Autophagy is a natural, highly regulated process that acts as a cellular recycling and cleanup system. The term, which translates to “self-eating,” describes how cells break down and remove damaged components, such as worn-out proteins and organelles. This mechanism occurs constantly at a low level, but it ramps up significantly when the cell is placed under mild stress, such as nutrient deprivation. Many people are exploring fasting as a means to intentionally activate this deep cellular renewal process.
Understanding Autophagy in Dr. Fung’s Framework
Dr. Jason Fung, an advocate for therapeutic fasting, places autophagy within the context of hormonal regulation, moving the focus away from simple calorie restriction. He suggests that constant eating keeps key metabolic signals elevated, which blocks cellular cleanup. Fasting shifts the body’s internal signaling to allow for repair and maintenance.
Fung emphasizes that fasting’s benefit is the fundamental cellular repair triggered by the absence of nutrient intake. When food intake stops, the hormone insulin drops significantly, causing a shift in growth signals. This change provides the necessary signal for cells to begin clearing out accumulated damage.
The Critical Timeline: When Autophagy Begins
The initiation of autophagy is a gradual process dependent on the duration of caloric deprivation, not a single on/off switch. Mild signs of autophagy may begin to appear in some tissues after approximately 12 to 16 hours of fasting. This early stage coincides with the body exhausting its primary glucose stores and shifting toward burning fat for fuel.
For autophagy to become reliably measurable and significant across multiple tissues, a longer fast is required. Experts, including Dr. Fung, point to the 24-hour mark as the point where the process is noticeably underway. At this stage, the body has firmly switched to a fasting metabolism, and cellular cleanup signals are strong enough to achieve noticeable effects.
The most pronounced effect of autophagy often occurs between 24 and 48 hours of fasting. During this window, the body is fully committed to recycling cellular components to generate energy and building blocks. A fast reaching 48 hours is often cited as the point for deep cellular repair, operating at a high intensity, though precise timing varies among individuals.
The Cellular Signals That Flip the Switch
The mechanism that recognizes the absence of nutrients and initiates cellular recycling involves an interplay between key molecular sensors. The primary signal that stops autophagy is the mechanistic Target of Rapamycin (mTOR), which acts as the cell’s master growth switch. mTOR integrates signals from available nutrients, particularly amino acids and glucose, and when these are abundant, mTOR is active, suppressing cleanup to prioritize cell growth and division.
When fasting begins, the decline in nutrients causes the suppression of mTOR, removing the cellular brake pedal. Simultaneously, the energy-sensing enzyme AMP-activated protein kinase (AMPK) becomes activated. AMPK senses low energy levels and acts as a conservation signal, promoting the use of stored energy and activating pathways that support survival.
The activation of AMPK and the suppression of mTOR work in concert to “flip the switch.” The drop in insulin, coupled with a rise in glucagon, signals the body that nutrients are scarce. AMPK directly promotes autophagy by activating specific protein complexes, while mTOR deactivation removes its inhibitory effect, allowing the cell to enter the recycling state.