Calorie restriction and dwarf mice in gerontological research.
What aging process is delayed by calorie restriction (CR) and mutations that produce long-lived dwarf mice? From 1935 until 1996, CR was the only option for increasing the maximum lifespan of laboratory rodents. In 1996, the mutation producing the Ames dwarf mouse (Prop-1(-/-)) was reported to increase lifespan. Since 1996, other gene mutations that cause dwarfism or lower body weight have been reported to increase the lifespan of mice. The recent discovery of long-lived mutant dwarf mice provides an opportunity to investigate common features between CR and dwarf models. Both CR and dwarf mutations increase insulin sensitivity. Elevated insulin sensitivity reduces oxidative stress, a potential cause of aging. The elevation of liver insulin sensitivity by the hormone adiponectin in CR and long-lived dwarf mice can lower endogenous glucose production and raise fatty acid oxidation. Adiponectin reduction of plasma glucose in CR and long-lived dwarf mice can thereby lower age-related increases in oxidative damage and cancer.
McKee Alderman
J
J
Department of Nutrition, School of Medicine, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599-7461, USA.
DePetrillo
Michael A
MA
Gluesenkamp
Angela M
AM
Hartley
Antonia C
AC
Verhoff
S Veronica
SV
Zavodni
Katherine L
KL
Combs
Terry P
TP
D052242:Adiponectin / Q000502:physiology; D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D031204:Caloric Restriction; D004392:Dwarfism / Q000235:genetics; D004435:Eating; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D013006:Growth Hormone / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance; D008136:Longevity / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D023421:Models, Animal; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D009765:Obesity / Q000503:physiopathology; D018384:Oxidative Stress; D005082:Physical Exertion
D052242:Adiponectin; D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein; D013006:Growth Hormone; D005947:Glucose