Intermittent fasting’s astonishing effect on Health, Aging, and Disease, our top 5 takeaways

Written By Tina O

“Effects of Intermittent Fasting on Health, Aging, and Disease”   

 Written by Rafael de Cabo, Ph.D., and Mark P. Mattson, Ph.D and published in the prestigious New England Journal of Medicine.


  • Intermittent Fasting (IF) and stress resistance have significant effects on health and aging 


  • This article explains the brilliant process of Metabolic Switching and shows a lot of the benefits are from this switch and not just the caloric restriction! 


  • Cells and organ systems adapt to the challenge of the metabolic switch by activating signaling pathways that bolster mitochondrial function, stress resistance, and antioxidant defenses while up-regulating autophagy to remove damaged molecules and recycle their components.


  • During the period of energy restriction, cells adopt a stress-resistance mode through the reduction in insulin signaling and overall protein synthesis. 

  • Ketone bodies are not just fuel used during periods of fasting; they are potent signaling molecules with major effects on cell and organ functions.Ketone bodies regulate the expression and activity of many proteins and molecules”



“In one of the earliest studies of intermittent fasting, Goodrick and colleagues reported that the average life span of rats is increased by up to 80% when they are maintained on a regimen of alternate-day feeding, started when they are young adults”

  • In humans, the three most widely studied intermittent-fasting regimens are:
    • Alternate-day fasting,
    • 5:2 intermittent fasting (fasting 2 days each week), and
    • Daily time-restricted feeding.
  • Personally I am happy 5:2 is listed as I feel much more effect of the metabolic switch , HgH , energy as well a mental sharpness compared to daily time-restricted eating .
intermittent fasting's effect on health, aging, and disease
  • This chart shows Cellular Responses to Energy Restriction That Integrate Cycles of Feeding and Fasting with Metabolism. 
  • During fasting, cells activate pathways that enhance intrinsic defenses  against oxidative and metabolic stress and   These same pathways  remove or repair damaged molecules (Fig. 1).5 During the feeding period, cells engage in tissue-specific processes of growth and plasticity. 
  • To me  “tissue-specific “ is an exciting term and shows our bodies innate ability to heal the area of our body, organs, brain, which is needed most at a particular time . It seems it will take many more years for scientists to uncover all the fascinating healing our bodies are capable of.
  • During the Recovery/Refeeding  Phase: There is increased protein synthesis, mitochondrial biogenesis, cell growth and plasticity as well as structural and functional tissue remodeling. This suggests that after a fast proper refeeding and recovery are important.


Periodic flipping of the metabolic switch not only provides the ketones that are necessary to fuel cells during the fasting period but also elicits highly orchestrated systemic and cellular responses that carry over into the fed state to bolster mental and physical performance, as well as disease resistance.

intermittent fasting health, aging, and disease
      • This chart shows metabolic adaptations to IF in various organs. One thing that particularly stood to me was the discussion of free fatty acids resulting in the release of fibroblast growth factors. 
      • Very in-depth explanation of what happens once FFAs(Free Fatty Acids) are released into the blood stream:
      • FFAs(Free Fatty Acids)  released into the circulation are transported into hepatocytes, where they produce the ketone bodies acetoacetate and β-hydroxybutyrate (β-HB). FFAs also activate the transcription factors peroxisome proliferator–activated receptor α (PPAR-α) and activating transcription factor 4 (ATF4), resulting in the production and release of fibroblast growth factor.
      • The liver converts fatty acids to ketone bodies, which provide a major source of energy for many tissuesESPECIALLY to the brain, during fasting. 
        • ( Katherine please show chart )Figure 2 (page 3)
        • This chart shows metabolic adaptations to IF in various organs. One thing that particularly stood to me was the discussion of free fatty acids resulting in the release of fibroblast growth factors. 
        • Very in-depth explanation of what happens once FFAs(Free Fatty Acids) are released into the blood stream:
Intermittent Fasting, Brain, Health, Aging, and Disease
  • Here we can see what happens during Intermittent Fasting, Recovery /Refeeding, as well as long term adaptions.
    • During the Recovery/Refeeding  phase: Increased protein synthesis, increased mitochondrial biogenesis, cell growth and plasticity structural and functional tissue remodeling.
    • And, again, this shows after a fast the proper refeeding and recovery is important!
  • Clinical Applications – This section briefly reviews examples of findings from studies of preclinical animal models of disease as well as patients of varying diseases. The diseases covered are:  Obesity and Diabetes Mellitus, Cardiovascular DiseaseCancerNeurodegenerative Disorders, AsthmaMultiple SclerosisArthritisSurgical and Ischemic Tissue Injury.


Notes On Fast Mimicking Molecules:

“Studies of the mechanisms of caloric restriction and intermittent fasting in animal models have led to the development and testing of pharmacologic interventions that mimic the health and disease-modifying benefits of intermittent fasting. Examples include agents that impose a mild metabolic challenge (2-deoxyglucose, metformin, and mitochondrial-uncoupling agents), bolster mitochondrial bioenergetics (ketone ester or nicotinamide riboside), or inhibit the mTOR pathway (sirolimus). However, the available data from animal models suggest that the safety and efficacy of such pharmacologic approaches are likely to be inferior to those of intermittent fasting” (For now at least, it looks like we are still gonna have to fast if we want all the benefits.)

Which part of the article did you find most interesting?

You can check out the full article by clicking here!

Here are some other fasting resources you might be interested in:

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