What food restriction does to autophagy in the brain, as measured in mice.
What the evidence says
- Every timing figure here is from mice: the study food-restricted mice ”for 24 or 48 hours” and measured autophagy in their neurons[1]
- After 24 hours of food restriction, cortical neurons showed a marked increase in the number and size of autophagosomes in the cell body, with the signal in the neurites rising more than three-fold — (p = 0.004, data not shown), the paper’s own parenthesis[1]
- After 48 hours, the cell-body changes were ”even more dramatic” — while the neurite signal ”diminished to resting levels”. The divergence is between compartments of the same neuron, not between cell types: cell body climbing, neurites returning to rest[1]
- Purkinje cells showed a ∼4-fold increase in autophagosome number (p < 0.0002, Student's t test), with autophagosome diameter rising from about 0.2 µm in normal-fed animals to 0.5 µm at 48 hours[1]
- The mechanism is mTOR suppression: food restriction sharply reduced phosphorylated S6 ribosomal protein in Purkinje cell bodies — fasting lowers mTOR activity and releases the brake on autophagy. The rise came from increased production, not reduced clearance[1]
- A review of fasting in mice argues that ”overnight fasting of mice is not comparable with overnight fasting of humans because the mouse has a nocturnal circadian rhythm and a higher metabolic rate”; mice ”consume two-thirds of their total food intake during the night”, and the review suggests that fasting begun at different points in the circadian rhythm produces different results[2]
- Earlier work had failed to detect brain autophagy even after 48 hours of restriction, and the brain was assumed a ”metabolically privileged site” exempt from it. This study overturned that and gave the first in vivo demonstration of autophagosomes in cortical neurons of normal-fed mammals — basal neuronal autophagy exists without any fasting at all[1]