The Experts below are selected from a list of 2979 Experts worldwide ranked by ideXlab platform

Thomas A Rando - One of the best experts on this subject based on the ideXlab platform.

  • rejuvenation of aged Progenitor Cells by exposure to a young systemic environment
    Nature, 2005
    Co-Authors: Irina M. Conboy, Eric R. Girma, Amy J. Wagers, Michael J. Conboy, Irving L Weissman, Thomas A Rando
    Abstract:

    Tissues of the body regenerate well in young individuals, less so in older individuals. To find out if this decline is irreversible, or subject to factors in the circulation, Conboy et al. joined together the circulatory systems of young and old mice, as a ‘parabiotic’ pair. Strikingly, regenerative properties of aged muscle and liver were rejuvenated by the serum from younger animals. At the same time there was a restoration of young ‘molecular signatures’, involving Notch signalling (in muscle) and cEBPa-mediated Cell cycle regulation (in liver). This suggests that stem and Progenitor Cells retain proliferative potential even when old, and that the ‘young’ pattern of molecular signalling can reactivate tissue regeneration. The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in tissue-specific stem Cells1,2,3,4,5. A decline in skeletal muscle stem Cell (satellite Cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle1,6. The decline in Hepatic Progenitor Cell proliferation owing to the formation of a complex involving cEBP-α and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver7. To examine the influence of systemic factors on aged Progenitor Cells from these tissues, we established parabiotic pairings (that is, a shared circulatory system) between young and old mice (heterochronic parabioses), exposing old mice to factors present in young serum. Notably, heterochronic parabiosis restored the activation of Notch signalling as well as the proliferation and regenerative capacity of aged satellite Cells. The exposure of satellite Cells from old mice to young serum enhanced the expression of the Notch ligand (Delta), increased Notch activation, and enhanced proliferation in vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte proliferation and restored the cEBP-α complex to levels seen in young animals. These results suggest that the age-related decline of Progenitor Cell activity can be modulated by systemic factors that change with age.

  • Rejuvenation of aged Progenitor Cells by exposure to a young systemic environment
    Nature, 2005
    Co-Authors: Irina M. Conboy, Eric R. Girma, Irving L. Weismann, Amy J. Wagers, Michael J. Conboy, Thomas A Rando
    Abstract:

    The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in tissue-specific stem Cells. A decline in skeletal muscle stem Cell (satellite Cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle. The decline in Hepatic Progenitor Cell proliferation owing to the formation of a complex involving cEBP-alpha and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver. To examine the influence of systemic factors on aged Progenitor Cells from these tissues, we established parabiotic pairings (that is, a shared circulatory system) between young and old mice (heterochronic parabioses), exposing old mice to factors present in young serum. Notably, heterochronic parabiosis restored the activation of Notch signalling as well as the proliferation and regenerative capacity of aged satellite Cells. The exposure of satellite Cells from old mice to young serum enhanced the expression of the Notch ligand (Delta), increased Notch activation, and enhanced proliferation in vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte proliferation and restored the cEBP-alpha complex to levels seen in young animals. These results suggest that the age-related decline of Progenitor Cell activity can be modulated by systemic factors that change with age.

Amy J. Wagers - One of the best experts on this subject based on the ideXlab platform.

  • rejuvenation of aged Progenitor Cells by exposure to a young systemic environment
    Nature, 2005
    Co-Authors: Irina M. Conboy, Eric R. Girma, Amy J. Wagers, Michael J. Conboy, Irving L Weissman, Thomas A Rando
    Abstract:

    Tissues of the body regenerate well in young individuals, less so in older individuals. To find out if this decline is irreversible, or subject to factors in the circulation, Conboy et al. joined together the circulatory systems of young and old mice, as a ‘parabiotic’ pair. Strikingly, regenerative properties of aged muscle and liver were rejuvenated by the serum from younger animals. At the same time there was a restoration of young ‘molecular signatures’, involving Notch signalling (in muscle) and cEBPa-mediated Cell cycle regulation (in liver). This suggests that stem and Progenitor Cells retain proliferative potential even when old, and that the ‘young’ pattern of molecular signalling can reactivate tissue regeneration. The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in tissue-specific stem Cells1,2,3,4,5. A decline in skeletal muscle stem Cell (satellite Cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle1,6. The decline in Hepatic Progenitor Cell proliferation owing to the formation of a complex involving cEBP-α and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver7. To examine the influence of systemic factors on aged Progenitor Cells from these tissues, we established parabiotic pairings (that is, a shared circulatory system) between young and old mice (heterochronic parabioses), exposing old mice to factors present in young serum. Notably, heterochronic parabiosis restored the activation of Notch signalling as well as the proliferation and regenerative capacity of aged satellite Cells. The exposure of satellite Cells from old mice to young serum enhanced the expression of the Notch ligand (Delta), increased Notch activation, and enhanced proliferation in vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte proliferation and restored the cEBP-α complex to levels seen in young animals. These results suggest that the age-related decline of Progenitor Cell activity can be modulated by systemic factors that change with age.

