Редактирование: GCAT (раздел)

==Publications==

{{medline-entry
|title=Impairing L-Threonine Catabolism Promotes Healthspan through Methylglyoxal-Mediated Proteohormesis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29551589
|abstract=Whether and how regulation of genes and pathways contributes to physiological aging is topic of intense scientific debate. By performing an RNA expression-based screen for genes downregulated during aging of three different species, we identified glycine-C-acetyltransferase ([[GCAT]], EC 2.3.1.29). Impairing gcat expression promotes the lifespan of C. elegans by interfering with threonine catabolism to promote methylglyoxal (MGO; CAS 78-98-8) formation in an amine oxidase-dependent manner. MGO is a reactive dicarbonyl inducing diabetic complications in mammals by causing oxidative stress and damaging cellular components, including proteins. While high concentrations of MGO consistently exert toxicity in nematodes, we unexpectedly find that low-dose MGO promotes lifespan, resembling key mediators of gcat impairment. These were executed by the ubiquitin-proteasome system, namely PBS-3 and RPN-6.1 subunits, regulated by the stress-responsive transcriptional regulators SKN-1/NRF2 and HSF-1. Taken together, [[GCAT]] acts as an evolutionary conserved aging-related gene by orchestrating an unexpected nonlinear impact of proteotoxic MGO on longevity.
|mesh-terms=* Acetyltransferases
* Animals
* Caenorhabditis elegans
* Caenorhabditis elegans Proteins
* DNA-Binding Proteins
* Longevity
* Oxidative Stress
* Proteasome Endopeptidase Complex
* Pyruvaldehyde
* Signal Transduction
* Threonine
* Transcription Factors
|keywords=* aging
* diabetes
* healthspan
* hormesis
* lifespan
* longevity
* metabolism
* proteostasis
* proteotoxicity
* reactive oxygen species
|full-text-url=https://sci-hub.do/10.1016/j.cmet.2018.02.004
}}
{{medline-entry
|title=Epigenetic regulation of the nuclear-coded [[GCAT]] and [[SHMT2]] genes confers human age-associated mitochondrial respiration defects.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26000717
|abstract=Age-associated accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for the age-associated mitochondrial respiration defects found in elderly human subjects. We carried out reprogramming of human fibroblast lines derived from elderly subjects by generating their induced pluripotent stem cells (iPSCs), and examined another possibility, namely that these aging phenotypes are controlled not by mutations but by epigenetic regulation. Here, we show that reprogramming of elderly fibroblasts restores age-associated mitochondrial respiration defects, indicating that these aging phenotypes are reversible and are similar to differentiation phenotypes in that both are controlled by epigenetic regulation, not by mutations in either the nuclear or the mitochondrial genome. Microarray screening revealed that epigenetic downregulation of the nuclear-coded [[GCAT]] gene, which is involved in glycine production in mitochondria, is partly responsible for these aging phenotypes. Treatment of elderly fibroblasts with glycine effectively prevented the expression of these aging phenotypes. 
|mesh-terms=* Acyltransferases
* Aged, 80 and over
* Aging
* Cell Differentiation
* Cell Line
* Cellular Reprogramming
* Child
* DNA, Mitochondrial
* Epigenesis, Genetic
* Fibroblasts
* Gene Dosage
* Glycine
* Glycine Hydroxymethyltransferase
* Humans
* Induced Pluripotent Stem Cells
* Infant
* Lipase
* Mitochondria
* Oligonucleotide Array Sequence Analysis
* Oxygen Consumption
* Phenotype
* RNA Interference
* RNA, Small Interfering
* Reactive Oxygen Species
* Real-Time Polymerase Chain Reaction
* Sequence Analysis, DNA

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5377050
}}