Volume 4, Issue 2

Mitochondrial dysfunction and cell senescence — skin deep into mammalian aging

Joao F. Passos, Thomas von Zglinicki,

https://doi.org/10.18632/aging.100432 pp 74—75

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Passos JF, von Zglinicki T, . Mitochondrial dysfunction and cell senescence — skin deep into mammalian aging. . 4:74-75. https://doi.org/10.18632/aging.100432

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Telomeres and longevity

Pat Monaghan,

https://doi.org/10.18632/aging.100437 pp 76—77

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Genome integrity, stem cells and hyaluronan

Zbigniew Darzynkiewicz, Endre A. Balazs,

https://doi.org/10.18632/aging.100438 pp 78—88

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Darzynkiewicz Z, Balazs EA, . Genome integrity, stem cells and hyaluronan. . 4:78-88. https://doi.org/10.18632/aging.100438

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                TY  - JOUR
                AU  - Darzynkiewicz, Zbigniew 
                AU  - Balazs, Endre A. 
                TI  - Genome integrity, stem cells and hyaluronan
                JO  - 
                JA  - 
                VL  - 4
                IS  - 2
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100438
                DO  - 10.18632/aging.100438
                SP  - 78
                EP  - 88
                PY  - 
                AB  - Faithful preservation of genome integrity is the critical mission of stem cells as well as of germ cells. Reviewed are the following mechanisms involved in protecting DNA in these cells: (a) The efflux machinery that can pump out variety of genotoxins in ATP-dependent manner; (b) the mechanisms maintaining minimal metabolic activity which reduces generation of reactive oxidants, by-products of aerobic respiration; (c) the role of hypoxic niche of stem cells providing a gradient of variable oxygen tension; (d) (e) the presence of hyaluronan (HA) and HA receptors on stem cells and in the niche; (f) the role of HA in protecting DNA from oxidative damage; (g) the specific function of HA in protecting DNA in stem cells; (h) the interactions of HA with sperm cells and oocytes that also may shield their DNA from oxidative damage, and (e) mechanisms by which HA exerts the anti-oxidant activity. While HA has multitude of functions its anti-oxidant capabilities are often overlooked but may be of significance in preservation of integrity of stem and germ cells genome.
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Interaction between the Cockayne syndrome B and p53 proteins: implications for aging

Mattia Frontini, Luca Proietti-De-Santis,

https://doi.org/10.18632/aging.100439 pp 89—97

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Frontini M, Proietti-De-Santis L, . Interaction between the Cockayne syndrome B and p53 proteins: implications for aging. . 4:89-97. https://doi.org/10.18632/aging.100439

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                TY  - JOUR
                AU  - Frontini, Mattia 
                AU  - Proietti-De-Santis, Luca 
                TI  - Interaction between the Cockayne syndrome B and p53 proteins: implications for aging
                JO  - 
                JA  - 
                VL  - 4
                IS  - 2
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100439
                DO  - 10.18632/aging.100439
                SP  - 89
                EP  - 97
                PY  - 
                AB  - The CSB protein plays a role in the transcription coupled repair (TCR) branch of the nucleotide excision repair pathway. CSB is very often found mutated in Cockayne syndrome, a segmental progeroid genetic disease characterized by organ degeneration and growth failure. The tumor suppressor p53 plays a pivotal role in triggering senescence and apoptosis and suppressing tumorigenesis. Although p53 is very important to avoid cancer, its excessive activity can be detrimental for the lifespan of the organism. This is why a network of positive and negative feedback loops, which most likely evolved to fine-tune the activity of this tumor suppressor, modulate its induction and activation. Accordingly, an unbalanced p53 activity gives rise to premature aging or cancer. The physical interaction between CSB and p53 proteins has been known for more than a decade but, despite several hypotheses, nobody has been able to show the functional consequences of this interaction. In this review we resume recent advances towards a more comprehensive understanding of the critical role of this interaction in modulating p53's levels and activity, therefore helping the system find a reasonable equilibrium between the beneficial and the detrimental effects of its activity. This crosstalk re-establishes the physiological balance towards cell proliferation and survival instead of towards cell death, after stressors of a broad nature. Accordingly, cells bearing mutations in the csb gene are unable to re-establish this physiological balance and to properly respond to some stress stimuli and undergo massive apoptosis.
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Inflammatory cause of metabolic syndrome via brain stress and NF-κB

