Common and unique transcriptional responses to dietary restriction and loss of insulin receptor substrate 1 (IRS1) in mice.
Loading...
Embargo End Date
ICR Authors
Authors
Page, MM
Schuster, EF
Mudaliar, M
Herzyk, P
Withers, DJ
Selman, C
Schuster, EF
Mudaliar, M
Herzyk, P
Withers, DJ
Selman, C
Document Type
Journal Article
Date
2018-05-20
Date Accepted
2018-05-08
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.
Citation
Aging, 2018, 10 (5), pp. 1027 - 1052
Source Title
Publisher
IMPACT JOURNALS LLC
ISSN
1945-4589
eISSN
1945-4589
Collections
Research Team
Endocrine Therapy Resistance