Imperial College London
Professor Dominic Withers

ProfessorDominicWithers

Faculty of Medicine, Institute of Clinical Sciences

Clinical Chair in Diabetes & Endocrinology
 
 
 
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Contact

 

d.withers

 
 
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Location

 

Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Page:2018:10.18632/aging.101446,
author = {Page, MM and Schuster, EF and Mudaliar, M and Herzyk, P and Withers, DJ and Selman, C},
doi = {10.18632/aging.101446},
journal = {Aging},
pages = {1027--1052},
title = {Common and unique transcriptional responses to dietary restriction and loss of insulin receptor substrate 1 (IRS1) in mice},
url = {http://dx.doi.org/10.18632/aging.101446},
volume = {10},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Page,MM
AU  - Schuster,EF
AU  - Mudaliar,M
AU  - Herzyk,P
AU  - Withers,DJ
AU  - Selman,C
DO  - 10.18632/aging.101446
EP  - 1052
PY  - 2018///
SN  - 1945-4589
SP  - 1027
TI  - Common and unique transcriptional responses to dietary restriction and loss of insulin receptor substrate 1 (IRS1) in mice
T2  - Aging
UR  - http://dx.doi.org/10.18632/aging.101446
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000433605000015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/60609
VL  - 10
ER  -
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