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Publication : Reduced expression of C/EBPβ-LIP extends health and lifespan in mice.

First Author  Müller C Year  2018
Journal  Elife Volume  7
PubMed ID  29708496 Mgi Jnum  J:264186
Mgi Id  MGI:6191831 Doi  10.7554/eLife.34985
Citation  Muller C, et al. (2018) Reduced expression of C/EBPbeta-LIP extends health and lifespan in mice. Elife 7:e34985
abstractText  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/EBPbeta-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/EBPbeta-LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice. Moreover, female C/EBPbeta(DeltauORF) mice display an extended lifespan. Since LIP levels increase upon aging in wild type mice, our data reveal an important role for C/EBPbeta in the aging process and suggest that restriction of LIP expression sustains health and fitness. Thus, therapeutic strategies targeting C/EBPbeta-LIP may offer new possibilities to treat age-related diseases and to prolong healthspan.
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