Fisetin suppresses chondrocyte senescence and attenuates osteoarthritis progression by targeting SIRT6 DOI Creative Commons
Xuezhong Wang, Xuyang Li, Jianlin Zhou

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 20, 2023

Abstract Background Osteoarthritis (OA), the most common type of arthritis, is a highly prevalent age-related joint disease particularly in subjects over 65 years old. The chronic rise senescent cells closely correlates with diseases including OA, and senescence-associated secretory phenotype (SASP) implicated pathogenesis OA cartilage degeneration. Sirtuin 6 (SIRT6) probable to be key senescence-related regulator. Fisetin (FST), natural flavonol flavonoid family, recommended senolytic that extends health lifespan. However, potential chondroprotective effects FST on rats remain largely unclarified. This study aimed investigate ameliorative relationship SIRT6, detailed mechanisms from both anti-inflammatory anti-senescent perspectives. Methods Rats were subjected destabilization medial meniscus (DMM) surgery induce experimental model vivo. Chondrocytes treated IL-1β utilized mimic cell vitro. Intra-articular injection FST, OSS_128167 (OSS, SIRT6 inhibitor), MDL800 (MDL, agonist) vivo or incubation IL-1β-induced rat chondrocytes vitro performed determine link SIRT6. Results level was negatively correlated severity. downregulation validated cartilages DMM IL-1β-treated chondrocytes. Of note, We demonstrated could activate Both administration activation using MDL rescued erosion, decreased extracellular matrix (ECM) degradation, prevented apoptosis, improved detrimental phenotype. alleviative against inflammation, ECM senescence also confirmed IL-1β-stimulated Conclusion loss occurs articular which linked aging. attenuates injury-induced aging-related changes by targeting

Language: Английский

Cellular senescence and SASP in tumor progression and therapeutic opportunities DOI Creative Commons

Zening Dong,

Yahan Luo,

Zhangchen Yuan

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 31, 2024

Cellular senescence (CS), a permanent and irreversible arrest of the cell cycle proliferation leading to degeneration cellular structure function, has been implicated in various key physiological pathological processes, particularly cancer. Initially, CS was recognized as barrier tumorigenesis, serving an intrinsic defense mechanism protect cells from malignant transformation. However, increasing evidence suggests that senescent can promote tumor progression overt malignancy, primarily through set factors known senescence-associated secretory phenotypes (SASPs), including chemokines, growth factors, cytokines, stromal metalloproteinases. These significantly reshape microenvironment (TME), enabling tumors evade immune destruction. Interestingly, some studies have also suggested SASPs may impede development by enhancing immunosurveillance. opposing roles highlight complexity heterogeneity diverse cancers. Consequently, there growing interest pharmacological interventions targeting or cancer therapy, such senolytics senomorphics, either clearance mitigate harmful effects SASPs. In this review, we will interpret concept CS, delve into role reshaping TME, summarize recent advances anti-tumor strategies

Language: Английский

Citations

31
Research progress of interleukin-15 in cancer immunotherapy DOI Creative Commons

Menghan Cai,

Xuan Huang,

Xiting Huang

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: May 12, 2023

Interleukin-15 (IL-15) is a cytokine that belongs to the interleukin-2 (IL-2) family and essential for development, proliferation, activation of immune cells, including natural killer (NK) T cells B cells. Recent studies have revealed interleukin-15 also plays critical role in cancer immunotherapy. agonist molecules shown agonists are effective inhibiting tumor growth preventing metastasis, some undergoing clinical trials. In this review, we will summarize recent progress research over past 5 years, highlighting its potential applications immunotherapy development.

Language: Английский

Citations

41
Fisetin suppresses chondrocyte senescence and attenuates osteoarthritis progression by targeting sirtuin 6 DOI
Xuezhong Wang, Xuyang Li, Jianlin Zhou

et al.

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 390, P. 110890 - 110890

Published: Jan. 24, 2024

Language: Английский

Citations

11
Immunotherapeutic approach to reduce senescent cells and alleviate senescence‐associated secretory phenotype in mice DOI Creative Commons
Niraj Shrestha,

Pallavi Chaturvedi,

Xiaoyun Zhu

et al.

Aging Cell, Journal Year: 2023, Volume and Issue: 22(5)

Published: March 26, 2023

Abstract Accumulation of senescent cells (SNCs) with a senescence‐associated secretory phenotype (SASP) has been implicated as major source chronic sterile inflammation leading to many age‐related pathologies. Herein, we provide evidence that bifunctional immunotherapeutic, HCW9218, capabilities neutralizing TGF‐β and stimulating immune cells, can be safely administered systemically reduce SNCs alleviate SASP in mice. In the diabetic db/db mouse model, subcutaneous administration HCW9218 reduced islet β resulting improved glucose tolerance, insulin resistance, aging index. naturally aged mice, durably level SASP, lower expression pro‐inflammatory genes peripheral organs. treatment also reverted pattern key regulatory circadian gene mice levels observed young impacted associated metabolism fibrosis liver. Single‐nucleus RNA Sequencing analysis further revealed differentially changed transcriptomic landscape hepatocyte subtypes involving metabolic, signaling, cell‐cycle, pathways Long‐term survival studies showed physical performance without compromising health span Thus, represents novel immunotherapeutic approach clinically promising new class senotherapeutic agents targeting cellular diseases.

