Dietary restriction in ILSXISS mice is associated with widespread changes in splicing regulatory factor expression levels

Lee, B. P., Mulvey, L., Barr, G., Garratt, J., Goodman, E., Selman, C. and Harries, L. W. (2019) Dietary restriction in ILSXISS mice is associated with widespread changes in splicing regulatory factor expression levels. Experimental Gerontology, 128, 110736. (doi: 10.1016/j.exger.2019.110736) (PMID:31521722)

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Abstract

Dietary restriction (DR) represents one of the most reproducible interventions to extend lifespan and improve health outcomes in a wide range of species, but substantial variability in DR response has been observed, both between and within species. The mechanisms underlying this variation in effect are still not well characterised. Splicing regulatory factors have been implicated in the pathways linked with DR-induced longevity in C. elegans and are associated with lifespan itself in mice and humans. We used qRT-PCR to measure the expression levels of a panel of 20 age- and lifespan-associated splicing regulatory factors in brain, heart and kidney derived from three recombinant inbred strains of mice with variable lifespan responses to short-term (2 months) or long-term (10 months) 40% DR to determine their relationship to DR-induced longevity. We identified 3 patterns of association; i) splicing factors associated with DR alone, ii) splicing factors associated with strain alone or iii) splicing factors associated with both DR and strain. Tissue specific variation was noted in response to short term or long-term DR, with the majority of effects noted in brain following long term DR in the positive responder strain TejJ89. Association in heart and kidney were less evident, and occurred following short term DR. Splicing factors associated with both DR and strain may be mechanistically involved in strain-specific differences in response to DR. We provide here evidence concordant with a role for some splicing factors in the lifespan modulatory effects of DR across different mouse strains and in different tissues.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Selman, Professor Colin
Authors: Lee, B. P., Mulvey, L., Barr, G., Garratt, J., Goodman, E., Selman, C., and Harries, L. W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:Experimental Gerontology
Publisher:Elsevier
ISSN:0531-5565
ISSN (Online):1873-6815
Published Online:12 September 2019
Copyright Holders:Copyright © 2019 Elsevier Inc.
First Published:First published in Experimental Gerontology 128: 110736
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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