Age-Related Lysosomal Dysfunctions

Guerrero‐Navarro, Lena; Jansen-Duerr, Pidder; Cavinato, Maria

doi:10.3390/cells11121977

Cited by 12 publications

(6 citation statements)

References 145 publications

(194 reference statements)

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“…Cellular redistribution of lysosomes has been previously associated with a secretory phenotype related to senescence 41 – 43 . Several features induced in microgravity, such as alterations in tubulin structure and acetylation, chromatin condensation and repression of cell proliferation, are additional markers of cellular senescence 44 – 46 .…”

Section: Discussionmentioning

confidence: 99%

Microgravity triggers ferroptosis and accelerates senescence in the MG-63 cell model of osteoblastic cells

Garbacki,

Willems,

Neutelings

et al. 2023

npj Microgravity

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In space, cells sustain strong modifications of their mechanical environment. Mechanosensitive molecules at the cell membrane regulate mechanotransduction pathways that induce adaptive responses through the regulation of gene expression, post-translational modifications, protein interactions or intracellular trafficking, among others. In the current study, human osteoblastic cells were cultured on the ISS in microgravity and at 1 g in a centrifuge, as onboard controls. RNAseq analyses showed that microgravity inhibits cell proliferation and DNA repair, stimulates inflammatory pathways and induces ferroptosis and senescence, two pathways related to ageing. Morphological hallmarks of senescence, such as reduced nuclear size and changes in chromatin architecture, proliferation marker distribution, tubulin acetylation and lysosomal transport were identified by immunofluorescence microscopy, reinforcing the hypothesis of induction of cell senescence in microgravity during space flight. These processes could be attributed, at least in part, to the regulation of YAP1 and its downstream effectors NUPR1 and CKAP2L.

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Section: Discussionmentioning

confidence: 99%

Microgravity triggers ferroptosis and accelerates senescence in the MG-63 cell model of osteoblastic cells

Garbacki,

Willems,

Neutelings

et al. 2023

npj Microgravity

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“…Senescent cells show changes in mitochondrial morphology, such as increased mitochondrial mass and size [ 19 , 20 ]. Specifically, age-related lysosomal dysfunction prevents lysosomes from fusing with autophagosomes, limiting the efficient clearance of defective mitochondria via mitophagy and leading to the accumulation of defective mitochondria with aberrant and large morphology [ 21 , 22 ]. The causal role of senescence on mitochondrial morphology is corroborated by the finding that both senescent and H 2 O 2 -induced senescent cells express low levels of FIS1, resulting in an imbalance in mitochondrial fusion–fission [ 23 ] ( Figure 1 B and Table 1 ).…”

Section: Mitochondrial Alterations During the Process Of Senescence A...mentioning

confidence: 99%

Targeting Mitochondrial Oxidative Stress as a Strategy to Treat Aging and Age-Related Diseases

Lee

Kuk

et al. 2023

Antioxidants

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Mitochondria are one of the organelles undergoing rapid alteration during the senescence process. Senescent cells show an increase in mitochondrial size, which is attributed to the accumulation of defective mitochondria, which causes mitochondrial oxidative stress. Defective mitochondria are also targets of mitochondrial oxidative stress, and the vicious cycle between defective mitochondria and mitochondrial oxidative stress contributes to the onset and development of aging and age-related diseases. Based on the findings, strategies to reduce mitochondrial oxidative stress have been suggested for the effective treatment of aging and age-related diseases. In this article, we discuss mitochondrial alterations and the consequent increase in mitochondrial oxidative stress. Then, the causal role of mitochondrial oxidative stress on aging is investigated by examining how aging and age-related diseases are exacerbated by induced stress. Furthermore, we assess the importance of targeting mitochondrial oxidative stress for the regulation of aging and suggest different therapeutic strategies to reduce mitochondrial oxidative stress. Therefore, this review will not only shed light on a new perspective on the role of mitochondrial oxidative stress in aging but also provide effective therapeutic strategies for the treatment of aging and age-related diseases through the regulation of mitochondrial oxidative stress.

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“…Regardless of the molecules being degraded, the internal lysosomal contents require strict regulation to prevent spillage into the cytosol. For reasons still unknown, lysosomal permeability increases in frequency with age ( Guerrero-Navarro et al, 2022 ).…”

Section: Primary Hallmarks Of Aging: Genomic Instability Telomere Att...mentioning

confidence: 99%

Aging, longevity, and the role of environmental stressors: a focus on wildfire smoke and air quality

Scieszka,

Bolt,

McCormick

et al. 2023

Front. Toxicol.

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Aging is a complex biological process involving multiple interacting mechanisms and is being increasingly linked to environmental exposures such as wildfire smoke. In this review, we detail the hallmarks of aging, emphasizing the role of telomere attrition, cellular senescence, epigenetic alterations, proteostasis, genomic instability, and mitochondrial dysfunction, while also exploring integrative hallmarks - altered intercellular communication and stem cell exhaustion. Within each hallmark of aging, our review explores how environmental disasters like wildfires, and their resultant inhaled toxicants, interact with these aging mechanisms. The intersection between aging and environmental exposures, especially high-concentration insults from wildfires, remains under-studied. Preliminary evidence, from our group and others, suggests that inhaled wildfire smoke can accelerate markers of neurological aging and reduce learning capabilities. This is likely mediated by the augmentation of circulatory factors that compromise vascular and blood-brain barrier integrity, induce chronic neuroinflammation, and promote age-associated proteinopathy-related outcomes. Moreover, wildfire smoke may induce a reduced metabolic, senescent cellular phenotype. Future interventions could potentially leverage combined anti-inflammatory and NAD + boosting compounds to counter these effects. This review underscores the critical need to study the intricate interplay between environmental factors and the biological mechanisms of aging to pave the way for effective interventions.

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Age-Related Lysosomal Dysfunctions

Cited by 12 publications

References 145 publications

Microgravity triggers ferroptosis and accelerates senescence in the MG-63 cell model of osteoblastic cells

Microgravity triggers ferroptosis and accelerates senescence in the MG-63 cell model of osteoblastic cells

Targeting Mitochondrial Oxidative Stress as a Strategy to Treat Aging and Age-Related Diseases

Aging, longevity, and the role of environmental stressors: a focus on wildfire smoke and air quality

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