Chronic Caloric Restriction Improves Locomotor Activity in Aging Female Mice

Abstract

Caloric restriction (CR) is the most widely studied model of longevity. Aging induces alterations in behavior and reduced locomotion, i.e., bradykinesis, is a reliable biomarker of aging. CR, applied for a relatively short time (weeks to months) has been shown to improve bradykinesis, but it is not known what happens when the animals advance to old age. In order to explore the behavioral effects linked to long term CR and aging, we examined the behavior study of old (>24mo) female mice under CR since youth, with mice monitored for the same time on normal diets (ND). Average body weights fell over 2 years for CR mice (19 to 16g) and, as expected, increased for ND mice (18 to 25g). Beginning at 10 weeks of age, mice were fed either a normal diet (ND (equivalent to 10% CR)) or 40% CR and monitored up to 24 months of age. We used an open field cage system to store, replay, and analyze locomotor activity expressed as socially interactive or motile behavior. The mice under chronic CR displayed hyper‐activity (social and motile behaviors) as compared to ND mice. While comparing ND vs. 40% CR mice respectively, we detected an increase in stereotypy episodes (188 ± 13 to 458 ± 106 counts, P<0.05), movement time (658 ± 83 to 1559 ± 348 sec, P<0.05), and decrease in rest time (6540 ± 83 to 5637 ± 348 sec, P<0.05). These results suggest that increased locomotor activity is not only an early feature of CR, but persists with aging. This may not only be a biomarker for longevity, but also may be involved in the mechanism of longevity induced by CR.