Characterization of cellular senescence in doxorubicin-induced aging mice

Sun, Tianyue; Zhang, Lanxin; Feng, Jiali; Bao, Lingyuan; Wang, Jiqun; Song, Zhouzhi; Mao, Zhifan; Li, Jian; Hu, Zheyi

doi:10.1016/j.exger.2022.111800

Cited by 28 publications

(31 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, mitochondrial dysfunction plays an important role in aggravating cellular aging. Doxorubicin, a first‐line cancer treatment, has been shown to induce mitochondrial dysfunction and oxidative stress, consequently leading to cellular senescence 45,46 . As demonstrated in our previous studies, we treated Wharton's jelly‐derived mesenchymal stem cells with doxorubicin to induce mitochondrial dysfunction and oxidative stress in the present study 18 .…”

Section: Discussionmentioning

confidence: 79%

Ohwia caudata aqueous extract attenuates doxorubicin‐induced mitochondrial dysfunction in Wharton's jelly‐derived mesenchymal stem cells

Lee

Tsai

Sitorus

et al. 2023

Environmental Toxicology

View full text Add to dashboard Cite

Mitochondrial dysfunction has been linked to many diseases, including organ degeneration and cancer. Wharton's jelly‐derived mesenchymal stem cells provide a valuable source for stem cell‐based therapy and represent an emerging therapeutic approach for tissue regeneration. This study focused on screening the senomorphic properties of Ohwia caudata aqueous extract as an emerging strategy for preventing or treating mitochondrial dysfunction in stem cells. Wharton's jelly‐derived mesenchymal stem cells were incubated with 0.1 μM doxorubicin, for 24 h to induce mitochondrial dysfunction. Next, the cells were treated with a series concentration of Ohwia caudata aqueous extract (25, 50, 100, and 200 μg/mL) for another 24 h. In addition, an untreated control group and a doxorubicin‐induced mitochondrial dysfunction positive control group were maintained under the same conditions. Our data showed that Ohwia caudata aqueous extract markedly suppressed doxorubicin‐induced mitochondrial dysfunction by increasing Tid1 and Tom20 expression, decreased reactive oxygen species production, and maintained mitochondrial membrane potential to promote mitochondrial stability. Ohwia caudata aqueous extract retained the stemness of Wharton's jelly‐derived mesenchymal stem cells and reduced the apoptotic rate. These results indicate that Ohwia caudata aqueous extract protects Wharton's jelly‐derived mesenchymal stem cells against doxorubicin‐induced mitochondrial dysfunction and can potentially prevent mitochondrial dysfunction in other cells. This study provides new directions for the medical application of Ohwia caudata.

show abstract

Section: Discussionmentioning

confidence: 79%

Ohwia caudata aqueous extract attenuates doxorubicin‐induced mitochondrial dysfunction in Wharton's jelly‐derived mesenchymal stem cells

Lee

Tsai

Sitorus

et al. 2023

Environmental Toxicology

View full text Add to dashboard Cite

show abstract

“…ADR is an anthracycline antineoplastic drug widely used to construct a model of mouse cell senescence [ 20 ]. The β-galactosidase activity and pro-inflammatory cytokines IL-1 and IL-6 are consistently present in the senescence-associated secretory phenotype (SASP) [ 21 , 22 , 23 ].…”

Section: Resultsmentioning

confidence: 99%

The Expression Pattern of tRNA-Derived Small RNAs in Adult Drosophila and the Function of tRF-Trp-CCA-014-H3C4 Network Analysis

