title: Dietary calorie restriction in the Emory mouse: effects on lifespan, eye lens cataract prevalence and progression, levels of ascorbate, glutathione, glucose, and glycohemoglobin, tail collagen breaktime, DNA and RNA oxidation, skin integrity, fecundity, and cancer.
abstract: The Emory mouse is the best model for age-related cataract. In this work we compare the effects of feeding a control diet (C) with a diet restricted (R) by 40% relative to C animals. In the R animals, median lifespan was extended by 40%. The proportion of R mice with advanced cataract was lower than C mice as early as 5 months of age. The mean grade of cataract was lower in R animals, beginning at 11 months and continuing until the end of the study. Ascorbate levels in R plasma and liver were 41-56% of C animals. There was no difference between diet groups with respect to lens ascorbate. Aging was associated with a decrease in ascorbate in lenses and kidneys in C and R mice. By 22 months, R animals had 48% higher liver glutathione levels than C mice. Liver glutathione levels were maximal at 12 months. Plasma glucose levels were > 27% lower in R animals at 6.5 and 22 months, and there was a 14% increase in glucose levels upon aging for both diet groups. In R mice, glycohemoglobin levels were 51% lower and tail collagen breaktime was decreased by 40%, even in younger animals. Collagen breaktime increased > 360% upon aging for both diet groups. Rates of production of urinary oxo8dG and oxo8G were higher in R animals compared with C animals, and increased upon aging. C animals exhibited more cancer and dermatological lesions, but less tail tip necrosis and inflamed genitals than R mice. These data allow evaluation of several theories of aging.
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
authors.forename: A
authors.initials: A
authors.lastname: Taylor
authors.forename: R D
authors.initials: RD
authors.lastname: Lipman
authors.forename: J
authors.initials: J
authors.lastname: Jahngen-Hodge
authors.forename: V
authors.initials: V
authors.lastname: Palmer
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.forename: N
authors.initials: N
authors.lastname: Padhye
authors.forename: G E
authors.initials: GE
authors.lastname: Dallal
authors.forename: D E
authors.initials: DE
authors.lastname: Cyr
authors.forename: E
authors.initials: E
authors.lastname: Laxman
authors.forename: D
authors.initials: D
authors.lastname: Shepard
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002386:Cataract / Q000453:epidemiology* / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D002149:Energy Intake; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D008136:Longevity; D051379:Mice; D008815:Mice, Inbred Strains; D010084:Oxidation-Reduction; D015995:Prevalence; D012313:RNA / Q000378:metabolism; D012867:Skin / Q000473:pathology; D013623:Tail / Q000378:metabolism
chemical_list: D001205:Ascorbic Acid; D003094:Collagen; D004247:DNA; D005947:Glucose; D005978:Glutathione; D006442:Glycated Hemoglobin; D012313:RNA