European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands; Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany
Laura M Zidek
Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany
Tobias Ackermann
European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
Tristan de Jong
European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
Peng Liu
Institute for Comparative Molecular Endocrinology, University of Ulm, Ulm, Germany
Verena Kliche
Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany
Mohamad Amr Zaini
European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
Gertrud Kortman
European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
Liesbeth Harkema
Dutch Molecular Pathology Centre, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands
Dineke S Verbeek
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Jan P Tuckermann
Institute for Comparative Molecular Endocrinology, University of Ulm, Ulm, Germany
Julia von Maltzahn
Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany
Alain de Bruin
Dutch Molecular Pathology Centre, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Victor Guryev
European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
Zhao-Qi Wang
Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany
European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands; Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany
Ageing is associated with physical decline and the development of age-related diseases such as metabolic disorders and cancer. Few conditions are known that attenuate the adverse effects of ageing, including calorie restriction (CR) and reduced signalling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Synthesis of the metabolic transcription factor C/EBPβ-LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame (uORF) in the Cebpb-mRNA. Here, we describe that reduced C/EBPβ-LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice. Moreover, female C/EBPβΔuORF mice display an extended lifespan. Since LIP levels increase upon aging in wild type mice, our data reveal an important role for C/EBPβ in the aging process and suggest that restriction of LIP expression sustains health and fitness. Thus, therapeutic strategies targeting C/EBPβ-LIP may offer new possibilities to treat age-related diseases and to prolong healthspan.
