Correction: Corrigendum: Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects

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.

High-Throughput Metabolomics for Discovering Potential Biomarkers and Identifying Metabolic Mechanisms in Aging and Alzheimer’s Disease

“…Arginine and proline metabolism contains several metabolic pathways we mentioned in the AD-related pathways, such glutathione, glycine, and polyamine metabolism. Evidence has shown that these pathways are related to aging ( Minois et al, 2011 ; Hashizume et al, 2015 ; Weschawalit et al, 2017 ). We can see that arginine and proline metabolism has been shown to play a role in prospective studies of the progression from no disease to MCI and eventually AD; likewise, arginine and proline metabolism appears in the pathways related to natural aging.…”

LOTUS overexpression via ex vivo gene transduction further promotes recovery of motor function following human iPSC-NS/PC transplantation for contusive spinal cord injury

“…Mouse LOTUS (mLOTUS) cDNA and the Venus fluorescent protein ( Nagai et al., 2002 ; Duran-Avelar et al., 2018 ) gene connected by an internal ribosomal entry site (IRES) were cloned into the lentiviral vector CSII-EF1α, yielding pCSII-EF1α-mLOTUS-IRES-Venus ( Figure 1 A) ( Iida et al., 2017 ). Recombinant lentiviral vector production and titer determination were performed as described previously ( Hashizume et al., 2015 ).…”