(P22-038-25) Effects of Time-Restricted Feeding on Liver and Muscle Metabolism in Aging

Objectives: Time-restricted feeding (TRF) has been researched as a safe approach to promoting longevity and improving health expectancy. In addition, TRF contributes to preserving cell survival and stimulating regeneration markers. However, there are clinical concerns that TRF might lead to muscle mass loss, given that the post-prandial stage promotes signaling for muscle protein synthesis. This concern is particularly significant for the elderly, who physiologically lose muscle mass as they age. Therefore, the objective was to evaluate the effects of time-restricted feeding on hepatic metabolism and muscle mass.

Methods: C57BL/6J mice were divided into three groups: young (6 months), old (24 months), and old-TRF. The TRF involved feeding for 12 hours during their active cycle and fasting for 12 hours during the light cycle for 8 weeks. Analysis of physiological, histological, and molecular parameters, and publicly available RNA sequencing data were performed.

Results: The caloric and protein intake of the older animals did not differ from that of the aged TRF group. Old and old-TRF mice showed increased glucose tolerance and insulin sensitivity compared to the young mice, these results do not seem to be related to changes in body fat. Our findings indicate that older animals showed an increase in inflammatory markers and collagen fibres in the liver, but did not show fat accumulation. In contrast, old-TRF mice showed reductions in inflammation and collagen fibres, along with a lower protein content of Notch1 in the liver. The old groups had lower muscle mass than the young group However, aged TRF mice showed no difference in muscle mass compared to aged mice. The transcriptomic analysis supports our findings that aging is associated with the activation of the Notch1 pathway and shows the role of the circadian cycle in regulating inflammation.

Conclusions: The TRF can enhance metabolism in older mice without affecting their muscle mass.

Funding Sources: FAPESP 2020/15679-2; FAPESP 2024/06644-1.