Mid-life onset of dietary restriction extends life and prolongs cognitive functioning.

Fourteen-month-old C57BL/6 (NIA) mice were placed on a nutritionally complete diet providing 139.4 kcal/week. Over a 2-month period the food ration of experimental mice (AE) was reduced to 85 kcal/week, where it remained for the duration of the study. An aged control group (AC) continued with the higher calorie diet. At age 22 months, AC mice and half of the AE mice (AE22) were given a battery of behavioral tests. The remaining AE mice (AE25) were given the test battery at age 25 months. Also, a middle-aged control group (MC) was tested at age 13 months. Midlife onset caloric restriction (CR) increased longevity and preserved strength, coordination, and spontaneous alternation behavior, and altered responses to enclosed alleys. A spatial discrimination in the Morris water maze and a spatial delayed matching-to-sample water-escape task were insensitive to age and diet. The aged mice were adversely affected by testing.