Cellular Senescence and Ageing: Mechanisms and Interventions

Mylonas, Andreas; O’Loghlen, Ana

doi:10.3389/fragi.2022.866718

Cited by 55 publications

(51 citation statements)

References 84 publications

(111 reference statements)

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“…In addition, cellular senescence can be triggered by various intrinsic and extrinsic stimuli, as well as developmental signals, whereby the types of senescence mainly include replicative senescence (RS), oncogene-induced senescence (OIS), stress-induced premature senescence (SIPS), and developmental senescence (DS) (Mylonas & O'Loghlen, 2022;Zhou et al, 2020). In this study, GA-D showed significant protective effects against MSCs senescence induced by In conclusion, our results demonstrated that GA-D protects hAMSCs against H 2 O 2 -induced senescence by targeting 14-3-3ε to activate the CaM/CaMKII and Nrf2/HO-1/NQO1 signaling pathways (Figure S7).…”

Section: Discussionmentioning

confidence: 99%

Ganoderic acid D prevents oxidative stress‐induced senescence by targeting 14‐3‐3ε to activate CaM/CaMKII/NRF2 signaling pathway in mesenchymal stem cells

Yuan

Luo

et al. 2022

Aging Cell

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Section: Discussionmentioning

confidence: 99%

Ganoderic acid D prevents oxidative stress‐induced senescence by targeting 14‐3‐3ε to activate CaM/CaMKII/NRF2 signaling pathway in mesenchymal stem cells

Yuan

Luo

et al. 2022

Aging Cell

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“…Aging is characterized by the accumulation of damage to macromolecules and cell architecture resulting in a progressive decrease in the function of tissue and organ due to nutrition, genetic and environmental factors, and lifestyle [ 28 ]. The accumulation of these damaged arrested cells was observed with the increase in age [ 29 ], and these senescent cells were noted to contribute to diseases that are related to aging, such as renal damage [ 30 ], alcoholic fatty liver disease [ 31 ], cerebrovascular disorders [ 32 ], diabetes [ 12 ], and Alzheimer's disease [ 33 ]. Cellular senescence is an inherent process that inhibits tumor progression, contributing to arresting the cells autonomously in the cell cycle and preventing further divisions.…”

Section: Discussionmentioning

confidence: 99%

Identification and Development of an Age-Related Classification and Signature to Predict Prognosis and Immune Landscape in Osteosarcoma

Hong

et al. 2022

Journal of Oncology

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Background. In childhood and adolescence, the prevailing bone tumor is osteosarcoma associated with frequent recurrence and lung metastasis. This research focused on predicting the survival and immune landscape of osteosarcoma by developing a prognostic signature and establishing aging-related genes (ARGs) subtypes. Methods. The training group comprised of the transcriptomic and associated clinical data of 84 patients with osteosarcoma accessed at the TARGET database and the validation group consisted of 53 patients from GSE21257. The aging-related subtypes were identified using unsupervised consensus clustering analysis. The ARG signature was developed utilizing multivariate Cox analysis and LASSO regression. The prognostic value was assessed using the univariate and multivariate Cox analyses, Kaplan-Meier plotter, time-dependent ROC curve, and nomogram. The functional enrichment analyses were performed by GSEA, GO, and KEGG analysis, while the ssGSEA, ESTIMATE, and CIBERSORT analyses were conducted to reveal the immune landscape in osteosarcoma. Results. The two clusters of osteosarcoma patients formed based on 543 ARGs, depicted a considerable difference in the tumor microenvironment, and the overall survival and immune cell infiltration rate varied as well. Among these, the selected 23 ARGs were utilized for the construction of an efficient predictive prognostic signature for the overall survival prediction. The testing in the validation group of osteosarcoma patients confirmed the status of the high-risk score as an independent indicator for poor prognosis, which was already identified as such using the univariate and multivariate Cox analyses. Furthermore, the ARG signature could distinguish different immune-related functions, infiltration status of immune cells, and tumor microenvironment, as well as predict the immunotherapy response of osteosarcoma patients. Conclusion. The aging-related subtypes were identified and a prognostic signature was developed in this research, which determined different prognoses and allowed for treatment of osteosarcoma patients to be tailored. Additionally, the immunotherapeutic response of individuals with osteosarcoma could also be predicted by the ARG signature.

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“…Accumulation of DNA in the cytoplasm serves as a potent danger signal that can activate an innate immunity cytosolic DNA sensing pathway, leading to proinflammatory responses. In fact, SASP is associated with various growth-regulatory factors, cytokines, and chemokines (Krtolica et al, 2001; Mylonas & O’Loghlen, 2022). We found a significant increase in secreted soluble factors such as IL-1α, IL-6, and MIP-1α in aged mouse urines and tissues.…”

Section: Discussionmentioning

confidence: 99%

D-mannose ameliorates age-associated cellular senescence in the bladder urothelium and NLRP3/Gasdermin/IL-1β -driven pyroptotic epithelial cell shedding

Joshi

Salazar

Wang

et al. 2022

Preprint

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Aging is a risk factor for disease via increased susceptibility to infection, decreased ability to maintain homeostasis, inefficiency in combatting stress, and decreased regenerative capacity. Multiple diseases including urinary tract infection (UTI), are more prevalent with age; however, the mechanisms underlying how aging affects the urinary tract mucosa and the reason why aging correlates with disease are poorly understood. Here, we show that, relative to young (8-12 weeks) mice, the urothelium of aged (18-24 months) female mice accumulates large lysosomes with decreased acid phosphatase activity and shows overall decreased autophagic flux. Aged bladders exhibit basally high accumulation of reactive oxygen species (ROS) and dampened redox response. Furthermore, the aged urothelium exhibits a canonical senescence-associated secretory phenotype (SASP) at baseline with continuous NLRP3-inflammasome- and Gasdermin D (GSDMD)-dependent pyroptotic cell death. Accordingly, we find that aged mice chronically exfoliate epithelial cells. When infected with uropathogenic E. coli, infected aged mice harbor more bacterial reservoirs post-infection and are prone to spontaneous recurrent UTI. Finally, treatment of aged mice with D-Mannose, a natural bioactive monosaccharide, rescues autophagy flux, reverses SASP, and limits pyroptotic epithelial shedding. Thus, normal aging dramatically affects bladder physiology with aging alone increasing baseline cellular stress and susceptibility to infection. Additionally, our results suggest that mannose supplementation could serve as a senotherapeutic to limit age-associated urothelial dysfunction.

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Cellular Senescence and Ageing: Mechanisms and Interventions

Cited by 55 publications

References 84 publications

Ganoderic acid D prevents oxidative stress‐induced senescence by targeting 14‐3‐3ε to activate CaM/CaMKII/NRF2 signaling pathway in mesenchymal stem cells

Ganoderic acid D prevents oxidative stress‐induced senescence by targeting 14‐3‐3ε to activate CaM/CaMKII/NRF2 signaling pathway in mesenchymal stem cells

Identification and Development of an Age-Related Classification and Signature to Predict Prognosis and Immune Landscape in Osteosarcoma

D-mannose ameliorates age-associated cellular senescence in the bladder urothelium and NLRP3/Gasdermin/IL-1β -driven pyroptotic epithelial cell shedding

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