Genetic dissection of dietary restriction in mice supports the metabolic efficiency model of life extension
Language: 
English
Abstract: 

Dietary restriction (DR) has been used for decades to retard aging in rodents, but its mechanism of action remains an enigma. A principal roadblock has been that DR affects many different processes, making it difficult to distinguish cause and effect. To address this problem, we applied a quantitative genetics approach utilizing the ILSXISS series of mouse recombinant inbred strains. Across 42 strains, mean female lifespan ranged from 380 to 1070days on DR (fed 60% of ad libitum [AL]) and from 490 to 1020days on an AL diet. Longevity under DR and AL is under genetic control, showing 34% and 36% heritability, respectively. There was no correlation between lifespans on DR and AL; thus different genes modulate longevity under the two regimens. DR lifespans are significantly correlated with female fertility after return to an AL diet after various periods of DR (R=0.44, P=0.006). We assessed fuel efficiency (FE, ability to maintain growth and body weight independent of absolute food intake) using a multivariate approach and found it to be correlated with longevity and female fertility, suggesting possible causality. We found several quantitative trait loci responsible for these traits, mapping to chromosomes 7, 9, and 15. We present a metabolic model in which the anti-aging effects of DR are consistent with the ability to efficiently utilize dietary resources.

Author(s): 
Rikke, Brad A.
Liao, Chen-Yu
McQueen, Matthew B.
Nelson, James F.
Johnson, Thomas E.
Item Type: 
Journal Article
Publication Title: 
Experimental Gerontology
Journal Abbreviation: 
Exp. Gerontol.
Publication Date: 
2010-09
Publication Year: 
2010
Pages: 
691-701
Volume: 
45
Issue: 
9
ISSN: 
1873-6815
DOI: 
10.1016/j.exger.2010.04.008
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 20452416 PMCID: PMC2926251

Turabian/Chicago Citation

Brad A. Rikke, Chen-Yu Liao, Matthew B. McQueen, James F. Nelson and Thomas E. Johnson. 2010-09. "Genetic dissection of dietary restriction in mice supports the metabolic efficiency model of life extension." Experimental Gerontology 45: 9: 691-701. 10.1016/j.exger.2010.04.008.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.exger.2010.04.008 | issn = 1873-6815 | volume = 45 | pages = 691-701 | last = Rikke | first = Brad A. | coauthors = Liao, Chen-Yu, McQueen, Matthew B., Nelson, James F., Johnson, Thomas E. | title = Genetic dissection of dietary restriction in mice supports the metabolic efficiency model of life extension | journal = Experimental Gerontology | date = 2010-09 | pmid = | pmc = }} </ref>