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Series GSE81959 Query DataSets for GSE81959
Status Public on Jun 27, 2016
Title Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary Calorie restriction (CR) is the most robust non-genetic intervention to universally delay the onset of age-related diseases and extend mean and maximum lifespan. However, species, strain, sex, diet, age of onset, and level of CR are emerging as important variables to consider for a successful CR response. Here, we investigated the role of strain, sex and level of CR on outcomes of health and survival in mice. Response to CR varied from lifespan extension to no effect on survival, while consistently delaying the onset and impact of diseases independently of strain, sex and level of dietary restriction. CR led to transcriptional and metabolomics changes in the liver indicating anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. Additionally, CR prevented the age-associated decline in the proteostasis network. Further, CR increased mitochondrial number and preserved their ultrastructure and function with age. Abrogation of mitochondrial function by deletion of fumarate hydratase or malate dehydrogenase 2 negated the life-prolonging effects of CR in yeast and worms. In F1 hybrid strains of mice, the lifespan response to CR tracked with the dam, indicating that the mitochondrial haplotype is an important regulator of CR. Our data illustrate the complexity of the CR responses within a single animal species in the context of aging, with a clear separation of outcomes related to health and survival, highlighting the complexities of translation of CR into human interventions.
 
Overall design The study examines the effects of sex (male/female), mouse strain (DBA2/J versus C57BL/J), and diet (Ad libitum, 20% caloric restriction (20%CR), or 40%CR) using six biological replicate samples per group.
 
Contributor(s) Mitchell SJ, Matute JM, Scheibye-Knudsen M, Fang E, Aon M, Gonzalez JA, Cortassa S, Kaushik S, Gonzalez-Freire M, Wahl D, Ali A, Calvo-Rubio M, Burón MI, Guiterrez V, Ward TM, Palacios HH, Cai H, Frederick D, Hine C, Broeskamp F, Habering L, Dawson J, Beasley TM, Wan J, Ikeno Y, Hubbard G, Becker K, Zhang Y, Bohr V, Longo D, Navas P, Ferrucci L, Sinclair D, Cohen P, Egan J, Mitchell JR, Baur JA, Allison DB, Villalba JM, Madeo F, Cuervo AM, Pearson KJ, Ingram D, Bernier M, de Cabo R
Citation(s) 27304509
Submission date May 26, 2016
Last update date Jun 22, 2020
Contact name Supriyo De
Organization name NIA-IRP, NIH
Department Laboratory of Genetics and Genomics
Lab Computational Biology & Genomics Core
Street address 251 Bayview Blvd
City Baltimore
State/province Maryland
ZIP/Postal code 21224
Country USA
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (72)
GSM2178579 DBA_liver_Female_ AL_replicate_1
GSM2178580 DBA_liver_Female_ AL_replicate_2
GSM2178581 DBA_liver_Female_ AL_replicate_3
Relations
BioProject PRJNA323500

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE81959_Non-normalized_data.txt.gz 6.4 Mb (ftp)(http) TXT
GSE81959_RAW.tar 3.1 Mb (http)(custom) TAR
Processed data included within Sample table

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