Life-span extension in mice by preweaning food restriction and by methionine restriction in middle age.
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.
Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, 48109-2200, USA.
Liou
L
Sun
Amir A
AA
Sadighi Akha
Richard A
RA
Miller
James M
JM
Harper
D000367:Age Factors; D000375:Aging; D000818:Animals; D031204:Caloric Restriction / Q000379:methods*; D014676:Diet, Vegetarian; D053208:Kaplan-Meier Estimate; D008017:Life Expectancy; D008136:Longevity; D008297:Male; D008715:Methionine / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016016:Proportional Hazards Models
D008715:Methionine