Language: Английский

Citations

17
Therapeutic approaches targeting aging and cellular senescence in Huntington's disease DOI Creative Commons
Asif Ahmad Bhat, Ehssan Moglad, Muhammad Afzal

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(10)

Published: Oct. 1, 2024

Huntington's disease (HD) is a devastating neurodegenerative that manifested by gradual loss of physical, cognitive, and mental abilities. As the advances, age has major impact on pathogenic signature mutant huntingtin (mHTT) protein aggregation. This review aims to explore intricate relationship between aging, mHTT toxicity, cellular senescence in HD. Scientific data interplay mHTT, HD were collected from several academic databases, including PubMed, Google Scholar, Google, ScienceDirect. The search terms employed "AGING," "HUNTINGTON'S DISEASE," "MUTANT HUNTINGTIN," "CELLULAR SENESCENCE." Additionally, gather information molecular mechanisms potential therapeutic targets, was extended include relevant such as "DNA DAMAGE," "OXIDATIVE STRESS," "AUTOPHAGY." According research, aging leads worsening pathophysiology through some processes. result accumulation, promoted, which causes DNA damage, oxidative stress, decreased autophagy, increased inflammatory responses. Pro-inflammatory cytokines other substances are released senescent cells, may worsen neuronal damage course disease. It been shown treatments directed at these pathways reduce symptoms enhance longevity experimental animals, pointing new possibility treating condition. Through their amplification harmful effects play crucial roles development Comprehending interplays creates novel opportunities for measures targeted alleviating enhancing patients' quality life.

Language: Английский

Citations

6
Temozolomide promotes matrix metalloproteinase 9 expression through p38 MAPK and JNK pathways in glioblastoma cells DOI Creative Commons

Hien Duong Thanh,

Sueun Lee, Nguyễn Thị Thanh Thùy

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 21, 2024

Abstract Glioblastoma (GBM) is a highly aggressive and deadly brain cancer. Temozolomide (TMZ) the standard chemotherapeutic agent for GBM, but majority of patients experience recurrence invasion tumor cells. We investigated whether TMZ treatment GBM cells regulates matrix metalloproteinases (MMPs), which have main function to promote cell invasion. effectively killed GL261, U343, U87MG at concentration 500 µM, surviving upregulated MMP9 expression its activity not those MMP2. also elevated levels mRNA promoter activity. Subcutaneous graft tumors survived from exhibited increased enhanced gelatinolytic TMZ-mediated upregulation was specifically mediated through phosphorylation p38 JNK. This then stimulates AP-1 c-Fos c-Jun. Inhibition p38, JNK, or both pathways counteracted TMZ-induced AP-1. study proposes potential adverse effect GBM: potentially associated with poor prognosis. provides valuable insights into molecular mechanisms by leads in

Language: Английский

Citations

4
Metabolic dysfunction−associated liver disease and diabetes: Matrix remodeling, fibrosis, and therapeutic implications DOI
Weiguo Fan,

Toby M. Bradford,

Natalie J. Török

et al.

Annals of the New York Academy of Sciences, Journal Year: 2024, Volume and Issue: 1538(1), P. 21 - 33

Published: July 12, 2024

Abstract Metabolic dysfunction−associated liver disease (MASLD) and steatohepatitis (MASH) are becoming the most common causes of chronic in United States worldwide due to obesity diabetes epidemics. It is estimated that by 2030 close 100 million people might be affected patients with type 2 especially at high risk. Twenty 30% MASLD can progress MASH, which characterized steatosis, necroinflammation, hepatocyte ballooning, advanced cases, fibrosis progressing cirrhosis. Clinically, it recognized progression diabetic accelerated role various genetic epigenetic factors, as well cell–matrix interactions stromal remodeling, have recently been recognized. While there has great drug development clinical trials for MASLD/MASH, complexity these pathways highlights need improve diagnosis/early detection develop more successful antifibrotic therapies not only prevent but reverse fibrosis.

Language: Английский

Citations

4
The role of the circadian timing system in sarcopenia in old age: a scoping review DOI Creative Commons
Francesco Palmese, Ylenia Druda, Rossella Del Toro

et al.

European Geriatric Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

Citations

0
Circadian Rhythm, Hypoxia, and Cellular Senescence: From Molecular Mechanisms to Targeted Strategies DOI

Tong Nie,

Eugenie Nepovimová, Qinghua Wu

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177290 - 177290

Published: Jan. 1, 2025

Language: Английский

Citations

0
The context-dependent effect of cellular senescence: from embryogenesis and wound healing to aging DOI

Rupa Lavarti,

Tatiana Alvarez‐Diaz,

K. Marti

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102760 - 102760

Published: May 1, 2025

Language: Английский

Citations

0