Systemic induction of senescence in young mice after single heterochronic blood exchange

Jeon, Ok Hee; Mehdipour, Melod; Gil, Tae-Hwan; Kang, Minha; Aguirre, Nicholas W.; Robinson, Zachery; Kato, Cameron; Etienne, Jessy; Lee, Hyo Gyeong; Alimirah, Fatouma; Walavalkar, Vighnesh; Desprez, Pierre-Yves; Conboy, Michael J.; Campisi, Judith; Conboy, Irina M.

doi:10.1038/s42255-022-00609-6

Cited by 54 publications

(42 citation statements)

References 45 publications

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“…Remarkably, EV senescent cells-derived can contribute to the induction of cellular senescence in normal cells through a mechanism mediated by IFN-induced transmembrane protein 3 (IFITM3), which is elevated in EVs from elderly donors compared with EVs isolated from young donors [ 194 ]. According to these observations, several studies have demonstrated that a small number of EVs derived from young animals can attenuate or even reverse aging-related effects [ 195 , 196 , 197 , 198 , 199 , 200 , 201 ]. For example, EVs isolated from the serum of young animals, but not the supernatant devoid of EVs, attenuated several inflammatory markers, such as IL-6 and IL-1β, in old recipient animals [ 195 ].…”

Section: Cell–cell Communication Impairment During Agingmentioning

confidence: 99%

Aging Hallmarks and the Role of Oxidative Stress

et al. 2023

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Aging is a complex biological process accompanied by a progressive decline in the physical function of the organism and an increased risk of age-related chronic diseases such as cardiovascular diseases, cancer, and neurodegenerative diseases. Studies have established that there exist nine hallmarks of the aging process, including (i) telomere shortening, (ii) genomic instability, (iii) epigenetic modifications, (iv) mitochondrial dysfunction, (v) loss of proteostasis, (vi) dysregulated nutrient sensing, (vii) stem cell exhaustion, (viii) cellular senescence, and (ix) altered cellular communication. All these alterations have been linked to sustained systemic inflammation, and these mechanisms contribute to the aging process in timing not clearly determined yet. Nevertheless, mitochondrial dysfunction is one of the most important mechanisms contributing to the aging process. Mitochondria is the primary endogenous source of reactive oxygen species (ROS). During the aging process, there is a decline in ATP production and elevated ROS production together with a decline in the antioxidant defense. Elevated ROS levels can cause oxidative stress and severe damage to the cell, organelle membranes, DNA, lipids, and proteins. This damage contributes to the aging phenotype. In this review, we summarize recent advances in the mechanisms of aging with an emphasis on mitochondrial dysfunction and ROS production.

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Section: Cell–cell Communication Impairment During Agingmentioning

confidence: 99%

Aging Hallmarks and the Role of Oxidative Stress

et al. 2023

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“…It has been shown that miRNAs can be transferred to cancer cells and regulate cellular processes and signaling pathways ( Turchinovich et al, 2011 ; Ramachandran and Palanisamy, 2012 ; Turchinovich and Burwinkel, 2012 ; Turchinovich et al, 2013 ; Chevillet et al, 2014 ; Turchinovich et al, 2015 ; Anfossi et al, 2018 ; Sun et al, 2018 ; Reshke et al, 2020 ). We have found seven miRNAs that are highly stable under normal conditions, which may dysregulate in mutated hematopoietic cells with age ( Coombs et al, 2017 ; Jamieson, 2017 ; Fabre et al, 2022 ; Jeon et al, 2022 ). In addition, this panel of seven miRNA may have use in surgical treatment response.…”

Section: Discussionmentioning

confidence: 99%

A panel of blood-derived miRNAs with a stable expression pattern as a potential pan-cancer detection signature

Sabbaghian

Mussack

Kirchner

et al. 2022

Front. Mol. Biosci.

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Introduction: MicroRNAs have a significant role in the regulation of the transcriptome. Several miRNAs have been proposed as potential biomarkers in different malignancies. However, contradictory results have been reported on the capability of miRNA biomarkers in cancer detection. The human biological clock involves molecular mechanisms that regulate several genes over time. Therefore, the sampling time becomes one of the significant factors in gene expression studies.Method: In the present study, we have tried to find miRNAs with minimum fluctuation in expression levels at different time points that could be more accurate candidates as diagnostic biomarkers. The small RNA-seq raw data of ten healthy individuals across nine-time points were analyzed to identify miRNAs with stable expression.Results: We have found five oscillation patterns. The stable miRNAs were investigated in 779 small-RNA-seq datasets of eleven cancer types. All miRNAs with the highest differential expression were selected for further analysis. The selected miRNAs were explored for functional pathways. The predominantly enriched pathways were miRNA in cancer and the P53-signaling pathway. Finally, we have found seven miRNAs, including miR-142-3p, miR-199a-5p, miR-223-5p, let-7d-5p, miR-148b-3p, miR-340-5p, and miR-421. These miRNAs showed minimum fluctuation in healthy blood and were dysregulated in the blood of eleven cancer types. Conclusion: We have found a signature of seven stable miRNAs which dysregulate in several cancer types and may serve as potential pan-cancer biomarkers.

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“…An important support for this hypothesis comes from experiments in which aged mouse blood is transferred to young animals, which results in features of accelerated ageing. Interestingly, previous treatment of the old donors with senolytic agents reduced “inflamm-ageing” after blood exchange, and the old blood lost its pro-ageing activity [ 11 ]. In humans, senolytic treatments also reduce the “inflamm-ageing” of patients suffering from lung fibrosis [ 12 ] or chronic kidney disease [ 13 ].…”

Section: Mitochondria As Inflammation Triggersmentioning

confidence: 99%

Targeting Mitochondria to Control Ageing and Senescence

Protasoni

Serrano

2023

Pharmaceutics

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Ageing is accompanied by a progressive impairment of cellular function and a systemic deterioration of tissues and organs, resulting in increased vulnerability to multiple diseases. Here, we review the interplay between two hallmarks of ageing, namely, mitochondrial dysfunction and cellular senescence. The targeting of specific mitochondrial features in senescent cells has the potential of delaying or even reverting the ageing process. A deeper and more comprehensive understanding of mitochondrial biology in senescent cells is necessary to effectively face this challenge. Here, we discuss the main alterations in mitochondrial functions and structure in both ageing and cellular senescence, highlighting the differences and similarities between the two processes. Moreover, we describe the treatments available to target these pathways and speculate on possible future directions of anti-ageing and anti-senescence therapies targeting mitochondria.

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Systemic induction of senescence in young mice after single heterochronic blood exchange

Cited by 54 publications

References 45 publications

Aging Hallmarks and the Role of Oxidative Stress

Aging Hallmarks and the Role of Oxidative Stress

A panel of blood-derived miRNAs with a stable expression pattern as a potential pan-cancer detection signature

Targeting Mitochondria to Control Ageing and Senescence

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