Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice

  • Sarah J. Mitchell (Contributor)
  • Morten Scheibye-Knudsen (Contributor)
  • Evandro Fang (Contributor)
  • Miguel Aon (Contributor)
  • Sonia Cortassa (Contributor)
  • Susmita Kaushik (Contributor)
  • Marta Gonzalez-Freire (Contributor)
  • Devin Wahl (Contributor)
  • Ahmed Ali (Contributor)
  • Miguel Calvo-Rubio (Contributor)
  • María I. Burón (Contributor)
  • Vincent Guiterrez (Contributor)
  • Theresa M. Ward (Contributor)
  • Hector H. Palacios (Contributor)
  • Huan Cai (Contributor)
  • David W. Frederick (Contributor)
  • Christopher Hine (Contributor)
  • Filomena Broeskamp (Contributor)
  • Lukas Habering (Contributor)
  • John Dawson (Contributor)
  • T. Mark Beasley (Contributor)
  • Junxiang Wan (Contributor)
  • Yuji Ikeno (Contributor)
  • Gene Hubbard (Contributor)
  • Kevin Becker (Contributor)
  • Yongqing Zhang (Contributor)
  • Vilhelma Bohr (Contributor)
  • D. L. Longo (Contributor)
  • Placido Navas (Contributor)
  • L. Ferrucci (Contributor)
  • David Sinclair (Contributor)
  • Pinchas Cohen (Contributor)
  • Josephine M. Egan (Contributor)
  • James R. Mitchell (Contributor)
  • Joseph A. Baur (Contributor)
  • David B. Allison (Contributor)
  • José M. Villalba (Contributor)
  • Frank Madeo (Contributor)
  • Ana Maria Cuervo (Contributor)
  • Kevin J. Pearson (Contributor)
  • Donald K. Ingram (Contributor)
  • Michel Bernier (Contributor)
  • Rafael De Cabo (Contributor)

Dataset

Description

Accession Number: GSE81959

Platform:
GPL6885: Illumina MouseRef-8 v2.0 expression beadchip

Organism: Mus musculus

Published on 2016-06-27

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.

Contact:
Name: Kevin G Becker
Organization: National Institute on Aging, NIH
Laboratory: Gene Expression and Genomics Unit
Deparment: Laboratory of Genetics
Address: 251 Bayview Blvd Baltimore MD 21224 USA
Email: beckerk@grc.nia.nih.gov
Phone: 410-558-8360

Organization: Illumina Inc.
Address: 9885 Towne Centre Drive San Diego CA 92121 USA
Email: expression@illumina.com, techsupport@illumina.com
Phone: 1 800 809 4566
Web-Link: www.illumina.com
Date made availableMay 26 2016
PublisherGene Expression Omnibus

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