Dongsheng Cai, Tiewen Liu,

https://doi.org/10.18632/aging.100431 pp 98—115

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Cai D, Liu T, . Inflammatory cause of metabolic syndrome via brain stress and NF-κB. . 4:98-115. https://doi.org/10.18632/aging.100431

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                TY  - JOUR
                AU  - Cai, Dongsheng 
                AU  - Liu, Tiewen 
                TI  - Inflammatory cause of metabolic syndrome via brain stress and NF-κB
                JO  - 
                JA  - 
                VL  - 4
                IS  - 2
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100431
                DO  - 10.18632/aging.100431
                SP  - 98
                EP  - 115
                PY  - 
                AB  - Metabolic syndrome, a network of medical disorders that greatly increase the risk for developing metabolic and cardiovascular diseases, has reached epidemic levels in many areas of today's world. Despite this alarming medicare situation, scientific understandings on the root mechanisms of metabolic syndrome are still limited, and such insufficient knowledge contributes to the relative lack of effective treatments or preventions for related diseases. Recent interdisciplinary studies from neuroendocrinology and neuroimmunology fields have revealed that overnutrition can trigger intracellular stresses to cause inflammatory changes mediated by molecules that control innate immunity. This type of nutrition-related molecular inflammation in the central nervous system, particularly in the hypothalamus, can form a common pathogenic basis for the induction of various metabolic syndrome components such as obesity, insulin resistance, and hypertension. Proinflammatory NF-κB pathway has been revealed as a key molecular system for pathologic induction of brain inflammation, which translates overnutrition and resulting intracellular stresses into central neuroendocrine and neural dysregulations of energy, glucose, and cardiovascular homeostasis, collectively leading to metabolic syndrome. This article reviews recent research advances in the neural mechanisms of metabolic syndrome and related diseases from the perspective of pathogenic induction by intracellular stresses and NF-κB pathway of the brain.
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SOD2 deficiency promotes aging phenotypes in mouse skin

Urbain Weyemi, Palak R. Parekh, Christophe E. Redon, William M. Bonner,

https://doi.org/10.18632/aging.100433 pp 116—118

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Weyemi U, Parekh PR, Redon CE, Bonner WM, . SOD2 deficiency promotes aging phenotypes in mouse skin. . 4:116-118. https://doi.org/10.18632/aging.100433

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Automated image analysis of nuclear shape: What can we learn from a prematurely aged cell?

Meghan K. Driscoll, Jason L. Albanese, Zheng-Mei Xiong, Mitch Mailman, Wolfgang Losert, Kan Cao,

https://doi.org/10.18632/aging.100434 pp 119—132

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Driscoll MK, Albanese JL, Xiong Z, Mailman M, Losert W, Cao K, . Automated image analysis of nuclear shape: What can we learn from a prematurely aged cell?. . 4:119-132. https://doi.org/10.18632/aging.100434

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                TY  - JOUR
                AU  - Driscoll, Meghan K. 
                AU  - Albanese, Jason L. 
                AU  - Xiong, Zheng-Mei 
                AU  - Mailman, Mitch 
                AU  - Losert, Wolfgang 
                AU  - Cao, Kan 
                TI  - Automated image analysis of nuclear shape: What can we learn from a prematurely aged cell?
                JO  - 
                JA  - 
                VL  - 4
                IS  - 2
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100434
                DO  - 10.18632/aging.100434
                SP  - 119
                EP  - 132
                PY  - 
                AB  - The premature aging disorder, Hutchinson-Gilford progeria syndrome (HGPS), is caused by mutant lamin A, which affects the nuclear scaffolding. The phenotypic hallmark of HGPS is nuclear blebbing. Interestingly, similar nuclear blebbing has also been observed in aged cells from healthy individuals. Recent work has shown that treatment with rapamycin, an inhibitor of the mTOR pathway, reduced nuclear blebbing in HGPS fibroblasts. However, the extent of blebbing varies considerably within each cell population, which makes manual blind counting challenging and subjective. Here, we show a novel, automated and high throughput nuclear shape analysis that quantitatively measures curvature, area, perimeter, eccentricity and additional metrics of nuclear morphology for large populations of cells. We examined HGPS fibroblast cells treated with rapamycin and RAD001 (an analog to rapamycin). Our analysis shows that treatment with RAD001 and rapamycin reduces nuclear blebbing, consistent with blind counting controls. In addition, we find that rapamycin treatment reduces the area of the nucleus, but leaves the eccentricity unchanged. Our nuclear shape analysis provides an unbiased, multidimensional “fingerprint” for a population of cells, which can be used to quantify treatment efficacy and analyze cellular aging.
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Disruption of MEF2C signaling and loss of sarcomeric and mitochondrial integrity in cancer-induced skeletal muscle wasting