  • Rejuvenation of aged Progenitor Cells by exposure to a young systemic environment
    Nature, 2005
    Co-Authors: Irina M. Conboy, Eric R. Girma, Irving L. Weismann, Amy J. Wagers, Michael J. Conboy, Thomas A Rando
    Abstract:

    The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in tissue-specific stem Cells. A decline in skeletal muscle stem Cell (satellite Cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle. The decline in Hepatic Progenitor Cell proliferation owing to the formation of a complex involving cEBP-alpha and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver. To examine the influence of systemic factors on aged Progenitor Cells from these tissues, we established parabiotic pairings (that is, a shared circulatory system) between young and old mice (heterochronic parabioses), exposing old mice to factors present in young serum. Notably, heterochronic parabiosis restored the activation of Notch signalling as well as the proliferation and regenerative capacity of aged satellite Cells. The exposure of satellite Cells from old mice to young serum enhanced the expression of the Notch ligand (Delta), increased Notch activation, and enhanced proliferation in vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte proliferation and restored the cEBP-alpha complex to levels seen in young animals. These results suggest that the age-related decline of Progenitor Cell activity can be modulated by systemic factors that change with age.

John K Olynyk - One of the best experts on this subject based on the ideXlab platform.

  • interferon γ exacerbates liver damage the Hepatic Progenitor Cell response and fibrosis in a mouse model of chronic liver injury
    Journal of Hepatology, 2007
    Co-Authors: Belinda Knight, George C T Yeoh, John K Olynyk
    Abstract:

    Background/Aims Several previous studies have suggested that interferon gamma (IFNγ) may play a key role during Hepatic Progenitor Cell (HPC) mediated liver regeneration. However to date, no studies have directly tested the ability of IFNγ to mediate the HPC response in an in vivo model. Methods/Results Administration of IFNγ to mice receiving a choline deficient, ethionine (CDE) supplemented diet to induce chronic injury resulted in an augmented HPC response. This was accompanied by increased inflammation, altered cytokine expression and Hepatic fibrosis. Serum alanine aminotransferase activity, hepatocyte apoptosis and Bak staining were significantly increased in IFNγ-treated, CDE-fed mice, demonstrating that liver damage was exacerbated in these animals. Administration of IFNγ to control diet fed mice did not induce liver damage, however it did stimulate Hepatic inflammation. Conclusions Our results suggest that IFNγ increases the HPC response to injury by stimulating Hepatic inflammation and aggravating liver damage. This is accompanied by an increase in Hepatic fibrogenesis, supporting previous reports which suggest that the HPC response may drive fibrogenesis during chronic liver injury.

  • attenuated liver Progenitor oval Cell and fibrogenic responses to the choline deficient ethionine supplemented diet in the balb c inbred strain of mice
    Journal of Hepatology, 2007
    Co-Authors: Belinda Knight, John K Olynyk, Barbara Akhurst, Vance B Matthews, Richard G Ruddell, Grant A Ramm, Lawrence J Abraham, George C T Yeoh
    Abstract:

    Background/Aims Liver regeneration following chronic injury is associated with inflammation, the proliferation of liver Progenitor (oval) Cells and fibrosis. Previous studies identified interferon-gamma as a key mediator of oval Cell proliferation. Interferon-γ is known to regulate Th1 Cell activities during immune challenge. Therefore, we hypothesised that Progenitor Cell-mediated regeneration is associated with a Th1 immune response. Methods C57Bl/6 (normal Th1 response) and BALB/c mice (deficient in Th1 signalling) were placed on a carcinogenic diet to induce liver injury, Progenitor Cell proliferation and fibrosis. Results Serum transaminases and mortality were elevated in BALB/c mice fed the diet. Proliferation of liver Progenitor Cells was significantly attenuated in BALB/c animals. The pattern of cytokine expression and inflammation differed between strains. Liver fibrosis and Hepatic stellate Cell activation were significantly inhibited in BALB/c mice compared to C57Bl/6. In addition, interferon-γ knockout mice also showed reduced fibrosis compared to wild type. These findings are in contrast to published results, in which interferon-gamma is shown to be anti-fibrogenic. Conclusions Our data demonstrate that the Hepatic Progenitor Cell response to a CDE diet is inhibited in mice lacking Th1 immune signalling and further show that this inhibition is associated with reduced liver fibrosis.

Irina M. Conboy - One of the best experts on this subject based on the ideXlab platform.

