Astrocyte Senescence and Metabolic Changes in Response to HIV Antiretroviral Therapy Drugs

Cohen, Justin; D’Agostino, Luca; Wilson, Joel; Tüzer, Ferit; Torres, Claudio

doi:10.3389/fnagi.2017.00281

Cited by 50 publications

(37 citation statements)

References 48 publications

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“…Metabolic profiling of senescent fibroblasts has shown elevated activity of glycolysis that can be explained by mitochondrial dysfunction in aging cells (James et al, 2015 ). Similar effect has been observed in senescent astrocytes where up-regulation of glycolysis corresponded to the degree of mitochondrial overactivation, ROS production, and inflammatory response of astroglia (Cohen et al, 2017 ). Thus, elevated glycolytic flux might be a part of cell protective mechanism to prevent NAD + depletion and to delay cell aging.…”

Section: Mechanisms and Markers Of Cell Senescence: Applications For supporting

confidence: 64%

Designing in vitro Blood-Brain Barrier Models Reproducing Alterations in Brain Aging

Осипова

Komleva

Моргун

et al. 2018

Front. Aging Neurosci.

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Blood-brain barrier (BBB) modeling in vitro is a huge area of research covering study of intercellular communications and development of BBB, establishment of specific properties that provide controlled permeability of the barrier. Current approaches in designing new BBB models include development of new (bio) scaffolds supporting barriergenesis/angiogenesis and BBB integrity; use of methods enabling modulation of BBB permeability; application of modern analytical techniques for screening the transfer of metabolites, bio-macromolecules, selected drug candidates and drug delivery systems; establishment of 3D models; application of microfluidic technologies; reconstruction of microphysiological systems with the barrier constituents. Acceptance of idea that BBB in vitro models should resemble real functional activity of the barrier in different periods of ontogenesis and in different (patho) physiological conditions leads to proposal that establishment of BBB in vitro model with alterations specific for aging brain is one of current challenges in neurosciences and bioengineering. Vascular dysfunction in the aging brain often associates with leaky BBB, alterations in perivascular microenvironment, neuroinflammation, perturbed neuronal and astroglial activity within the neurovascular unit, impairments in neurogenic niches where microvascular scaffold plays a key regulatory role. The review article is focused on aging-related alterations in BBB and current approaches to development of “aging” BBB models in vitro.

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Section: Mechanisms and Markers Of Cell Senescence: Applications For supporting

confidence: 64%

Designing in vitro Blood-Brain Barrier Models Reproducing Alterations in Brain Aging

Осипова

Komleva

Моргун

et al. 2018

Front. Aging Neurosci.

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“…The authors also demonstrated an increase in senescent astrocytes from several rat models of HIV infection, providing in vivo relevance. On the antiretroviral side of HIV‐associated stimuli, HAART drug has been shown to induce premature senescence in human astrocytes, the first study to demonstrate HAART‐mediated senescence of a CNS cell type (Cohen, D'Agostino, Wilson, Tuzer, & Torres, ). These astrocytes showed signs of oxidative stress and mitochondrial dysfunction accompanied by changes in metabolism, indicating that HAART drug‐mediated astrocyte senescence can dramatically affect normal astrocyte physiology.…”

Section: Neurodegenerative Disease and Astrocyte Senescencementioning

confidence: 99%

Astrocyte senescence: Evidence and significance

2019

Self Cite

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Astrocytes participate in numerous aspects of central nervous system (CNS) physiology ranging from ion balance to metabolism, and disruption of their physiological roles can therefore be a contributor to CNS dysfunction and pathology. Cellular senescence, one of the mechanisms of aging, has been proposed as a central component of the age dependency of neurodegenerative disorders. Cumulative evidence supports an integral role of astrocytes in the initiation and progression of neurodegenerative disease and cognitive decline with aging. The loss of astrocyte function or the gain of neuroinflammatory function as a result of cellular senescence could have profound implications for the aging brain and neurodegenerative disorders, and we propose the term “astrosenescence” to describe this phenotype. This review summarizes the current evidence pertaining to astrocyte senescence from early evidence, in vitro characterization and relationship to age‐related neurodegenerative disease. We discuss the significance of targeting senescent astrocytes as a novel approach toward therapies for age‐associated neurodegenerative disease.

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“…In culture, it was also shown that beta-amyloid could trigger cell senescence, suggesting that senescent astrocytes may increase the risk of sporadic AD. In another study related to HIV therapy, it was reported that highly active antiretroviral therapy (HAART) increases biomarkers associated with cell senescence (cell cycle arrest, SA-Beta-Gal activity, p21 expression) in primary cultures of human astrocytes (Cohen et al, 2017). It was suggested that HAART-induced senescent astrocytes may play a role in neurocognitive impairment observed in HIV-infected patients.…”

Section: Natural Killer Cellsmentioning

confidence: 99%

Cellular senescence: Immunosurveillance and future immunotherapy

Burton

Stolzing

2018

Ageing Research Reviews

182

141

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In response to persistent DNA damage, induction into cell senescence promotes an immunogenic program which facilitates immune clearance of these damaged cells. Under physiological conditions, senescent cells can activate both innate and adaptive immune responses, functioning to maintain tissue homeostasis. In addition, emerging findings suggest that programmed induction of cell senescence may be important for regulating reproductive processes, partly facilitated by immune clearance. However, likely owing to ageing of the immune system, a failure to eliminate senescent cells can contribute to their persistence in tissues, leading to the development and progression of age-related diseases. Such immune failure may in part be due to activation of the senescence program in immune cells, leading to their dysfunction. Furthermore, senescent cells under certain biological contexts have been shown to instead promote immune suppression, a response that may reflect differences between an acute verses chronic senescent phenotype. In this review, we provide an overview of the research to date concerning senescence immunosurviellance, including a focused discussion on the mechanisms by which macrophages may recognise senescent cells. Senescence immunotherapy strategies as an alternative to senolytics for the removal of senescent cells will also be discussed.

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Astrocyte Senescence and Metabolic Changes in Response to HIV Antiretroviral Therapy Drugs

Cited by 50 publications

References 48 publications

Designing in vitro Blood-Brain Barrier Models Reproducing Alterations in Brain Aging

Designing in vitro Blood-Brain Barrier Models Reproducing Alterations in Brain Aging

Astrocyte senescence: Evidence and significance

Cellular senescence: Immunosurveillance and future immunotherapy

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