Autophagy

Autophagy is a catabolic cellular process activated by stress that Ray Peat viewed as a double-edged survival mechanism, not an unqualified good. 2 Peat defined it as the activation of lysosomal enzymes to degrade damaged proteins into amino acids for reuse, a process that occurs steadily under normal conditions but becomes drastic under duress. 2 He argued that autophagy is triggered by glucose deprivation, hypoxia, heavy metal poisoning, lipid peroxidation, and irradiation, allowing individual cells to survive at the expense of the organism's organized function. 2 When prolonged, this defensive state leads to loss of tissue function, fibrosis, or cancerization, as cells prioritize their own survival without regard to the whole. 2

Peat detailed the biochemical cascade linking stress to autophagy, centering on the enzyme heme oxygenase. 1 Stress induces heme oxygenase to produce carbon monoxide (CO), which, alongside estrogen, prevents apoptosis and promotes autophagy for short-term survival. 1 The accumulation of polyunsaturated fats (PUFA) with aging amplifies this reaction, as their peroxidation produces toxins including CO, and stress-induced prostaglandin E2 further activates heme oxygenase and aromatase, increasing estrogen synthesis. 1 Peat emphasized that the cholinergic nervous system, active during the night, also activates heme oxygenase, meaning even normal cyclic stress can, when combined with continuous low-level harmful factors, create systemic inflammation and fibrosis. 1

Peat explicitly cautioned against the popularization of autophagy induction, particularly through fasting. 2 He stated that while autophagy is part of normal cell turnover, drastically intensifying it can prepare cells for either destruction or cancerization, and he advised against drugs known to amplify the process because some also promote tumor survival. 2 Georgi Dinkov extended this critique, citing evidence that autophagy is a strong tumor promoter in a majority of cancers, with autophagy-inhibiting drugs now in clinical trials. 6 Dinkov noted that fasting initially slows tumor growth but subsequently makes tumors highly aggressive and resistant to therapy. 6 He characterized autophagy as an ancient evolutionary mechanism, akin to parathyroid hormone and serotonin, whose upregulation is generally undesirable. 4

Dinkov and Danny Roddy have argued that the benefits of fasting-induced autophagy are misrepresented, as the process is simply a recycling of raw materials during starvation, accompanied by damaging events like fatty acid release, stress system activation, and lipid peroxidation. 2 They highlighted that thyroid hormone (T3), fructose, glucose, and trehalose can also increase autophagy, undermining the claim that fasting is the sole or optimal trigger. 2 Roddy summarized the perspective by stating that the body's stress response during fasting, including autophagy, is a sign of damage being framed as useful, a concept tied to a disrupted redox balance that promotes proliferation without serving the organism's overall health. 8