While time-restricted eating (eating within an 8-10 hour window each day) is known to improve organ systems, the genomic changes have largely been unknown. A study in @Cell_Metabolism sheds light on the underlying genomic changes. Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals - ScienceDirect Here’s how:
Background: Time-restricted feeding has been shown to have a variety of health benefits, including improved exercise capacity, sleep, blood pressure, and gut health, as well as reduced cancer risk and neurodegenerative disease severity.
The potential health benefits of TRF may be due to its effects on pathways like mTOR, AMPK, Sirtuins, and insulin/IGF1 signaling, which regulate nutrient intake, processing, and gene expression in the body.
One previous study found that alternate-day fasting (consuming all calories in a single day followed by a day of fasting) led to decreased mTOR signaling and increased autophagy in mice. Other studies have also shown increased autophagy in human cells.
In the liver, time-restricted feeding has been shown to upregulate the expression of genes involved in energy metabolism and stress response while downregulating the expression of genes involved in inflammation and fibrosis.
Time-restricted feeding increases the production of enzymes involved in the breakdown of fats and sugars, which can help the liver more effectively metabolize nutrients.
TRF may improve nutrient metabolism in the liver by reducing oxidative stress and inflammation. Oxidative stress and inflammation can impair liver function and disrupt nutrient metabolism, but time-restricted feeding has been shown to reduce these processes
In the brain, time-restricted feeding has been shown to upregulate the expression of genes involved in neurotransmitter synthesis and plasticity while downregulating the expression of genes involved in inflammation and oxidative stress.
The change in gene expression in the brain and the liver are examples of how TRF changes the expression of over 80% of protein-coding genes in a tissue-specific manner. This affects signaling pathways related to nutrient metabolism, cell growth, and proliferation.
The expression of certain genes (i.e., the process by which the information in a gene is used to produce a protein or other molecule) tends to be more rhythmic or periodic when an organism is subjected to a feeding-fasting cycle.
Both external signals (such as those related to feeding and fasting) and internal clock mechanisms (also known as “endogenous clocks”) play a role in regulating this rhythmic gene expression.
There is some evidence to suggest that the duration and timing of fasting may be more important than the number of calories or nutrient composition in imparting health benefits.
TRF may help to separate the processes of breaking down and using nutrients (catabolism) from the processes of building and repairing tissues (anabolism).
This separation, or compartmentalization, can support metabolic flexibility, which is the ability of the body to adapt to different energy demands and efficiently use different sources of fuel.
The potential anti-aging effects of TRF: 1) Improved metabolic health (↑insulin sensitivity). 2. Reduced inflammation 3. Protection against neurodegeneration by reducing toxic proteins. 4. Increased autophagy. 5. Decreased mTOR signaling
These findings on the gene expression changes induced by TRF may be useful in understanding its effects on pre-clinical models of chronic metabolic disorders, neurodegenerative diseases, and cancer. TRF seems to be an important lever that can be utilized for promoting healthspan.