Dataset Information

Reduced expression of C/EBP?-LIP extends health and lifespan in mice.

ABSTRACT: 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/EBP?-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/EBP?-LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice. Moreover, female C/EBP??uORF mice display an extended lifespan. Since LIP levels increase upon aging in wild type mice, our data reveal an important role for C/EBP? in the aging process and suggest that restriction of LIP expression sustains health and fitness. Thus, therapeutic strategies targeting C/EBP?-LIP may offer new possibilities to treat age-related diseases and to prolong healthspan.

SUBMITTER: Muller C

PROVIDER: S-EPMC5986274 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Müller Christine C Zidek Laura M LM Ackermann Tobias T de Jong Tristan T Liu Peng P Kliche Verena V Zaini Mohamad Amr MA Kortman Gertrud G Harkema Liesbeth L Verbeek Dineke S DS Tuckermann Jan P JP von Maltzahn Julia J de Bruin Alain A Guryev Victor V Wang Zhao-Qi ZQ Calkhoven Cornelis F CF

eLife 20180604

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 <i>Cebpb</ ...[more]

PMID: 29708496

Similar Datasets

Project description:The prevention or delay of the onset of age-related diseases prolongs survival and improves quality of life while reducing the burden on the health care system. Activation of sirtuin 1 (SIRT1), an NAD+ deacetylase, improves metabolism and confers protection against physiological and cognitive disturbances in old age. SRT1720 is a specific SIRT1 activator that has health and lifespan benefits in adult mice fed a highfat diet. We found extension in lifespan, delayed onset of age-related metabolic diseases, and improved general health in mice fed a standard diet after SRT1720 supplementation. Inhibition of pro-inflammatory gene expression both in the liver and muscle of SRT1720-treated animals was noted. SRT1720 lowered phosphorylation of NF-κB pathway regulators in vitro only when SIRT1 was functionally present. Combined with our previous work, the current study further supports the beneficial effects of SRT1720 on health across the lifespan in mice. Groups of 28 week old male C57BL/6J mice were maintained on ad libitum AIN-93G SD diet, or an ad libitum AIN-93G diet supplemented with SRT1720 for the rest of their lives. SRT1720 was added at a dose of 1.33 g drug per kg of chow, formulated to provide daily doses of approximately 100 mg drug per kg bodyweight to the mice. 5 mice from each group were selected and RNA was extracted from both muscle and liver tissue using 1.0mm glass beads in a Precellys 24 Tissue Homogenizer and Qiagen RNeasy Mini Kits for Fibrous Tissue according to manufacturer's specifications. Quality and quantity of the total RNA was checked with the Agilent 2100 bioanalyzer using RNA 6000 Nano chips. RNA samples were labeled using the Illumina TotalPrep RNA Amplification Kit. In short, 0.5ug of total RNA was first converted into single-stranded cDNA with reverse transcriptase using an oligo-dT primer containing the T7 RNA polymerase promoter site and then copied to produce double-stranded cDNA molecules. The double stranded cDNA was cleaned and concentrated with the supplied columns and used in an overnight in-vitro transcription reaction where single-stranded RNA (cRNA) was generated and labeled by incorporation of biotin-16-UTP. Arrays were hybridized using a total of 0.75ug of biotin-labeled cRNA at 58 degrees C for 16 hours to Illumina's Sentrix MouseRef-8 v2 Expression BeadChips. Each BeadChip has ~24,000 well-annotated RefSeq transcripts with approximately 30-fold redundancy. The arrays were washed, blocked and the biotin labeled cRNA was detected by staining with streptavidin-Cy3. Arrays were scanned at a resolution of 0.8um using the Beadstation 500 X from Illumina and the data was extracted using the Illumina GenomeStudio software(v1.6.0). Any spots at or below the background were filtered out using an Illumina detection p value of 0.02 and above. The natural log of all remaining scores were used to find the avg and std of each array and the z-score normalization was calculated and presented below. Z-score = (raw value - avg)/std.

Dataset Information

Reduced expression of C/EBP?-LIP extends health and lifespan in mice.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets