Autophagy appears to be tumor-suppressive during the early stages of tumorigenesis and tumor-promoting at later stages.
In this review, we discuss the role of basal autophagy in maintaining homeostasis, in part through the maintenance of stem cell populations and the prevention of cellular senescence. We also consider how stress-induced senescence, for example during oncogene activation and in premalignant disease, might rely on autophagy, and the possibility that the age-associated decline in autophagy might promote tumor development through a variety of mechanisms. Ultimately, evidence suggests that autophagy is required for malignant cancer progression in a number of settings. Thus, autophagy appears to be tumor-suppressive during the early stages of tumorigenesis and tumor-promoting at later stages.
Intermittent fasting activates markers of autophagy in mouse liver, but not muscle from mouse or humans. In humans, autophagy markers in muscle were reduced, likely in response to weight loss.
Super interesting that they have done a study on humans and autophagy but if I understand the conclusion right than they could not see any increase in autophagy during fasting?
The paper above is on flies.
As far as I know, there is no regular blood assay to measure human autophagy, and it’s probably highly tissue specific. Although this lab is working on it for humans (2021)
Measurement of autophagic flux in humans: an optimized method for blood samples
“Preclinical studies have demonstrated that reductions in autophagic flux cause cancer and exacerbate chronic diseases, including heart disease and the pathological hallmarks of dementia. Autophagic flux can be increased by targeting nutrition-related biochemical signaling. To date, translation of this knowledge has been hampered because there has been no way to directly measure autophagic flux in humans. In this study we detail a method whereby human macroautophagic/autophagic flux can be directly measured from human blood samples”
Valter Longo has done a lot of work on fasting and autophagy.
Fasting and Caloric Restriction in Cancer Prevention and Treatment
“Starving mice or mammalian cells triggers autophagy in various tissues, which is regulated
by several genes that also regulate aging and stress resistance, such as AMPK, mTOR, and sirtuins. Oncogenic signaling, e.g., through PI3K and Akt, has been shown to inhibit autophagy, whereas tumor suppressors such as PTEN and TSC2 can trigger autophagy. Autophagy is elevated in many cancer cells and increases the resistance of cancer cells to chemotherapy. Increased autophagy has been hypothesized to be mediated by ammonia as a by-product of glutaminolysis occurring in the mitochondria of malignant cells undergoing the Warburg effect to supply biosynthetic precursors required for their high proliferation rate. Therefore, autophagy triggered by fasting may be beneficial to normal cells but detrimental to malignant cells.”
CR is by far, the most robust lifespan extension intervention (ie. by delaying cancer) in mice…autophagy?
I meant this paper on mice and human
Intermittent fasting activates markers of autophagy in mouse liver, but not muscle from mouse or humans
We examined the effect of IF on markers of autophagy in liver and skeletal muscle in mice and in humans.
I think I read somewhere (Longo?) that humans don’t enter any appreciable autophagy until many days into a fast, say 5+.
There are many guesses in the field but when autophagy is optimized and on what frequency nobody knows. If we are frustrated regarding what dose regime is optimal when it comes to rapamycin than we will be much more frustrated when it comes to extended fasting. Science in the extended fasting field is not even close to what it is when it comes to rapamycin.
But most people see autophagy more as a dimmer than a on-off-switch. Its always on even in a anabolic state but in low doses. Some day we will ger more data in the topic. I thought the new study I refered to above was one step foward in the area but I don’t understand the conclusion regarding humans. Do you understand it and can explain it?
I haven’t found full access to the paper. Now that you mention it, I did reach out to one of the authors, general autophagy extension question in humans.
His response: “Autophagy process is complex but not proven in humans”
In the future, when we reach out to the authors (anyone here who does this) lets also ask for a PDF copy of the paper, they usually give it out to anyone who asks, and then we can post it here to share.
I normally do, and I did ask, noting now he didn’t provide. Will circle back and share.