Abstract
Dietary restriction (DR) is an important experimental paradigm for lifespan and healthspan extension, but its specific contribution regarding the type, onset, and duration are still debatable. This study was designed to examine the impact of different dietary protocols by assessing the behavioral changes during aging. We exposed male Wistar rats of various age to ad libitum (AL) or DR (60 per cent of AL daily intake) feeding regimens with different onsets. The impact of DR on locomotor activity, memory, and learning was examined in 12-, 18-, and 24-month-old treated animals and controls using open field and Y-maze tests. We have also evaluated the effects of different DR's through the quantification of animal frailty, using behavioral data to create the frailty score. Our results indicated that DR improves general animal activity and spatial memory and decreases frailty with the effect being highly dependent on DR duration and onset. Notably, life-long restriction started at young age had the most profound effect. In contrast, shorter duration and later onset of restricted diet had significantly lower or no impact on animal's behavior and frailty. This study signifies the importance of DR starting point and duration as critical determinants of DR effects on healthspan.