15 research outputs found

    A nuclear role for the respiratory enzyme CLK-1 in regulating mitochondrial stress responses and longevity

    Get PDF
    The coordinated regulation of mitochondrial and nuclear activities is essential for cellular respiration and its disruption leads to mitochondrial dysfunction, a hallmark of ageing. Mitochondria communicate with nuclei through retrograde signalling pathways that modulate nuclear gene expression to maintain mitochondrial homeostasis. The monooxygenase CLK-1 (human homologue COQ7) was previously reported to be mitochondrial, with a role in respiration and longevity. We have uncovered a distinct nuclear form of CLK-1 that independently regulates lifespan. Nuclear CLK-1 mediates a retrograde signalling pathway that is conserved from Caenorhabditis elegans to humans and is responsive to mitochondrial reactive oxygen species, thus acting as a barometer of oxidative metabolism. We show that, through modulation of gene expression, the pathway regulates both mitochondrial reactive oxygen species metabolism and the mitochondrial unfolded protein response. Our results demonstrate that a respiratory enzyme acts in the nucleus to control mitochondrial stress responses and longevity

    Longevity in mice: is stress resistance a common factor?

    Get PDF
    A positive relationship between stress resistance and longevity has been reported in a multitude of studies in organisms ranging from yeast to mice. Several mouse lines have been discovered or developed that exhibit extended longevities when compared with normal, wild-type mice of the same genetic background. These long-living lines include the Ames dwarf, Snell dwarf, growth hormone receptor knockout (Laron dwarf), IGF-1 receptor heterozygote, Little, α-MUPA knockout, p66shc knockout, FIRKO, mClk-1 heterozygote, thioredoxin transgenic, and most recently the Klotho transgenic mouse. These mice are described in terms of the reported extended lifespans and studies involving resistance to stress. In addition, caloric restriction (CR) and stress resistance are briefly addressed for comparison with genetically altered mice. Although many of the long-living mice have GH/IGF-1/insulin signaling-related alterations and enhanced stress resistance, there are some that exhibit life extension without an obvious link to this hormone pathway. Resistance to oxidative stress is by far the most common system studied in long-living mice, but there is evidence of enhancement of resistance in other systems as well. The differences in stress resistance between long-living mutant and normal mice result from complex interrelationships among pathways that appear to coordinate signals of growth and metabolism, and subsequently result in differences in lifespan

    Animal Models of Human Cerebellar Ataxias: a Cornerstone for the Therapies of the Twenty-First Century

    Full text link

    A linhaça (Linum usitatissimum) como fonte de ácido α-linolênico na formação da bainha de mielina Flaxseed (Linum usitatissimum) as a source of α-linolenic acid in the development of the myelin sheath

    No full text
    A linhaça (Linum usitatissimum) é uma semente oleaginosa que tem sido estudada por seus efeitos benéficos à saúde. É considerada um alimento funcional, pelo fato de ser uma fonte natural de fitoquímicos, e por conter o ácido graxo &#945;-linolênico (C18:3 n-3), que pode ser metabolicamente convertido nos ácidos docosaexahenóico (C22:6 n-3) e eicosapentaenóico (C20:5 n-3), sendo o primeiro essencial para o desenvolvimento do sistema nervoso central. Durante o crescimento do cérebro, há uma grande incorporação do ácido docosaexahenóico, que tem papel importante na formação de suas membranas celulares. Diante disto, esta comunicação visa a abordar os prováveis mecanismos pelos quais o ácido docosaexahenóico, proveniente do ácido &#945;-linolênico presente abundantemente na semente de linhaça, interfere na formação da bainha de mielina, assim como relatar a técnica mais adequada para visualização desta bainha.<br>Flaxseed is an oily seed that has been studied for its beneficial health effects. It is considered a functional food because it is a natural source of phytochemicals and contain the fatty acid &#945;-linolenic acid (C18:3 n-3) that can be metabolically converted into docosahexaenoic acid (C22:6 n-3) and eicosapentaenoic acid (C20:5 n-3). The former is essential for the development of the central nervous system. During brain growth, there is a great incorporation of docosahexaenoic acid which plays in important role in the formation of cell membranes. This communication intended to address the likely mechanisms by which docosahexaenoic acid originating from &#945;-linolenic acid, present in abundance in flaxseed, interferes in the formation of the myelin sheath and report the best method to see this structure
    corecore