Abstract Body (Do not enter title and authors here): Background: Time-restricted feeding (TRF) is an effective strategy for anti-aging management yet its prophylactic/therapeutic applicability against cardiac aging is unknown.
Methods: To assess the effects of TRF on cardiac aging, male mice were randomized into the normal diet+ad libitum feeding (N-ALF), normal diet+TRF (N-TRF), high-fat diet+ALF (H-ALF), high-fat diet+TRF (H-TRF). Metagenomic sequencing was used to investigate the diversity, composition, and evolution of the gut microbiota. The metabolomics was employed to investigate the impact of TRF on the metabolic profile of feces. Using fecal microbiota transplantation, TRF has been validated to delay cardiac aging by optimizing gut microbial composition and function.
Results: Compared to the H-ALF group, the H-TRF group showed that the expression of senescence markers p53 and p21 was reduced. In addition, the myocardial interstitial collagen deposition and the expression of collagen I and III were reduced by TRF. Moreover, TRF reduced left ventricular posterior wall dimensions at end-diastole, interventricular septal thickness at end-diastole, and myocardial diastolic function index E/e' in mice. These suggested that TRF delays high-fat diet-induced cardiac aging. Compared with the H-ALF group, the TRF group exhibited an increase in the alpha diversity of gut microbiota. At the phylum level, the abundance of the Bacteroides was increased by TRF. At the genus level, the abundance of Bacteroides, Parabacteroides, and Akkermansia was increased by TRF. There were 11 characteristic strains in the H-TRF group, six of these strains are closely related to the production of short-chain fatty acids (SCFAs). Function prediction of the differential genes showed an increase in the SCFAs pathway in the H-TRF. LC-MS profiling of feces showed that TRF can reduce the levels of l-tyrosine, l-tryptophan, phenylalanine, valine, indoxyl-sulfate, cholesterol-sulfate, and tetradecanedioic acid in the intestines from high-fat diet mice. TRF increased the levels of 16-oxo-heptadecanoic acid, propionic acid, butyric acid, 2-methylpropionic acid, acetoacetate, succinate, and acetoacetyl-CoA. Using the mice with HFD, those that received gut microbiota from H-TRF showed decreased levels of cardiac senescence markers. It was suggested that gut microbiota plays a crucial role in TRF improving cardiac aging.
Conclusions: TRF improves high-fat diet-induced cardiac aging by optimizing the composition and function of gut microbiota.