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We are analyzing https://www.nature.com/articles/s41598-017-18828-3.

Title:
Mice deficient in the Shmt2 gene have mitochondrial respiration defects and are embryonic lethal | Scientific Reports
Description:
Accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for human aging and age-associated mitochondrial respiration defects. However, our previous findings suggested an alternative hypothesis of human aging—that epigenetic changes but not mutations regulate age-associated mitochondrial respiration defects, and that epigenetic downregulation of nuclear-coded genes responsible for mitochondrial translation [e.g., glycine C-acetyltransferase (GCAT), serine hydroxymethyltransferase 2 (SHMT2)] is related to age-associated respiration defects. To examine our hypothesis, here we generated mice deficient in Gcat or Shmt2 and investigated whether they have respiration defects and premature aging phenotypes. Gcat-deficient mice showed no macroscopic abnormalities including premature aging phenotypes for up to 9 months after birth. In contrast, Shmt2-deficient mice showed embryonic lethality after 13.5 days post coitum (dpc), and fibroblasts obtained from 12.5-dpc Shmt2-deficient embryos had respiration defects and retardation of cell growth. Because Shmt2 substantially controls production of N-formylmethionine-tRNA (fMet-tRNA) in mitochondria, its suppression would reduce mitochondrial translation, resulting in expression of the respiration defects in fibroblasts from Shmt2-deficient embryos. These findings support our hypothesis that age-associated respiration defects in fibroblasts of elderly humans are caused not by mtDNA mutations but by epigenetic regulation of nuclear genes including SHMT2.
Website Age:
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Keywords {🔍}

shmt, gcat, mice, mitochondrial, respiration, defects, pubmed, article, mutations, fig, embryos, google, scholar, cas, embryonic, mef, mtdna, heterozygous, nature, lethality, dpc, mutation, lines, aging, dna, mouse, analysis, nuclear, respiratory, human, ageassociated, mefs, showed, glycine, cells, absence, growth, western, central, gene, blot, protein, metabolism, deficient, fibroblasts, retardation, homozygous, japan, function, data,

Topics {✒️}

nature portfolio professional english-speaking editors scientific research privacy policy advertising nature rev nature med social media nature genet b-lymphoma development nature 429 nature 520 nature reprints jun-ichi hayashi thermo fisher scientific lymphoma development 5-aminoimidazole-4-carboxamide ribonucleotide accumulation mito-miceδ carrying mtdna published article permissions obvious macroscopic abnormalities author correspondence original author methods ethics statement western blot data produces mtdna-coded subunits premature aging phenotypes showing macroscopic abnormalities privacy nuclear-coded genes responsible embryos produce fmet-trna reduce mitochondrial translation premature ageing age-related respiration deficiency glycine c-acetyltransferase article tani mitochondrial folate pathway respiratory enzyme activity cancer younghwan leekaren premature aging phenotypes9 premature aging phenotype journals search log pvdf blocking reagent western blot analysis full size image inter-mitochondrial complementation accumulate somatic mutations mitochondrial diseases caused mitochondrial respiratory function1

Questions {❓}

  • Mitochondrial DNA mutations and aging: devils in the details?
  • The mitochondrial theory of aging: dead or alive?

Schema {🗺️}

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External Links {🔗}(143)

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  • mxb-002c5801.gslb.pphosted.com

Name Servers:

  • pdns1.ultradns.net
  • pdns2.ultradns.net
  • pdns3.ultradns.org
  • pdns4.ultradns.org
  • pdns5.ultradns.info
  • pdns6.ultradns.co.uk

CDN Services {📦}

  • Crossref

4.09s.