Common and unique transcriptional responses to dietary restriction and loss of insulin receptor substrate 1 (IRS1) in mice

Page, M. M., Schuster, E. F., Mudaliar, M. , Herzyk, P. , Withers, D. J. and Selman, C. (2018) Common and unique transcriptional responses to dietary restriction and loss of insulin receptor substrate 1 (IRS1) in mice. Aging, 10(5), pp. 1027-1052. (doi: 10.18632/aging.101446) (PMID:29779018) (PMCID:PMC5990393)

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Abstract

Dietary restriction (DR) is the most widely studied non-genetic intervention capable of extending lifespan across multiple taxa. Modulation of genes, primarily within the insulin/insulin-like growth factor signalling (IIS) and the mechanistic target of rapamycin (mTOR) signalling pathways also act to extend lifespan in model organisms. For example, mice lacking insulin receptor substrate-1 (IRS1) are long-lived and protected against several age-associated pathologies. However, it remains unclear how these particular interventions act mechanistically to produce their beneficial effects. Here, we investigated transcriptional responses in wild-type and IRS1 null mice fed an ad libitum diet (WTAL and KOAL) or fed a 30% DR diet (WTDR or KODR). Using an RNAseq approach we noted a high correlation coefficient of differentially expressed genes existed within the same tissue across WTDR and KOAL mice and many metabolic features were shared between these mice. Overall, we report that significant overlap exists in the tissue-specific transcriptional response between long-lived DR mice and IRS1 null mice. However, there was evidence of disconnect between transcriptional signatures and certain phenotypic measures between KOAL and KODR, in that additive effects on body mass were observed but at the transcriptional level DR induced a unique set of genes in these already long-lived mice.

Item Type:Articles
Additional Information:This work was supported through a BBSRC New Investigator Grant (reference BB/H012850/2) and startup funds from University of Glasgow (College of Medicine, Veterinary and Life Sciences) to CS and a Welcome Trust Strategic Award (reference 098565/Z/12/Z) to DJW.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Selman, Professor Colin and Mudaliar, Dr Manikhandan and Herzyk, Dr Pawel
Authors: Page, M. M., Schuster, E. F., Mudaliar, M., Herzyk, P., Withers, D. J., and Selman, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Aging
Publisher:Impact Journals
ISSN:1945-4589
ISSN (Online):1945-4589
Published Online:20 May 2018
Copyright Holders:Copyright © 2018 Page et al.
First Published:First published in Aging 10(5):1027-1052
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
638451Dissecting the mechanisms underlying lifespan extension in insulin signalling mutant miceColin SelmanBiotechnology and Biological Sciences Research Council (BBSRC)BB/H012850/2RI BIODIVERSITY ANIMAL HEALTH & COMPMED