Long-term feeding of a high-fat diet ameliorated age-related phenotypes in SAMP8 mice

Abstract

High-fat diets (HFD) have been thought to increase the risk of obesity and metabolic syndrome, as well as shorten lifespan. On the other hand, chrono-nutritional studies have shown that time-restricted feeding during active phase significantly suppresses the induction of HFDinduced obesity in mouse model. However, the long-term effects of time-restricted HFD feeding on aging are unknown. Therefore, in this study, we set up a total of four groups: mutual combination of ad libitum feeding or night-time-restricted feeding (NtRF) and an HFD or a control diet. We examined their long-term effects in a senescence-accelerated mouse strain, SAMP8, for over a year. Hearing ability, cognitive function, and other behavioral and physiological indexes were evaluated during the study. Unexpectedly, SAMP8 mice did not show early onset of death caused by the prolonged HFD intake, and both HFD and NtRF retarded age-related hearing loss (AHL). NtRF improved grip strength and cognitive memory scores, while HFD weakly suppressed age-related worsening of the appearance scores associated with the eyes. Notably, the HFD also retarded the progression of AHL in both DBA/2J and C57BL/6J mice. These results suggest that HFD prevents aging unless metabolic disorders occur and that HFD and NtRF are independently effective in retarding aging; thus, the combination of HFD and chrono-nutritional feeding may be an effective anti-aging strategy.