We've been told to eat more heart-healthy foods like olive oil, but the latest nutritional advice is focusing on not just what we eat, but when we eat. Lifestyle changes like intermittent fasting (IF)—which limits eating to specific times of the day—are emerging as promising strategies to boost heart health, but protect against heart disease and peripheral vascular diseases such as atherosclerosis.
“Cardiovascular diseases (CVDs) represent the foremost cause of mortality in our society,” said Jayantha Gunaratne, a Senior Principal Investigator at A*STAR’s Institute of Molecular and Cell Biology (IMCB) and lead of the Translational Biomedical Proteomics lab.
While IF has been shown to lower CVD risk factors in both animals and humans, its molecular effects on heart cells were unclear. To solve this puzzle, Gunaratne teamed up with Thiruma Arumugam from Australia's La Trobe University to lead a multinational, multi-institutional effort to map out the molecular and cellular changes in the hearts of mice following different IF regimens.
Using quantitative mass spectrometry, the researchers tracked the heart proteins of mice undergoing fasting periods of 12-16 hours and every other day (EOD) fasting, and compared them to mice with unrestricted access to food. They also used RNA sequencing to identify any subtle changes in gene expression.
A comprehensive analysis of the data revealed which proteins and genes were most affected by the fasting regimens. They followed up with additional experiments to validate how these changes impacted heart function.
Gunaratne’s team found that IF modified key biological pathways involved in metabolism, cell signalling and epigenetic remodelling. These changes were more significant during longer fasting periods, such as the 16-hour and EOD regimens. The functional studies also showed that IF improved how the heart handled stress compared to the control group.
This study not only supports the view that IF is good for heart health but also provides the most detailed look yet at the molecular changes it triggers in heart cells, according to Gunaratne.
“The findings expose pivotal molecular hubs corrected during IF, opening avenues for developing new medications to address various CVD issues,” said Gunaratne.
Moving forward, the two research groups remain in collaboration to explore how to target the therapeutic opportunities uncovered in this research.
“We’re also focusing on a comprehensive study of IF's impact on the molecular rewiring of vital organs such as the brain, liver and kidneys, as well as its implications for various diseases,” Gunaratne added.
The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology (IMCB).
