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J Gerontol A Biol Sci Med Sci. 2009 Jul;64(7):711-22. doi: 10.1093/gerona/glp051. Epub 2009 May 4.

Life-span extension in mice by preweaning food restriction and by methionine restriction in middle age.

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  • 1Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, 48109-2200, USA.

Abstract

Life span can be extended in rodents by restricting food availability (caloric restriction [CR]) or by providing food low in methionine (Meth-R). Here, we show that a period of food restriction limited to the first 20 days of life, via a 50% enlargement of litter size, shows extended median and maximal life span relative to mice from normal sized litters and that a Meth-R diet initiated at 12 months of age also significantly increases longevity. Furthermore, mice exposed to a CR diet show changes in liver messenger RNA patterns, in phosphorylation of Erk, Jnk2, and p38 kinases, and in phosphorylation of mammalian target of rapamycin and its substrate 4EBP1, HE-binding protein 1 that are not observed in liver from age-matched Meth-R mice. These results introduce new protocols that can increase maximal life span and suggest that the spectrum of metabolic changes induced by low-calorie and low-methionine diets may differ in instructive ways.

PMID:
19414512
PMCID:
PMC2691799
DOI:
10.1093/gerona/glp051
[PubMed - indexed for MEDLINE]
Free PMC Article
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