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Johan Auwerx

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Publications associées (283)

NAD(+) homeostasis in health and disease

Elena Katsyuba, Johan Auwerx, Mario Romani, Dina Hofer

The conceptual evolution of nicotinamide adenine dinucleotide (NAD(+)) from being seen as a simple metabolic cofactor to a pivotal cosubstrate for proteins regulating metabolism and longevity, including the sirtuin family of protein deacylases, has led to ...

2020

NCoR1 Protects Mice From Dextran Sodium Sulfate Induced Colitis by Guarding Colonic Crypt Cells From Luminal Insult

Johan Auwerx

BACKGROUND & AIMS: Colonic stem cells are essential for producing the mucosal lining, which in turn protects stem cells from insult by luminal factors. Discovery of genetic and biochemical events that control stem cell proliferation and differentiation can ...

2020

Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age

Johan Auwerx, Norman Lionel Moullan

Adipose tissue eosinophils (ATEs) are important in the control of obesity-associated inflammation and metabolic disease. However, the way in which ageing impacts the regulatory role of ATEs remains unknown. Here, we show that ATEs undergo major age-related ...

2020

Growth differentiation factor 15 protects against the aging-mediated systemic inflammatory response in humans and mice

Johan Auwerx, Dongryeol Ryu, Jun Yong Kim, Ludger Jan Elzuë Goeminne

Mitochondrial dysfunction is associated with aging-mediated inflammatory responses, leading to metabolic deterioration, development of insulin resistance, and type 2 diabetes. Growth differentiation factor 15 (GDF15) is an important mitokine generated in r ...

2020

Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism

Johan Auwerx, Martin Rainer Wohlwend

Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors that are characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with ...

Nature Research2020

Long noncoding RNA SNHG12 integrates a DNA-PK-mediated DNA damage response and vascular senescence

Johan Auwerx, Norman Lionel Moullan, Lei Chen

Long noncoding RNAs (lncRNAs) are emerging regulators of biological processes in the vessel wall; however, their role in atherosclerosis remains poorly defined. We used RNA sequencing to profile lncRNAs derived specifically from the aortic intima of Ldlr(- ...

AMER ASSOC ADVANCEMENT SCIENCE2020

PHD3 Loss Promotes Exercise Capacity and Fat Oxidation in Skeletal Muscle

Daniel Garcia, Johan Auwerx, Hao Li

Rapid alterations in cellular metabolism allow tissues to maintain homeostasis during changes in energy availability. The central metabolic regulator acetyl-CoA carboxylase 2 (ACC2) is robustly phosphorylated during cellular energy stress by AMP-activated ...

Cell Press2020

Nicotinamide Pathway-Dependent Sirt1 Activation Restores Calcium Homeostasis to Achieve Neuroprotection in Spinocerebellar Ataxia Type 7

Johan Auwerx, Karim Laurent Gariani

Sirtuin 1 (Sirt1) is a NAD(+)-dependent deacetylase capable of countering age-related neurodegeneration, but the basis of Sirt1 neuroprotection remains elusive. Spinocerebellar ataxia type 7 (SCA7) is an inherited CAG-polyglutamine repeat disorder. Transcr ...

2020

Mitochondrial Deacetylase Sirt3 Reduces Vascular Dysfunction and Hypertension While Sirt3 Depletion in Essential Hypertension Is Linked to Vascular Inflammation and Oxidative Stress

Johan Auwerx

Rationale: Hypertension represents a major risk factor for stroke, myocardial infarction, and heart failure and affects 30% of the adult population. Mitochondrial dysfunction contributes to hypertension, but specific mechanisms are unclear. The mitochondri ...

2020

Enoxacin induces oxidative metabolism and mitigates obesity by regulating adipose tissue miRNA expression

Johan Auwerx, Tanes Imamura de Lima

MicroRNAs (miRNAs) have been implicated in oxidative metabolism and brown/beige adipocyte identity. Here, we tested whether widespread changes in miRNA expression promoted by treatment with the small-molecule enoxacin cause browning and prevent obesity. En ...

