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

Title: Common and unique transcriptional responses to dietary restriction and loss of insulin receptor substrate 1 (IRS1) in mice
Authors: Page, MM
Schuster, EF
Mudaliar, M
Herzyk, P
Withers, DJ
Selman, C
Item Type: Journal Article
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.
Issue Date: 20-May-2018
Date of Acceptance: 8-May-2018
URI: http://hdl.handle.net/10044/1/60609
DOI: https://dx.doi.org/10.18632/aging.101446
ISSN: 1945-4589
Publisher: Impact Journals
Start Page: 1027
End Page: 1052
Journal / Book Title: Aging
Volume: 10
Issue: 5
Copyright Statement: © Page et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0 - https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Wellcome Trust
Medical Research Council
Funder's Grant Number: 511377
MC-A654-5QB40
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Geriatrics & Gerontology
insulin/IGF-1 signalling
dietary restriction
insulin receptor substrate 1
transcriptomics
lifespan
LIFE-SPAN EXTENSION
LONG-LIVED MICE
TERM CALORIC RESTRICTION
GENE-EXPRESSION
CAENORHABDITIS-ELEGANS
C-ELEGANS
METHIONINE RESTRICTION
INHIBIT TRANSLATION
MODEL ORGANISMS
SKELETAL-MUSCLE
Developmental Biology
Publication Status: Published
Online Publication Date: 2018-05-20
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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