Publications by Richardus Houtkooper

ACMSD INHIBITION REDUCES HEPATIC INFLAMMATION AND FIBROSIS IN A MURINE THERMONEUTRALITY MODEL OF NASH

Johan Auwerx, Richardus Houtkooper, Krisztian Homicsko, Maroun Bou Sleiman, Xiaoxu Li, Sandra Rodriguez Lopez, Jia Liu, Keno Strotjohann

Lippincott Williams & Wilkins2023

INHIBITING SARM1 IS MORE EFFICACIOUS THAN NICOTINAMIDE RIBOSIDE SUPPLEMENTATION FOR THE TREATMENT OF A MOUSE MODEL WITH NAFLD/NASH

Johan Auwerx, Richardus Houtkooper, Krisztian Homicsko, Maroun Bou Sleiman, Xiaoxu Li, Sandra Rodriguez Lopez, Jia Liu, Keno Strotjohann

Lippincott Williams & Wilkins2023

The mouse metallomic landscape of aging and metabolism

Johan Auwerx, Richardus Houtkooper, Evan Graehl Williams, Pooja Jha, Jean-David Horacio Morel, Ludger Jan Elzuë Goeminne

The metallome is crucial for normal cell functioning but remains largely overlooked in mammals. Here the authors analyze the metallome and copper and zinc isotope compositions in aging mice and show networks of interactions that are organ-specific, age-dep ...

Nature Research2022

Reduced ech-6 expression attenuates fat-induced lifespan shortening in C. elegans

Richardus Houtkooper, Wen Gao, Yuan Liu

Deregulated energy homeostasis represents a hallmark of aging and results from complex gene-by-environment interactions. Here, we discovered that reducing the expression of the gene ech-6 encoding enoyl-CoA hydratase remitted fat diet-induced deleterious e ...

Nature Portfolio2022

Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans

Johan Auwerx, Richardus Houtkooper

Background: Nicotinamide riboside (NR) is an NAD(+) precursor that boosts cellular NAD(+) concentrations. Preclinical studies have shown profound metabolic health effects after NR supplementation. ...

OXFORD UNIV PRESS2020

Confounding factors from inducible systems for spatiotemporal gene expression regulation

Johan Auwerx, Richardus Houtkooper

Spatiotemporally regulated targeted gene manipulation is a common way to study the effect of gene variants on phenotypic traits, but the Cre/loxP and Tet-On/Tet-Off systems can affect whole-organism physiology and function due to off-target effects. We hig ...

Rockefeller University Press2020

The Gene-Regulatory Footprint of Aging Highlights Conserved Central Regulators

Johan Auwerx, Richardus Houtkooper, Maroun Bou Sleiman, Xu Wang, Pooja Jha

Many genes and pathways have been linked to aging, yet our understanding of underlying molecular mechanisms is still lacking. Here, we measure changes in the transcriptome, histone modifications, and DNA methylome in three metabolic tissues of adult and ag ...

2020

A reduced form of nicotinamide riboside defines a new path for NAD(+) biosynthesis and acts as an orally bioavailable NAD(+) precursor

Carlos Canto Alvarez, Richardus Houtkooper, Sofia Moco

Objective: A decay in intracellular NAD(+) levels is one of the hallmarks of physiological decline in normal tissue functions. Accordingly, dietary supplementation with NAD(+) precursors can prevent, alleviate, or even reverse multiple metabolic complicati ...

2019

Increased cardiac fatty acid oxidation in a mousemodel with decreasedmalonyl-CoA sensitivity of CPT1B

Johan Auwerx, Richardus Houtkooper

2018

Mfn1 Deficiency in the Liver Protects Against Diet-Induced Insulin Resistance and Enhances the Hypoglycemic Effect of Metformin

Patrick Descombes, Carlos Canto Alvarez, Richardus Houtkooper, Sylviane Métairon, Joanna Ratajczak, Catherine Maclachlan, Wen Gao

Mitochondrial function can be influenced by mitochondrial shape and connectivity with other cellular organelles through fusion and fission processes. Disturbances in mitochondrial architecture and mitochondrial fusion related genes are observed in situatio ...

