Genetic variation in the murine lifespan response to dietary restriction: From life extension to life shortening

Chen Yu Liao, Brad A. Rikke, Thomas E. Johnson, Vivian Diaz, James F Nelson

Research output: Contribution to journalArticle

262 Citations (Scopus)

Abstract

Chronic dietary restriction (DR) is considered among the most robust life-extending interventions, but several reports indicate that DR does not always extend and may even shorten lifespan in some genotypes. An unbiased genetic screen of the lifespan response to DR has been lacking. Here, we measured the effect of one commonly used level of DR (40% reduction in food intake) on mean lifespan of virgin males and females in 41 recombinant inbred strains of mice. Mean strain-specific lifespan varied two to threefold under ad libitum (AL) feeding and 6- to 10-fold under DR, in males and females respectively. Notably, DR shortened lifespan in more strains than those in which it lengthened life. Food intake and female fertility varied markedly among strains under AL feeding, but neither predicted DR survival: therefore, strains in which DR shortened lifespan did not have low food intake or poor reproductive potential. Finally, strain-specific lifespans under DR and AL feeding were not correlated, indicating that the genetic determinants of lifespan under these two conditions differ. These results demonstrate that the lifespan response to a single level of DR exhibits wide variation amenable to genetic analysis. They also show that DR can shorten lifespan in inbred mice. Although strains with shortened lifespan under 40% DR may not respond negatively under less stringent DR, the results raise the possibility that life extension by DR may not be universal.

Original languageEnglish (US)
Pages (from-to)92-95
Number of pages4
JournalAging Cell
Volume9
Issue number1
DOIs
StatePublished - Feb 2010

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Life Expectancy
Eating
Inbred Strains Mice
Fertility
Genotype

Keywords

  • Calorie restriction
  • Food restriction
  • Lifespan
  • Longevity
  • Nutrition

ASJC Scopus subject areas

  • Cell Biology
  • Aging

Cite this

Genetic variation in the murine lifespan response to dietary restriction : From life extension to life shortening. / Liao, Chen Yu; Rikke, Brad A.; Johnson, Thomas E.; Diaz, Vivian; Nelson, James F.

In: Aging Cell, Vol. 9, No. 1, 02.2010, p. 92-95.

Research output: Contribution to journalArticle

Liao, Chen Yu ; Rikke, Brad A. ; Johnson, Thomas E. ; Diaz, Vivian ; Nelson, James F. / Genetic variation in the murine lifespan response to dietary restriction : From life extension to life shortening. In: Aging Cell. 2010 ; Vol. 9, No. 1. pp. 92-95.
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