Research Paper Volume 10, Issue 5 pp 1027—1052
Common and unique transcriptional responses to dietary restriction and loss of insulin receptor substrate 1 (IRS1) in mice
- 1 Institute des Sciences de la Vie, Faculty of Sciences, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
- 2 The Breast Cancer Now Toby Robins Research Centre The Institute of Cancer Research, London, UK
- 3 Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
- 4 Glasgow Molecular Pathology Node, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
- 5 Glasgow Polyomics, Wolfson Wohl Cancer Research Centre, University of Glasgow, Garscube Campus, Bearsden, UK
- 6 Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
- 7 MRC London Institute of Medical Sciences, London, UK
- 8 Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK
- 9 Glasgow Ageing Research Network (GARNER), Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
- 10 Present address: Cerevance, Cambridge Science Park, Cambridge, UK
received: February 1, 2018 ; accepted: May 8, 2018 ; published: May 20, 2018 ;https://doi.org/10.18632/aging.101446
How to Cite
Copyright: Page et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.