Colin Selman, Nicola D. Kerrison, Anisha Cooray, Matthew D. W. Piper, Steven J. Lingard, Richard H. Barton, Eugene F. Schuster, Eric Blanc, David Gems, Jeremy K. Nicholson, Janet M. Thornton, Linda Partridge and Dominic J. Withers Physiol Genomics 27:187-200, 2006. First published Aug 1, 2006; doi:10.1152/physiolgenomics.00084.2006 You might find this additional information useful... Supplemental material for this article can be found at: http://physiolgenomics.physiology.org/cgi/content/full/00084.2006/DC1 This article cites 64 articles, 31 of which you can access free at: http://physiolgenomics.physiology.org/cgi/content/full/27/3/187#BIBL This article has been cited by 3 other HighWire hosted articles: Gene expression profiling of the short-term adaptive response to acute caloric restriction in liver and adipose tissues of pigs differing in feed efficiency S. Lkhagvadorj, L. Qu, W. Cai, O. P. Couture, C. R. Barb, G. J. Hausman, D. Nettleton, L. L. Downloaded from Anderson, J. C. M. Dekkers and C. K. Tuggle Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2010; 298 (2): R494-R507. [Abstract] [Full Text] [PDF] Comment on "Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis" C. Selman, S. Lingard, D. Gems, L. Partridge and D. J. Withers Science, May 23, 2008; 320 (5879): 1012b-1012b. [Abstract] [Full Text] [PDF] physiolgenomics.physiology.org Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice C. Selman, S. Lingard, A. I. Choudhury, R. L. Batterham, M. Claret, M. Clements, F. Ramadani, K. Okkenhaug, E. Schuster, E. Blanc, M. D. Piper, H. Al-Qassab, J. R. Speakman, D. Carmignac, I. C. A. Robinson, J. M. Thornton, D. Gems, L. Partridge and D. J. Withers FASEB J, March 1, 2008; 22 (3): 807-818. [Abstract] [Full Text] [PDF] Updated information and services including high-resolution figures, can be found at: http://physiolgenomics.physiology.org/cgi/content/full/27/3/187 on February 15, 2010 Additional material and information about Physiological Genomics can be found at: http://www.the-aps.org/publications/pg This information is current as of February 15, 2010 . Physiological Genomics publishes results of a wide variety of studies from human and from informative model systems with techniques linking genes and pathways to physiology, from prokaryotes to eukaryotes. It is published quarterly in January, April, July, and October by the American Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright © 2005 by the American Physiological Society. ISSN: 1094-8341, ESSN: 1531-2267. Visit our website at http://www.the-aps.org/. Physiol Genomics 27: 187–200, 2006. First published August 1, 2006; doi:10.1152/physiolgenomics.00084.2006. CALL FOR PAPERS Comparative Genomics Coordinated multitissue transcriptional and plasma metabonomic profiles following acute caloric restriction in mice Colin Selman,1* Nicola D. Kerrison,2* Anisha Cooray,3 Matthew D. W. Piper,4 Steven J. Lingard,1 Richard H. Barton,3 Eugene F. Schuster,2 Eric Blanc,2 David Gems,4 Jeremy K. Nicholson,3 Janet M. Thornton,2 Linda Partridge,4 and Dominic J. Withers1 1Centre for Diabetes and Endocrinology, Department of Medicine, University College London, Rayne Institute, London; 2European Molecular Biology Laboratory (EMBL)-European Bioinformatics Institute (EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge; 3Biological Chemistry Section, Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College London, South Kensington, London; and 4UCL Centre for Ageing Research, Department of Biology, University College London, London, United Kingdom Downloaded from Submitted 10 May 2006; accepted in final form 28 July 2006 Selman, Colin, Nicola D. Kerrison, Anisha Cooray, Matthew D. W. of vertebrate and invertebrate species (24, 41, 46, 61). How- Piper, Steven J. Lingard, Richard H. Barton, Eugene F. Schuster, Eric ever, the mechanisms through which CR extends life span are Blanc, David Gems, Jeremy K. Nicholson, Janet M. Thornton, Linda not understood. CR is accompanied by changes in gene and Partridge, and Dominic J. Withers. Coordinated multitissue transcriptional protein expression and resultant alterations in both cellular and physiolgenomics.physiology.org and plasma metabonomic profiles following acute caloric restriction in mice. Physiol Genomics 27: 187–200, 2006. First published August 1, 2006; whole organism metabolism that are thought to underlie its doi:10.1152/physiolgenomics.00084.2006.