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Abstract
Most animals alternate periods of feeding with periods of fasting often coinciding
with sleep. Upon >24 hr of fasting, humans, rodents, and other mammals enter alternative
metabolic phases, which rely less on glucose and more on ketone body-like carbon sources.
Both intermittent and periodic fasting result in benefits ranging from the prevention
to the enhanced treatment of diseases. Similarly, time-restricted feeding (TRF), in
which food consumption is restricted to certain hours of the day, allows the daily
fasting period to last >12 hr, thus imparting pleiotropic benefits. Understanding
the mechanistic link between nutrients and the fasting benefits is leading to the
identification of fasting-mimicking diets (FMDs) that achieve changes similar to those
caused by fasting. Given the pleiotropic and sustained benefits of TRF and FMDs, both
basic science and translational research are warranted to develop fasting-associated
interventions into feasible, effective, and inexpensive treatments with the potential
to improve healthspan.