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)
|
Text
161974.pdf - Published Version Available under License Creative Commons Attribution. 7MB |
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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| 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 |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information