Reduced Phosphorylation of Transcription Factor Elk-1 in Cultured Fibroblasts of a Patient with Premature Aging Syndrome and Insulin Resistance

2005 ◽  
Vol 113 (02) ◽  
pp. 94-101 ◽  
Author(s):  
B. Knebel ◽  
H. Avci ◽  
C. Bullmann ◽  
J. Kotzka ◽  
D. Müller-Wieland
Keyword(s):  
Insulin Resistance ◽  
Transcription Factor ◽  
Premature Aging ◽  
Cultured Fibroblasts ◽  
Premature Aging Syndrome

scholarly journals Podiatric complications during a premature aging syndrome: Rare case

2016 ◽  
Vol 59 ◽  
pp. e28-e29
Author(s):  
Siham Zahi ◽  
Laila Mahir ◽  
Soumia Meftah ◽  
Fatima Lmidmani ◽  
Abdellatif El fatimi
Keyword(s):  
Rare Case ◽  
Premature Aging ◽  
Premature Aging Syndrome

scholarly journals Supplementing Glycine and N-acetylcysteine (GlyNAC) in Aging HIV Patients Improves Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Endothelial Dysfunction, Insulin Resistance, Genotoxicity, Strength, and Cognition: Results of an Open-Label Clinical Trial

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 390
Author(s):  
Premranjan Kumar ◽  
Chun Liu ◽  
James W. Suliburk ◽  
Charles G. Minard ◽  
Raja Muthupillai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Clinical Trial ◽  
Cognitive Decline ◽  
Muscle Protein ◽  
Glucose Production ◽  
Premature Aging ◽  
Open Label ◽  
Breakdown Rates ◽  
Genomic Damage

Background: Patients with HIV (PWH) develop geriatric comorbidities, including functional and cognitive decline at a younger age. However, contributing mechanisms are unclear and interventions are lacking. We hypothesized that deficiency of the antioxidant protein glutathione (GSH) contributes to multiple defects representing premature aging in PWH, and that these defects could be improved by supplementing the GSH precursors glycine and N-acetylcysteine (GlyNAC). Methods: We conducted an open label clinical trial where eight PWH and eight matched uninfected-controls were studied at baseline. PWH were studied again 12-weeks after receiving GlyNAC, and 8-weeks after stopping GlyNAC. Controls did not receive supplementation. Outcome measures included red-blood cell and muscle GSH concentrations, mitochondrial function, mitophagy and autophagy, oxidative stress, inflammation, endothelial function, genomic damage, insulin resistance, glucose production, muscle-protein breakdown rates, body composition, physical function and cognition. Results: PWH had significant defects in measured outcomes, which improved with GlyNAC supplementation. However, benefits receded after stopping GlyNAC. Conclusions: This open label trial finds that PWH have premature aging based on multiple biological and functional defects, and identifies novel mechanistic explanations for cognitive and physical decline. Nutritional supplementation with GlyNAC improves comorbidities suggestive of premature aging in PWH including functional and cognitive decline, and warrants additional investigation.

Diseases of adipose tissue: genetic and acquired lipodystrophies

2005 ◽  
Vol 33 (5) ◽  
pp. 1073-1077 ◽  
Author(s):  
J. Capeau ◽  
J. Magré ◽  
O. Lascols ◽  
M. Caron ◽  
V. Béréziat ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Antiretroviral Drugs ◽  
Premature Aging ◽  
Peroxisome Proliferator ◽  
Loss Of Function ◽  
Lifestyle Modifications ◽  
Metabolic Alterations ◽  
Severe Insulin Resistance ◽  
The Metabolic Syndrome ◽  
Triacylglycerol Synthesis

Human lipodystrophies represent a group of diseases characterized by altered body fat amount and/or repartition and major metabolic alterations with insulin resistance leading to diabetic complications and increased cardiovascular and hepatic risk. Genetic forms of lipodystrophies are rare. Congenital generalized lipodystrophy or Berardinelli–Seip syndrome, autosomal recessive, is characterized by a complete early lipoatrophy and severe insulin resistance and results, in most cases, from mutations either in the seipin gene of unknown function or AGPAT2 encoding an enzyme involved in triacylglycerol synthesis. The Dunnigan syndrome [FPLD2 (familial partial lipodystrophy of the Dunnigan type)] is due to mutations in LMNA encoding the lamin A/C, belonging to the complex group of laminopathies that could comprise muscular and cardiac dystrophies, neuropathies and syndromes of premature aging. Some FPLDs are linked to loss-of-function mutations in the PPAR-γ gene (peroxisome-proliferator-activated receptor γ; FPLD3) with severe metabolic alterations but a less severe lipodystrophy compared with FPLD2. The metabolic syndrome, acquired, represents the most common form of lipodystrophy. HIV-infected patients often present lipodystrophies, mainly related to side effects of antiretroviral drugs together with insulin resistance and metabolic alterations. Such syndromes help to understand the mechanisms involved in insulin resistance resulting from altered fat repartition and could benefit from insulin-sensitizing effects of lifestyle modifications or of specific medications.