Yang

Xiao

Yuán

et al. 2023

IJMS

View full text Add to dashboard Cite

tRNA-derived small RNAs (tsRNAs) are derived from tRNA and include tRNA halves (tiRNAs) and tRNA fragments (tRFs). tsRNAs have been implicated in a variety of important biological functions, such as cell growth, transcriptional regulation, and apoptosis. Emerging evidence has shown that Ago1-guided and Ago2-guided tsRNAs are expressed at 3 and 30 days in Drosophila and that tRF biogenesis in fruit flies affects tRNA processing and tRNA methylation. However, a wide analysis of tsRNA patterns in different ages of Drosophila have not been reported via the small RNA sequencing method. In the present study, tsRNAs of young (7 days) and old (42 days) Drosophila were sequenced and their expression characteristics were analysed. Then, a specific tRF (named tRF-Trp-CCA-014) was determined and was found to be conserved in fruit flies, mice, and humans. The expression patterns of tRF-Trp-CCA-014 in different tissues and stages of fruit flies and mice, and mouse NIH/3T3 cells were detected. Furthermore, mouse embryonic fibroblast NIH/3T3 cells were used as a model to analyse the function and targets of tRF-Trp-CCA-014. The RNA-seq data of six groups (Mimics, Mimic NC, Inhibitors, Inhibitor NC, Aging (adriamycin), and Control (Normal)) in mouse NIH3T3 cells were analysed. The results showed that the number of tsRNAs at 42 days (417) was more than at 7 days (288); thus, it was enriched with age. tRFs-1 were the most enriched, followed by 5′-tRFs and 3′-tRFs. Twenty-one differentially expressed tsRNAs were identified between 7 days and 42 days. Then, the conserved tRF tRF-Trp-CCA-014 was identified and found to accumulate in aged fruit flies and aged mouse NIH3T3 cells. RNA-seq data showed that most differentially expressed genes were involved in the immune system, cancer: overview, and signal translation. Furthermore, tRF-Trp-CCA-014 was found to bind to the 3′UTR of H3C4 in a dual-luciferase reporter gene assay. tRF-Trp-CCA-014 and H3C4 were detected in the cytoplasm of aged NIH3T3 cells by RNA in situ hybridization. These results suggest that the H3C4 gene is the target of tRF-Trp-CCA-014. This study will advance the current understanding of tRF roles and their implication in Drosophila and mouse studies.

show abstract

“…Dox is a chemotherapeutic drug that can cause DNA damage to induce aging, and this Dox-induced aging serves as a common experimental model for mammalian premature aging [ 28 , 29 ]. Thus, this animal model was used further to evaluate the antiaging effect of HL0285.…”

Section: Resultsmentioning

confidence: 99%

“…The mechanism of the induction senescence is mainly due to the inhibition of DNA topoisomerase, which leads to DNA damage and triggers genomic instability [36][37][38]. Many studies have demonstrated that Dox-induced premature is manifested by a significant increase in senescence markers such as p21 WAF1/CIP1 , IL-6, γ-H2AX, and SA-β-Gal, accompanied by an increase in liver function indicators ALT and AST [29]. In this study, we found that HL0285 counteracted the upregulation of ALT, SA-β-Gal, and γH2AX in C57BL/6J mice with Dox-induced premature senescence (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Nicandra physalodes Extract Exerts Antiaging Effects in Multiple Models and Extends the Lifespan of Caenorhabditis elegans via DAF-16 and HSF-1

Wang

Huang

Shi

et al. 2022

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

The development of safe and effective therapeutic interventions is an important issue for delaying aging and reducing the risk of aging-related diseases. Chinese herbal medicines for the treatment of aging and other complex diseases are desired due to their multiple components and targets. Through screening for effects on lifespan of 836 Chinese herbal medicine extracts, Nicandra physalodes extract (HL0285) was found to exhibit lifespan extension activity in Caenorhabditis elegans (C. elegans). In further experiments, HL0285 improved healthspan, enhanced stress resistance, and delayed the progression of neurodegenerative diseases in C. elegans. Additionally, it ameliorated senescence in human lung fibroblasts (MRC-5 cells) and reversed liver function damage and reduced senescence marker levels in doxorubicin- (Dox-) induced aging mice. In addition, the longevity effect of HL0285 in C. elegans was dependent on the DAF-16 and HSF-1 signaling pathways, as demonstrated by the results of the mutant lifespan, gene level, and GFP level assays. In summary, we discovered that HL0285 had an antiaging effect in C. elegans, MRC-5 cells, and Dox-induced aging mice and deserves to be explored in the future studies on antiaging agents.

show abstract

Characterization of cellular senescence in doxorubicin-induced aging mice

Cited by 28 publications

References 46 publications

Ohwia caudata aqueous extract attenuates doxorubicin‐induced mitochondrial dysfunction in Wharton's jelly‐derived mesenchymal stem cells

Ohwia caudata aqueous extract attenuates doxorubicin‐induced mitochondrial dysfunction in Wharton's jelly‐derived mesenchymal stem cells

The Expression Pattern of tRNA-Derived Small RNAs in Adult Drosophila and the Function of tRF-Trp-CCA-014-H3C4 Network Analysis

Nicandra physalodes Extract Exerts Antiaging Effects in Multiple Models and Extends the Lifespan of Caenorhabditis elegans via DAF-16 and HSF-1

Contact Info

Product

Resources

About