American Diabetes Association2016

Type 5 adenylyl cyclase disruption leads to enhanced exercise performance

Johan Auwerx, Richardus Houtkooper, Laurent Mouchiroud, Jie Zhang

The most important physiological mechanism mediating enhanced exercise performance is increased sympathetic, beta adrenergic receptor (beta-AR), and adenylyl cyclase (AC) activity. This is the first report of decreased AC activity mediating increased exerc ...

Wiley-Blackwell2015

Tetracycline Antibiotics Impair Mitochondrial Function and Its Experimental Use Confounds Research

Johan Auwerx, Richardus Houtkooper, Laurent Mouchiroud

Tetracyclines, a class of antibiotics that target bacterial translation, are commonly used in research for inducible gene expression using Tet-ON/Tet-OFF systems. However, such tetracycline-inducible systems carry a risk. Given that mitochondria have a "ba ...

American Association for Cancer Research2015

Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research

Michael Vincent Frochaux, Bart Deplancke, Johan Auwerx, Richardus Houtkooper, Norman Lionel Moullan, Evan Graehl Williams, Dongryeol Ryu, Adrienne Joëlle Laurence Mottis, Laurent Mouchiroud, Virginija Jovaisaite, Xu Wang

In recent years, tetracyclines, such as doxycycline, have become broadly used to control gene expression by virtue of the Tet-on/Tet-off systems. However, the wide range of direct effects of tetracycline use has not been fully appreciated. We show here tha ...

Elsevier2015

A method to identify and validate mitochondrial modulators using mammalian cells and the worm C-elegans

Sabrina Bichet, Johan Auwerx, Richardus Houtkooper, Norman Lionel Moullan, Pénélope Andreux, Adrienne Joëlle Laurence Mottis, Laurent Mouchiroud, Virginija Jovaisaite, Xu Wang

Mitochondria are semi-autonomous organelles regulated by a complex network of proteins that are vital for many cellular functions. Because mitochondrial modulators can impact many aspects of cellular homeostasis, their identification and validation has pro ...

Nature Publishing Group2014

Mitonuclear protein imbalance as a conserved longevity mechanism

Graham Knott, Elena Katsyuba, Johan Auwerx, Richardus Houtkooper, Norman Lionel Moullan, Dongryeol Ryu, Laurent Mouchiroud

Longevity is regulated by a network of closely linked metabolic systems. We used a combination of mouse population genetics and RNA interference in Caenorhabditis elegans to identify mitochondrial ribosomal protein S5 (Mrps5) and other mitochondrial riboso ...

Nature Publishing Group2013

Methods of treating mitochondrial dysfunction

Johan Auwerx, Richardus Houtkooper, Laurent Mouchiroud

The present invention provides methods of treating various disorders associated with mitochondrial dysfunction, including but not limited to metabolic disorders, neurodegenerative diseases, chronic inflammatory diseases, and diseases of aging. ...

2013

Pharmacological approaches to restore mitochondrial function

Johan Auwerx, Richardus Houtkooper, Pénélope Andreux

Mitochondrial dysfunction is not only a hallmark of rare inherited mitochondrial disorders but also implicated in age-related diseases, including those that affect the metabolic and nervous system, such as type 2 diabetes and Parkinson's disease. Numerous ...

Nature Publishing Group2013

Mitochondrial ribosomal proteins as aging regulators

Johan Auwerx, Richardus Houtkooper, Laurent Mouchiroud

The present invention relates to methods of increasing lifespan, delaying aging, and/or preventing or treating an age-related disease or a mitochondrialdisease in a subject, comprising inducing a nuclear-mitochondrial OXPHOS protein dyssynchrony, including ...

2013

Aging biomarkers

Johan Auwerx, Richardus Houtkooper

The present invention relates to novel biomarkers for aging and healthspan, methods and uses thereof, in particular, for determining the biological age of a subject and/or preventing or delaying aging process in a subject, and kits for use in said methods. ...

2013

The RNA-binding protein Imp2 regulates oxidative phosporylation that is key to glioblastoma cancer stem cell maintenance

Michalina Janiszewska, Richardus Houtkooper, Ivan Stamenkovic

Federation Amer Soc Exp Biol2012