Mitochondrial dysfunction as part of an inflammatory intermediate phenotype that drives premature ageing

Stenvinkel, Peter

doi:10.1111/joim.13243

Cited by 7 publications

(3 citation statements)

References 19 publications

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“…A progressive loss of physical functions ahead of time is called premature aging, which is often associated with inflammation, oxidative stress, and immune dysfunction. Mitochondrial dysfunction seems to promote premature aging associated with a reduced life span [14,15]. Short telomere syndromes are accelerated aging syndromes affecting primarily organs with increased cell turnover such as bone marrow, skin, lungs, and gastrointestinal tract.…”

Section: Biology Of Agingmentioning

confidence: 99%

Is Myelodysplasia a Consequence of Normal Aging?

2021

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Purpose of Review To review available data on the relationship of MDS and aging and to address the question if biological changes of (premature) aging are a prerequisite for the development of MDS. Recent Findings Whereas the association of MDS with advanced age and some common biologic features of aging and MDS are well established, additional evidence for both, especially on the role of stem cells, the stem cell niche, and inflammation, has been recently described. Summary Biologically, many but not all drivers of aging also play a role in the development and propagation of MDS and vice versa. As a consequence, aging contributes to the development of MDS which can be seen as an interplay of clonal disease and normal and premature aging. The impact of aging may be different in specific MDS subtypes and risk groups.

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Section: Biology Of Agingmentioning

confidence: 99%

Is Myelodysplasia a Consequence of Normal Aging?

2021

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“…Mitochondrial dysfunction plays a crucial role in the development of MIRI [42]. Numerous cardioprotective measures focus on mitochondria to reduce oxidative stress, inflammatory responses, and alleviate apoptosis [43][44][45]. Both Ta-IIA and As-IV have demonstrated protective effects in MIRI by reducing cardiomyocyte apoptosis [25,46], oxidative stress [25,47], and inflammation [27,48].…”

Section: Discussionmentioning

confidence: 99%

The combination of Tanshinone IIA and Astragaloside IV attenuates myocardial ischemia–reperfusion injury by inhibiting the STING pathway

Zhai,

Chen,

Wang

et al. 2024

Chin Med

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Background Astragaloside IV (As-IV) and Tanshinone IIA (Ta-IIA) are the main ingredients of traditional Chinese medicinal Astragalus membranaceus (Fisch.) Bunge and Salvia miltiorrhiza Bunge, respectively, both of which have been employed in the treatment of cardiovascular diseases. Nevertheless, the efficacy of the combination (Co) of Ta-IIA and As-IV for cardiovascular diseases remain unclear and warrant further investigation. This study aimed to investigate the efficacy and the underlying molecular mechanism of Co in treating myocardial ischemia–reperfusion injury (MIRI). Methods In order to assess the efficacy of Co, an in vivo MIRI mouse model was created by temporarily blocking the coronary arteries for 30 min and then releasing the blockage. Parameters such as blood myocardial enzymes, infarct size, and ventricular function were measured. Additionally, in vitro experiments were conducted using HL1 cells in both hypoxia-reoxygenation model and oxidative stress models. The apoptosis rate, expression levels of apoptosis-related proteins, oxidative stress indexes, and release of inflammatory factors were detected. Furthermore, molecular docking was applied to examine the binding properties of Ta-IIA and As-IV to STING, and western blotting was performed to analyze protein expression of the STING pathway. Additionally, the protective effect of Ta-IIA, As-IV and Co via inhibiting STING was further confirmed in models of knockdown STING by siRNA and adding STING agonist. Results Both in vitro and in vivo data demonstrated that, compared to Ta-IIA or As-IV alone, the Co exhibited superior efficacy in reducing the area of myocardial infarction, lowering myocardial enzyme levels, and promoting the recovery of myocardial contractility. Furthermore, the Co showed more potent anti-apoptosis, antioxidant, and anti-inflammation effects. Additionally, the Co enhanced the inhibitory effects of Ta-IIA and As-IV on STING phosphorylation and the activation of STING signaling pathway. However, the administration of a STING agonist attenuated the protective effects of the Co, Ta-IIA, and As-IV by compromising their anti-apoptotic, antioxidant, and anti-inflammatory effects in MIRI. Conclusion Compared to the individual administration of Ta-IIA or As-IV, the combined treatment demonstrated more potent ability in inhibiting apoptosis, oxidative stress, inflammation, and the STING signaling pathway in the context of MIRI, indicating a more powerful protective effect against MIRI. Graphical Abstract

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“…Defective mitochondria in immune cells can impair their ability to mount an effective immune response, leading to increased susceptibility to infections, impaired wound healing, and chronic inflammation. Mitochondrial dysfunction also drives premature aging (Peter, 2021 ). The release of mtDNA, ROS, ATP, and mitochondrial proteins in the cytosol, as well as the release of mitochondria or their fragments in tissue/bloodstream, may act as potent immunomodulators (Caicedo et al, 2021 ; Morganti & Ito, 2021 ).…”

Section: The Organ‐specific Profile Of Mitochondrial Dysfunction and ...mentioning

confidence: 99%

Interactions between mitochondrial dysfunction and other hallmarks of aging: Paving a path toward interventions that promote healthy old age

Berliocchi

et al. 2023

Aging Cell

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Current research on human aging has largely been guided by the milestone paper “hallmarks of aging,” which were first proposed in the seminal 2013 paper by Lopez‐Otin et al. Most studies have focused on one aging hallmark at a time, asking whether the underlying molecular perturbations are sufficient to drive the aging process and its associated phenotypes. More recently, researchers have begun to investigate whether aging phenotypes are driven by concurrent perturbations in molecular pathways linked to not one but to multiple hallmarks of aging and whether they present different patterns in organs and systems over time. Indeed, preliminary results suggest that more complex interactions between aging hallmarks must be considered and addressed, if we are to develop interventions that successfully promote healthy aging and/or delay aging‐associated dysfunction and diseases. Here, we summarize some of the latest work and views on the interplay between hallmarks of aging, with a specific focus on mitochondrial dysfunction. Indeed, this represents a significant example of the complex crosstalk between hallmarks of aging and of the effects that an intervention targeted to a specific hallmark may have on the others. A better knowledge of these interconnections, of their cause‐effect relationships, of their spatial and temporal sequence, will be very beneficial for the whole aging research field and for the identification of effective interventions in promoting healthy old age.

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Mitochondrial dysfunction as part of an inflammatory intermediate phenotype that drives premature ageing

Abstract: Click here to view the Original article by F.Fazzini et al.

Cited by 7 publications

References 19 publications

Is Myelodysplasia a Consequence of Normal Aging?

Is Myelodysplasia a Consequence of Normal Aging?

The combination of Tanshinone IIA and Astragaloside IV attenuates myocardial ischemia–reperfusion injury by inhibiting the STING pathway

Interactions between mitochondrial dysfunction and other hallmarks of aging: Paving a path toward interventions that promote healthy old age

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