—Caloric restriction (CR) in- effects on aging. creases healthy life span in a range of organisms. The underlying mecha- RNA transcript profiles have been useful for defining nisms are not understood but appear to include changes in gene expression, changes in gene expression following CR, leading to the protein function, and metabolism. Recent studies demonstrate that acute CR formulation of experimentally testable hypotheses. Long-term alters mortality rates within days in flies. Multitissue transcriptional changes CR in rodents attenuates many age-associated transcriptional and concomitant metabolic responses to acute CR have not been described. changes, including expression of genes involved with cellular We generated whole genome RNA transcript profiles in liver, skeletal stress, in skeletal muscle (36), hypothalamus (20), and liver muscle, colon, and hypothalamus and simultaneously measured plasma (11, 16). However, to date, most microarray mRNA expression metabolites using proton nuclear magnetic resonance in mice subjected to acute CR. Liver and muscle showed increased gene expressions associated studies in mice have been confined to single tissues and have with fatty acid metabolism and a reduction in those involved in hepatic lipid profiled only part of the genome. In addition, single-tissue on February 15, 2010 biosynthesis. Glucogenic amino acids increased in plasma, and gene expres- studies have varied widely in experimental design, bioinfor- sion for hepatic gluconeogenesis was enhanced. Increased expression of matic analysis, and mouse strains used (29), thus making direct genes for hormone-mediated signaling and decreased expression of genes comparisons between tissues difficult. Furthermore, altered involved in protein binding and development occurred in hypothalamus. Cell transcript profiles have not been related to concomitant plasma proliferation genes were decreased and cellular transport genes increased in metabolic changes. colon. Acute CR captured many, but not all, hepatic transcriptional changes Changes in gene expression following initiation of CR (or of long-term CR. Our findings demonstrate a clear transcriptional response across multiple tissues during acute CR, with congruent plasma metabolite dietary restriction; DR) appear rapid in both Drosophila and changes. Liver and muscle switched gene expression away from energeti- mice. Significant shifts in transcript profile in Drosophila cally expensive biosynthetic processes toward energy conservation and uti- occurred within 3 days following DR (47). In studies of hepatic lization processes, including fatty acid metabolism and gluconeogenesis. gene expression in mice, a rapid and cumulative shift mirroring Both muscle and colon switched gene expression away from cellular prolif- a long-term (12 mo) CR transcriptional profile was observed eration. Mice undergoing acute CR rapidly adopt many transcriptional and after 2, 4, or 8 wk of CR. A return to ad libitum (AD) levels metabolic changes of long-term CR, suggesting that the beneficial effects of reversed 90% of this long-term CR profile after 8 wk (16). This CR may require only a short-term reduction in caloric intake. suggests that these changes in gene expression during acute CR aging; microarray; gene expression may induce rapid beneficial effects on life span. In Drosophila, a dietary shift to DR altered mortality rate within days (40). However, accurate measurements of mortality rates during CALORIC RESTRICTION (CR) extends mean and maximum life acute CR have not been measured in mice, although CR span and retards various age-associated pathologies in a range initiated at 12 mo of age extended mean and maximum life span, decreased age-associated mortality, and reduced cancer * C. Selman and N. D. Kerrison contributed equally to this work. incidence (16, 49). Article published online before print. See web site for date of publication In this study, we examined acute whole genome transcrip- (http://physiolgenomics.physiology.org). tional changes following short-term CR in liver, skeletal mus- Address for reprint requests and other correspondence: C. Selman, Centre for Diabetes and Endocrinology, Dept. of Medicine, Univ. College London, cle, hypothalamus, and colon of 16-wk-old male C57BL/6 Rayne Institute, 5 University St., London WC1E 6JJ, UK (e-mail: c.selman@ mice subjected to a stepwise 16-day protocol of CR terminat- ucl.ac.uk). ing in a 48-h period of 30% CR (see supplemental data; 1094-8341/06 $8.00 Copyright © 2006 the American Physiological Society 187 188 MULTITISSUE TRANSCRIPTIONAL AND METABOLITE RESPONSE TO ACUTE CALORIC RESTRICTION Supplemental Materials are available in the online version of portion of the upper colon were removed, flash-frozen in liquid this article). In parallel, we employed a nuclear magnetic nitrogen, and stored at Ϫ80°C until RNA extraction. To minimize the resonance (NMR) metabonomic strategy capable of identifying potential for hierarchies