Mef2C Is a Lineage-Restricted Target Gene of Scl/Tal1 and Regulates Megakaryopoiesis and B-Cell Homeostasis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 278-278
Author(s):  
Katrin E Rhodes ◽  
Christos Gekas ◽  
Laurraine Gereige ◽  
Hildur Helgadottir ◽  
Roberto Ferrari ◽  
...  
Keyword(s):  
Transcription Factor ◽  
B Cell ◽  
Muscle Development ◽  
Target Genes ◽  
Fetal Liver ◽  
Premature Aging ◽  
Bhlh Transcription Factor ◽  
Functional Requirements ◽  
B Lymphoid ◽  
Deficient Mice

Abstract The bHLH transcription factor stem cell leukemia/T-cell acute leukemia gene (Scl/Tal1) is a master regulator for hematopoiesis, essential for hematopoietic specification and proper differentiation of the erythroid and megakaryocyte lineages. However, the critical downstream targets of Scl remain undefined. To identify Scl target genes in hematopoietic cells, we performed gene expression analysis on HOX11-immortalized Sclfl/fl fetal liver cell lines. Analysis of the top 50 downregulated genes revealed several genes related to hematopoiesis including erythroid and megakaryocyte development, vasculogenesis, as well as genes/unknown ESTs that have not been previously linked to blood development. One of the top downregulated genes was transcription factor myocyte enhancer factor 2C (Mef2C). Mef2C−/− embryos die at E9.5, the same time as Scl−/− embryos, and exhibit severe defects in cardiac and muscle development. Analysis of Mef2C−/− embryos showed that, Mef2C, in contrast to Scl, is not required for specification into primitive or definitive hematopoietic lineages. To bypass the embryonic lethality, we utilized a conditionally targeted Mef2Cfl/fl strain and crossed it with a hematopoietic cell-specific VavCre strain that deactivates Mef2C shortly after the emergence of HSCs. Interestingly, adult VavCre+Mef2Cfl/fl mice exhibited severe platelet defects highly reminiscent to those observed in Scl deficient mice. The platelet counts were reduced, while platelet size was increased and the platelet shape and granularity was altered. Furthermore, megakaryopoiesis was severely impaired in vitro. ChIP-on-chip analysis revealed that Mef2C is directly regulated by Scl in megakaryocytic cells, but not in erythroid cells. In addition, an Scl independent requirement for Mef2C in B-lymphoid homeostasis was observed in Mef2C-deficient mice, characterized as severe age-dependent reductions of specific B-cell progenitor populations reminiscent of premature aging. In summary, this work identifies Mef2C as an integral member of hematopoietic transcription factors with distinct upstream regulatory mechanisms and functional requirements in megakaryocyte and B-lymphoid lineages.

scholarly journals Sex Hormone-Binding Globulin Gene Expression and Insulin Resistance

2014 ◽  
Vol 99 (12) ◽  
pp. E2780-E2788 ◽  
Author(s):  
Stephen J. Winters ◽  
Jyothi Gogineni ◽  
Marjan Karegar ◽  
Charles Scoggins ◽  
Chris A. Wunderlich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Transcription Factor ◽  
Outcome Measures ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Strong Positive Correlation ◽  
Model Assessment ◽  
Nutritional Regulation ◽  
Hormone Binding

Context: The plasma level of sex hormone binding globulin (SHBG), a glycoprotein produced by hepatocytes, is subject to genetic, hormonal, metabolic, and nutritional regulation, and is a marker for the development of the metabolic syndrome and diabetes. Objective: Because the mechanism for these associations is unclear, and no studies of SHBG gene expression in humans have been published, SHBG mRNA was measured in human liver samples and related to anthropometric data. Setting: Inpatients at a private, nonprofit, university-associated hospital were studied. Participants: Subjects were fifty five adult men and women undergoing hepatic resection as treatment for cancer. Main Outcome Measures: Main outcome measures were SHBG mRNA and serum SHBG levels. Results: SHBG mRNA was a strong predictor of serum SHBG with higher levels of the mRNA and protein in women than in men. The relationship between SHBG mRNA and circulating SHBG differed in males and females consistent with a sex difference in post-transcriptional regulation. A strong positive correlation was found between the level of the mRNA for the transcription factor HNF4α and SHBG mRNA. Insulin resistance (IR), assessed by homeostatis model assessment, was related inversely to SHBG mRNA and to HNF4α mRNA as well as to circulating SHBG levels. These mRNAs, as well as serum SHBG, were higher when the hepatic triglyceride concentration was low, and decreased with increasing body mass index but were unrelated to age. Conclusions: Fat accumulation in liver and IR are important determinants of SHBG gene expression and thereby circulating SHBG levels that are perhaps mediated through effects on the transcription factor HNF4α. These findings provide a potential mechanism to explain why low SHBG predicts the development of type 2 diabetes.

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