TY - JOUR TI - Reduced expression of C/EBPβ-LIP extends health and lifespan in mice AU - Müller, Christine AU - Zidek, Laura M AU - Ackermann, Tobias AU - de Jong, Tristan AU - Liu, Peng AU - Kliche, Verena AU - Zaini, Mohamad Amr AU - Kortman, Gertrud AU - Harkema, Liesbeth AU - Verbeek, Dineke S AU - Tuckermann, Jan P AU - von Maltzahn, Julia AU - de Bruin, Alain AU - Guryev, Victor AU - Wang, Zhao-Qi AU - Calkhoven, Cornelis F A2 - Sonenberg, Nahum VL - 7 PY - 2018 DA - 2018/04/30 SP - e34985 C1 - eLife 2018;7:e34985 DO - 10.7554/eLife.34985 UR - https://doi.org/10.7554/eLife.34985 AB - 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. KW - C/EBPβ KW - lifespan KW - ageing KW - longevity KW - mTORC1 KW - calorie restriction JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -