Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To achieve a long life span, animals must be resistant to various injuries as well as avoid or delay lethality from age-dependent diseases. Reduced expression of the mitochondrial enzyme CLK-1/MCLK1 (a.k.a. Coq7), a mitochondrial hydroxylase that is necessary for the biosynthesis of ubiquinone (UQ), extends lifespan in Caenorhabditiselegans and in mice. Here, we show that long-lived Mclk1(+/)(-) mutants have enhanced resistance to neurological damage following global cerebral ischemia-reperfusion (I/R) injury induced by transient bilateral common carotid artery occlusion (BCCAO). Both young ( approximately 100days old) and relatively aged ( approximately 450days old) mutants display increased resistance as indicated by a significant decrease in the amount of degenerating cells observed in forebrain cortex and in hippocampal areas after ischemia and reperfusion. Furthermore, less oxidative damage resulting from the procedure was measured in the brain of young Mclk1(+/)(-) animals. The finding that both young and old mutants are protected indicates that this is a basic phenotype of these mutants and not a secondary consequence of their slow rate of aging. Thus, the partial resistance to I/R injury suggests that Mclk1(+/)(-) mutants have an enhanced recovery potential following age-dependant vascular accidents, which correlates well with their longer survival. By relating this neuroprotective effect to previously reported characteristics of the Mclk1(+/)(-) phenotype, including altered mitochondrial metabolism and increased HIF-1alpha expression, this study establishes these mutants as useful models to analyze the mechanisms underlying tolerance to ischemia, particularly those associated with ischemic preconditioning, as well as to clarify the relation between aging and age-dependent diseases.
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PMID:Lifelong protection from global cerebral ischemia and reperfusion in long-lived Mclk1(+/)(-) mutants. 2017 Jun 52