  • rejuvenation of aged Progenitor Cells by exposure to a young systemic environment
    Nature, 2005
    Co-Authors: Irina M. Conboy, Eric R. Girma, Amy J. Wagers, Michael J. Conboy, Irving L Weissman, Thomas A Rando
    Abstract:

    Tissues of the body regenerate well in young individuals, less so in older individuals. To find out if this decline is irreversible, or subject to factors in the circulation, Conboy et al. joined together the circulatory systems of young and old mice, as a ‘parabiotic’ pair. Strikingly, regenerative properties of aged muscle and liver were rejuvenated by the serum from younger animals. At the same time there was a restoration of young ‘molecular signatures’, involving Notch signalling (in muscle) and cEBPa-mediated Cell cycle regulation (in liver). This suggests that stem and Progenitor Cells retain proliferative potential even when old, and that the ‘young’ pattern of molecular signalling can reactivate tissue regeneration. The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in tissue-specific stem Cells1,2,3,4,5. A decline in skeletal muscle stem Cell (satellite Cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle1,6. The decline in Hepatic Progenitor Cell proliferation owing to the formation of a complex involving cEBP-α and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver7. To examine the influence of systemic factors on aged Progenitor Cells from these tissues, we established parabiotic pairings (that is, a shared circulatory system) between young and old mice (heterochronic parabioses), exposing old mice to factors present in young serum. Notably, heterochronic parabiosis restored the activation of Notch signalling as well as the proliferation and regenerative capacity of aged satellite Cells. The exposure of satellite Cells from old mice to young serum enhanced the expression of the Notch ligand (Delta), increased Notch activation, and enhanced proliferation in vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte proliferation and restored the cEBP-α complex to levels seen in young animals. These results suggest that the age-related decline of Progenitor Cell activity can be modulated by systemic factors that change with age.

  • Rejuvenation of aged Progenitor Cells by exposure to a young systemic environment
    Nature, 2005
    Co-Authors: Irina M. Conboy, Eric R. Girma, Irving L. Weismann, Amy J. Wagers, Michael J. Conboy, Thomas A Rando
    Abstract:

    The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in tissue-specific stem Cells. A decline in skeletal muscle stem Cell (satellite Cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle. The decline in Hepatic Progenitor Cell proliferation owing to the formation of a complex involving cEBP-alpha and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver. To examine the influence of systemic factors on aged Progenitor Cells from these tissues, we established parabiotic pairings (that is, a shared circulatory system) between young and old mice (heterochronic parabioses), exposing old mice to factors present in young serum. Notably, heterochronic parabiosis restored the activation of Notch signalling as well as the proliferation and regenerative capacity of aged satellite Cells. The exposure of satellite Cells from old mice to young serum enhanced the expression of the Notch ligand (Delta), increased Notch activation, and enhanced proliferation in vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte proliferation and restored the cEBP-alpha complex to levels seen in young animals. These results suggest that the age-related decline of Progenitor Cell activity can be modulated by systemic factors that change with age.

Juha Kere - One of the best experts on this subject based on the ideXlab platform.

  • ketogenic diet attenuates hepatopathy in mouse model of respiratory chain complex iii deficiency caused by a bcs1l mutation
    Scientific Reports, 2017
    Co-Authors: Janne Purhonen, Matthias Morgelin, Jayasimman Rajendran, Kristiina Uusirauva, Shintaro Katayama, Kaarel Krjutskov, Elisabet Einarsdottir, Vidya Velagapudi, Juha Kere
    Abstract:

    Mitochondrial disorders are among the most prevalent inborn errors of metabolism but largely lack treatments and have poor outcomes. High-fat, low-carbohydrate ketogenic diets (KDs) have shown beneficial effects in mouse models of mitochondrial myopathies, with induction of mitochondrial biogenesis as the suggested main mechanism. We fed KD to mice with respiratory chain complex III (CIII) deficiency and progressive hepatopathy due to mutated BCS1L, a CIII assembly factor. The mutant mice became persistently ketotic and tolerated the KD for up to 11 weeks. Liver disease progression was attenuated by KD as shown by delayed fibrosis, reduced Cell death, inhibition of Hepatic Progenitor Cell response and stellate Cell activation, and normalization of liver enzyme activities. Despite no clear signs of increased mitochondrial biogenesis in the liver, CIII assembly and activity were improved and mitochondrial morphology in hepatocytes normalized. Induction of Hepatic glutathione transferase genes and elevated total glutathione level were normalized by KD. Histological findings and transcriptome changes indicated modulation of liver macrophage populations by the mutation and the diet. These results reveal a striking beneficial Hepatic response to KD in mice with mitochondrial hepatopathy and warrant further investigations of dietary modification in the management of these conditions in patients.