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.
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.
Taylor
A
A
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Lipman
R D
RD
Jahngen-Hodge
J
J
Palmer
V
V
Smith
D
D
Padhye
N
N
Dallal
G E
GE
Cyr
D E
DE
Laxman
E
E
Shepard
D
D
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
D001205:Ascorbic Acid; D003094:Collagen; D004247:DNA; D005947:Glucose; D005978:Glutathione; D006442:Glycated Hemoglobin; D012313:RNA