Time-restricted feeding reduces inflammatory markers and downregulates JAG1 and NICD protein levels in the liver of aged mice.

Objectives: The present study aimed to assess whether Time-Restricted Feeding (TRF) modulates inflammation and hepatic Notch1 signalling in C57BL/6J-aged mice.

Methods: Adult mice submitted to the ad libitum diet, aged (24 months-old) submitted to the ad libitum diet and, aged-TRF (24 months-old) subjected to the TRF (12 hours fed in the active cycle and 12 hours fasting in the light cycle) for 8 weeks. We investigated metabolic parameters, liver histology, metabolic-dysfunction-associated fatty liver disease activity score, collagen fiber, hepatic mitochondrial respiration, and publicly available liver Rna-seq datasets from human livers in diverse clinical conditions to clarify Notch1 involvement in liver health.

Results: Our results demonstrated that aged mice (24 months old) showed increases in body weight, liver mass, Notch1 intracellular domain (NICD), and inflammatory markers (NFκB and TLR4 protein levels) in the liver when compared to adult animals. On the other hand, aged mice submitted to a TRF protocol showed reductions in inflammation and collagen fibers, which was accompanied by lower protein content of JAGGED1 and NICD in the liver. Furthermore, aged-TRF mice demonstrated increased liver mitochondrial respiration coupled with ATP production compared to the aged groups. Publicly available liver RNA-seq datasets in humans support our findings, indicating the upregulation of NOTCH1 in fibrosis and inflammation development.

Conclusions: TRF can reduce inflammatory markers and protein content of JAGGED1 and NICD in the liver of aged mice, which can contribute to tissue health and cellular longevity.