Turning the Oxygen Dial: Balancing the Highs and Lows

Baik, Alan H.; Jain, Isha H.

doi:10.1016/j.tcb.2020.04.005

Cited by 48 publications

(32 citation statements)

References 221 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Oxygen concentrations vary strongly depending on the tissue and species 69 , so physiological levels for relevant cell types is an important consideration when studying senescence. Several recent articles review the role of oxygen in diverse biological phenomena, including senescence 63,[69][70][71] .…”

Section: Metabolic Drivers Of Senescencementioning

confidence: 99%

The metabolic roots of senescence: mechanisms and opportunities for intervention

2021

View full text Add to dashboard Cite

Cellular senescence entails a permanent proliferative arrest, coupled to multiple phenotypic changes. Among these changes is the release of numerous biologically active molecules collectively known as the senescence-associated secretory phenotype, or SASP. A growing body of literature indicates that both senescence and the SASP are sensitive to cellular and organismal metabolic states, which in turn can drive phenotypes associated with metabolic dysfunction. Here, we review the current literature linking senescence and metabolism, with an eye toward findings at the cellular level, including both metabolic inducers of senescence and alterations in cellular metabolism associated with senescence. Additionally, we consider how interventions that target either metabolism or senescent cells might influence each other and mitigate some of the pro-aging effects of cellular senescence. We conclude that the most effective interventions will likely break a degenerative feedback cycle by which cellular senescence promotes metabolic diseases, which in turn promote senescence.

show abstract

Section: Metabolic Drivers Of Senescencementioning

confidence: 99%

The metabolic roots of senescence: mechanisms and opportunities for intervention

2021

View full text Add to dashboard Cite

show abstract

“…In former times interpreted as principally pathological, for instance upon cardiac arrest, hypoxia is increasingly recognized as physiological driving force of early neurodevelopment including angiogenesis, hematopoiesis, and tissue regeneration. Known cellular environments experiencing hypoxia include developing embryos, stem cell niches, the renal papilla, inflammatory tissue, or the inner mass of tumours [1][2][3][4][5][6][7][8][9][10]. A specific transcriptional programme, induced by hypoxia, allows cells to adapt to lower oxygen levels and/or to limited metabolic support [11].…”

Section: Introductionmentioning

confidence: 99%

Hippocampal neurons respond to brain activity with functional hypoxia

et al. 2021

View full text Add to dashboard Cite

Physical activity and cognitive challenge are established non-invasive methods to induce comprehensive brain activation and thereby improve global brain function including mood and emotional well-being in healthy subjects and in patients. However, the mechanisms underlying this experimental and clinical observation and broadly exploited therapeutic tool are still widely obscure. Here we show in the behaving brain that physiological (endogenous) hypoxia is likely a respective lead mechanism, regulating hippocampal plasticity via adaptive gene expression. A refined transgenic approach in mice, utilizing the oxygen-dependent degradation (ODD) domain of HIF-1α fused to CreERT2 recombinase, allows us to demonstrate hypoxic cells in the performing brain under normoxia and motor-cognitive challenge, and spatially map them by light-sheet microscopy, all in comparison to inspiratory hypoxia as strong positive control. We report that a complex motor-cognitive challenge causes hypoxia across essentially all brain areas, with hypoxic neurons particularly abundant in the hippocampus. These data suggest an intriguing model of neuroplasticity, in which a specific task-associated neuronal activity triggers mild hypoxia as a local neuron-specific as well as a brain-wide response, comprising indirectly activated neurons and non-neuronal cells.

show abstract

“…In hypoxic environments, HIFα subunits are not hydroxylated, which mediates protein stabilization. HIFα subunits heterodimerize with HIFβ subunits to form a nuclear heterodimer, which drives target gene transcription by binding to the hypoxia response element (HRE) (Baik and Jain, 2020).…”

Section: Hif Pathwaymentioning

confidence: 99%

Immune and Metabolic Alterations in Liver Fibrosis: A Disruption of Oxygen Homeostasis?

Zhang

Wang

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

According to the WHO, “cirrhosis of the liver” was the 11th leading cause of death globally in 2019. Many kinds of liver diseases can develop into liver cirrhosis, and liver fibrosis is the main pathological presentation of different aetiologies, including toxic damage, viral infection, and metabolic and genetic diseases. It is characterized by excessive synthesis and decreased decomposition of extracellular matrix (ECM). Hepatocyte cell death, hepatic stellate cell (HSC) activation, and inflammation are crucial incidences of liver fibrosis. The process of fibrosis is also closely related to metabolic and immune disorders, which are usually induced by the destruction of oxygen homeostasis, including mitochondrial dysfunction, oxidative stress, and hypoxia pathway activation. Mitochondria are important organelles in energy generation and metabolism. Hypoxia-inducible factors (HIFs) are key factors activated when hypoxia occurs. Both are considered essential factors of liver fibrosis. In this review, the authors highlight the impact of oxygen imbalance on metabolism and immunity in liver fibrosis as well as potential novel targets for antifibrotic therapies.

show abstract

Turning the Oxygen Dial: Balancing the Highs and Lows

Cited by 48 publications

References 221 publications

The metabolic roots of senescence: mechanisms and opportunities for intervention

The metabolic roots of senescence: mechanisms and opportunities for intervention

Hippocampal neurons respond to brain activity with functional hypoxia

Immune and Metabolic Alterations in Liver Fibrosis: A Disruption of Oxygen Homeostasis?

Contact Info

Product

Resources

About