G3, PG3) carrying plasmids Coenzyme Q10 (CoQ10), termed PG3‐TERT@CoQ10. Upon intraperitoneal injection, the adhere peritoneum release PG3‐TERT@CoQ10, precisely targeting niche. Transient active oxygen scavenging CoQ10 activates transfection endogenous mitochondrion translocation sequentially, enhancing function. In vitro in vivo studies shows that effectively targeted visceral tissue, increased mito‐TERT levels restored an obese mouse model, they tissue homeostasis metabolic stability. RNA sequencing indicated reduced senescence‐related genes cell cycle. This activation strategy great promise treating premature aging diseases linked senescence.

Language: Английский

Citations

0