AMER ASSOC ADVANCEMENT SCIENCE2020

Evaluation of the NAD(+) biosynthetic pathway in ALS patients and effect of modulating NAD(+) levels in hSOD1-linked ALS mouse models

Johan Auwerx

Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons. Astrocytes from diverse ALS models induce motor neuron death in co-culture. Enhancing NAD(+) availability, or increasing the expression of the NAD(+)-depende ...

2020

The Detection of Early Epigenetic Inheritance of Mitochondrial Stress in C. Elegans with a Microfluidic Phenotyping Platform

Martinus Gijs, Johan Auwerx, Matteo Cornaglia, Hüseyin Baris Atakan

Fluctuations and deterioration in environmental conditions potentially have a phenotypic impact that extends over generations. Transgenerational epigenetics is the defined term for such intergenerational transient inheritance without an alteration in the D ...

Nature Research2019

Cross-species functional modules link proteostasis to human normal aging

Johan Auwerx, Andrea Komljenovic, Hao Li, Vincenzo Sorrentino

The evolutionarily conserved nature of the few well-known anti-aging interventions that affect lifespan, such as caloric restriction, suggests that aging-related research in model organisms is directly relevant to human aging. Since human lifespan is a com ...

2019

The RNA-Binding Protein PUM2 Impairs Mitochondrial Dynamics and Mitophagy During Aging

Bernard Schneider, Graham Knott, Kristina Schoonjans, Johan Auwerx, Adrienne Joëlle Laurence Mottis, Vera Monica Lemos Da Silva, Hao Li, Vincenzo Sorrentino, Davide D'Amico, Mario Romani, Francesca Potenza

Little information is available about how post-transcriptional mechanisms regulate the aging process. Here, we show that the RNA-binding protein Pumilio2 (PUM2), which is a translation repressor, is induced upon aging and acts as a negative regulator of li ...

CELL PRESS2019

The virtuous cycle of human genetics and mouse models in drug discovery

Johan Auwerx

Ongoing studies in many species seek to understand the origins, architecture and consequences of phenotypic variation under normal and dysfunctional conditions, with the aim of identifying targets for intervention that can prevent, stabilize or reverse dis ...

NATURE PUBLISHING GROUP2019

MicroRNA-382 silencing induces a mitonuclear protein imbalance and activates the mitochondrial unfolded protein response in muscle cells

Johan Auwerx, Norman Lionel Moullan, Pénélope Andreux, Xu Wang

Proper mitochondrial function plays a central role in cellular metabolism. Various diseases as well as aging are associated with diminished mitochondrial function. Previously, we identified 19 miRNAs putatively involved in the regulation of mitochondrial m ...

2019

Regulation of NAD plus biosynthesis pathway in chronic kidney disease

Renuga Devi Rajaram, Johan Auwerx, Adrienne Joëlle Laurence Mottis

E M H SWISS MEDICAL PUBLISHERS LTD2019

Identifying gene function and module connections by the integration of multispecies expression compendia

Stephan Morgenthaler, Elena Katsyuba, Kristina Schoonjans, Johan Auwerx, Fabrice David, Maroun Bou Sleiman, Daria Rukina, Andrea Komljenovic, Hao Li, Qingyao Huang, Yang Li, Changmyung Oh, Wen Gao

The functions of many eukaryotic genes are still poorly understood. Here, we developed and validated a new method, termed GeneBridge, which is based on two linked approaches to impute gene function and bridge genes with biological processes. First, Gene-Mo ...

Cold Spring Harbor Laboratory2019

Mitochondrial haplotypes affect metabolic phenotypes in the Drosophila Genetic Reference Panel

Adamantia Kapopoulou, Bart Deplancke, Johan Auwerx, Roel Paulus Josephus Bevers, Virginie Sandra Braman, Maria Litovchenko, Brian Dennis Hollis

The nature and extent of mitochondrial DNA variation in a population and how it affects traits is poorly understood. Here we resequence the mitochondrial genomes of 169 Drosophila Genetic Reference Panel lines, identifying 231 variants that stratify along ...

2019

Niacin: an old lipid drug in a new NAD(+) dress

Elena Katsyuba, Johan Auwerx, Mario Romani, Dina Hofer

Niacin, the first antidyslipidemic drug, has been at the center stage of lipid research for many decades before the discovery of statins. However, to date, despite its remarkable effects on lipid profiles, the clinical outcomes of niacin treatment on cardi ...

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC2019

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