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

Academic Article

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 agematched 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. © The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Sun L; Sadighi Akha AA; Miller RA; Harper JM
  • Start Page

  • 711
  • End Page

  • 722
  • Volume

  • 64
  • Issue

  • 7