Angie M. Y. Shum, Theodore Mahendradatta, Ryland J. Taylor, Arran B. Painter, Melissa M. Moore, Maria Tsoli, Timothy C. Tan, Stephen J. Clarke, Graham R. Robertson, Patsie Polly,

https://doi.org/10.18632/aging.100436 pp 133—143

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Shum AMY, Mahendradatta T, Taylor RJ, Painter AB, Moore MM, Tsoli M, Tan TC, Clarke SJ, Robertson GR, Polly P, . Disruption of MEF2C signaling and loss of sarcomeric and mitochondrial integrity in cancer-induced skeletal muscle wasting. . 4:133-143. https://doi.org/10.18632/aging.100436

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                TY  - JOUR
                AU  - Shum, Angie M. Y. 
                AU  - Mahendradatta, Theodore 
                AU  - Taylor, Ryland J. 
                AU  - Painter, Arran B. 
                AU  - Moore, Melissa M. 
                AU  - Tsoli, Maria 
                AU  - Tan, Timothy C. 
                AU  - Clarke, Stephen J. 
                AU  - Robertson, Graham R. 
                AU  - Polly, Patsie 
                TI  - Disruption of MEF2C signaling and loss of sarcomeric and mitochondrial integrity in cancer-induced skeletal muscle wasting
                JO  - 
                JA  - 
                VL  - 4
                IS  - 2
                PB  - 
                SN  - 
                UR  - https://doi.org/10.18632/aging.100436
                DO  - 10.18632/aging.100436
                SP  - 133
                EP  - 143
                PY  - 
                AB  - Cancer cachexia is a highly debilitating paraneoplastic disease observed in more than 50% of patients with advanced cancers and directly contributes to 20% of cancer deaths. Loss of skeletal muscle is a defining characteristic of patients with cancer cachexia and is associated with poor survival. The present study reveals the involvement of a myogenic transcription factor Myocyte Enhancer Factor (MEF) 2C in cancer-induced skeletal muscle wasting. Increased skeletal muscle mRNA expression of Suppressor of Cytokine Signaling (Socs) 3 and the IL-6 receptor indicative of active IL-6 signaling was seen in skeletal muscle of mice bearing the Colon 26 (C26) carcinoma. Loss of skeletal muscle structural integrity and distorted mitochondria were also observed using electron microscopy. Gene and protein expression of MEF2C was significantly downregulated in skeletal muscle from C26-bearing mice. MEF2C gene targets myozenin and myoglobin as well as myokinase were also altered during cachexia, suggesting dysregulated oxygen transport capacity and ATP regeneration in addition to distorted structural integrity. In addition, reduced expression of calcineurin was observed which suggested a potential pathway of MEF2C dysregulation. Together, these effects may limit sarcomeric contractile ability and also predispose skeletal muscle to structural instability; associated with muscle wasting and fatigue in cachexia.
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Volume 4, Issue 2

Mitochondrial dysfunction and cell senescence — skin deep into mammalian aging

Joao F. Passos, Thomas von Zglinicki,

Editorial

Telomeres and longevity

Pat Monaghan,

Reviews

Genome integrity, stem cells and hyaluronan

Zbigniew Darzynkiewicz, Endre A. Balazs,

Interaction between the Cockayne syndrome B and p53 proteins: implications for aging

Mattia Frontini, Luca Proietti-De-Santis,

Research Perspectives

Inflammatory cause of metabolic syndrome via brain stress and NF-κB

Dongsheng Cai, Tiewen Liu,

SOD2 deficiency promotes aging phenotypes in mouse skin

Urbain Weyemi, Palak R. Parekh, Christophe E. Redon, William M. Bonner,

Research Papers

Automated image analysis of nuclear shape: What can we learn from a prematurely aged cell?

Meghan K. Driscoll, Jason L. Albanese, Zheng-Mei Xiong, Mitch Mailman, Wolfgang Losert, Kan Cao,

Disruption of MEF2C signaling and loss of sarcomeric and mitochondrial integrity in cancer-induced skeletal muscle wasting

Angie M. Y. Shum, Theodore Mahendradatta, Ryland J. Taylor, Arran B. Painter, Melissa M. Moore, Maria Tsoli, Timothy C. Tan, Stephen J. Clarke, Graham R. Robertson, Patsie Polly,

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