The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access originally published online on May 4, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2009 64A(7):711-722; doi:10.1093/gerona/glp051
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Life-Span Extension in Mice by Preweaning Food Restriction and by Methionine Restriction in Middle Age
1 Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor
2 Geriatric Research Education and Clinical Center, Ann Arbor VA Medical Center, Michigan
Address correspondence to Dr James Harper, PhD, Department of Biology, University of Michigan, Room 3005, BSRB, Box 2200, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200. Email: jmharper{at}umich.edu
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Abstract |
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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.
Keywords Methionine; Litter size; Caloric restriction; TOR; ERK
Received: November 6, 2008; Accepted: March 13, 2009