Calorie Restriction versus Cancer, Viewed in Terms of Growth Signaling

The practice of calorie restriction, eating fewer calories while still obtaining sufficient micronutrients, is well demonstrated to reduce cancer risk in animal models, and also appears to improve outcomes in the case of an established cancer. This is similarly the case for practices such as intermittent fasting or fasting mimicking diets, the latter having undergone trials as an adjuvant therapy in human cancer patients. Researchers here review this topic through the lens of nutrient sensing and growth signaling in the body, such as the well studied pathways involving growth hormone and IGF-1. More growth means more DNA damage, and thus a greater risk of developing cancer. Greater growth signaling also aids an established cancer in all of the obvious ways.

Many dietary patterns, including the Western diet, are associated with reduced lifespan and health span and appear to affect cancer incidence by two major hormonal axes/pathways: (1) the growth hormone-IGF-1; (2) the insulin signaling. Higher protein intake increases the release of growth hormone releasing hormone, and consequently growth hormone release from the pituitary gland and IGF-1 release primarily from the liver. High IGF-1 has been associated with elevated incidence of a number of cancers.

Studies in simple organisms and mice, demonstrate the link between nutrients and particularly protein intake, growth factors, DNA damage, and cancer. The effect of growth factors on DNA damage and cancer is mediated, at least in part, by oxidative stress and damage, but in part also by the inhibition of apoptosis. The reduced activity of growth factors and the lowering of oxidation and DNA damage not only decreases cancer but also extends longevity, since aging is the most important factor promoting cancer. Calorie restriction (CR) is a powerful anti-aging intervention, but it also forces the organism into an extremely low nourishment state, which may not constitute malnourishment in the short-term but which may do so long-term.

Interventions such as intermittent fasting (IF) and periodic fasting (PF) are emerging as alternatives to CR, with some of them being able to minimize side effects and burden while maximizing efficacy. Studies on PF have also pointed to 2 key processes absent or low in CR and IF: (a) a pronounced breakdown process both at the intracellular (autophagy etc) and cellular (apoptosis) levels requiring 2 or more days and associated with a high ketogenic state, (b) a rebuilding/regeneration process involving stem cells and progenitor cells in multiple system and associated with the return from PF to normal feeding (re-feeding).

The fasting mimicking diet (FMD) developed and studied by our laboratories is emerging as a viable and effective intervention in the longevity and cancer prevention fields, since it does not require chronic treatment, it does not cause malnourishment or loss of muscle mass and may be effective when performed only a few times a year for 5 days. In the future years it will be important to continue to test different nutritional interventions with the potential to extend the health span and prevent cancer, with a focus on those that are safe and feasible for long-term use in humans.



You could also just not eat IGF-1....right?

Posted by: GREGORY S SCHULTE at October 18th, 2021 1:05 PM

I have been fascinated with Dr. Longo's work for a long time. everyone should also read about his fasting pre-chemotherapy studies. It seems that fasting weakens cancer cells making them more susceptible to treatment. At the same time, healthy cells increase their defenses. So we end up with a therapy that is possibly mote effective and less damaging at the same time.

Posted by: august33 at October 19th, 2021 9:24 PM
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