02 Dec 2021 Ep. 76: Why Caloric Restriction Is NOT Responsible For Lifespan Extension (Hormesis Part 2)

Posted at 04:45h in Podcast by

Listen to the podcast on Apple Podcasts | Google Podcasts | Stitcher| Spotify

In this episode we discuss:

  • How the largest body of evidence cited in favor of hormesis actually doesn’t support it at all
  • Why caloric restriction is NOT responsible for slowing aging and extending lifespan (and what is actually responsible) 
  • The many factors that confound the calorie restriction research (including differences between organisms, poor research design, amino acid restriction, PUFA, endotoxin, and more) 

3:36 – the physiology of hormesis and the general support for hormesis 

12:54 – outlining the problems with hormesis 

18:51 – how differences between organisms confound the caloric restriction research 

37:34 – the problem with using proxy markers to evaluate health effects and the importance of context 

48:20 – how differences between organisms confound the caloric restriction research (cont.) 

51:58 – how hydration status and macronutrient ratios confound the caloric restriction research 

55:57 – how the myopic hormetic view leads to the ignorance of many confounding variables 

1:02:00 – how the restriction of particular amino acids, ad libitum feeding, and a refined diet confound the caloric restriction research 

1:11:58 – how PUFA confounds the caloric restriction research 

1:30:09  – how endotoxin and gut health confound the caloric restriction research 

Links from this episode

  • Life extension in C. elegans longevity research occurs due to a hibernation-type state called dauer which is not representative of a slowing of aging or improvement in health (1)  

  • Low-carb diets mimic starvation (1, 2) 

  • Ep. 47: A Critique of The ROS Theory of Obesity (The Croissant Diet Part 1) (podcast episode)
  • Ep. 48: A Critique of The SCD1 Theory of Obesity (The Croissant Diet Part 2) (podcast episode)
  • Ep. 23: How to Slow Aging Part 1: Increasing Your Metabolism And Competing Theories (podcast episode)
  • Ep. 24: How to Slow Aging Part 2: Problems With Caloric Restriction and What To Do Instead (podcast episode)
  • Metabolic poisons extend lifespan in C. elegans (1)
  • Ep. 58: Altitude, Panic Attacks, Swelling, Heart Failure... (Oxygenation, Swelling, & pH Balance 3) (podcast episode)

  • Metformin inhibits efficient mitochondrial respiration (1, 2) 

  • Metformin causes lactic acidosis (1, 2) 

  • Metformin decreases intestinal permeability and has antimicrobial effects (1, 2, 3) 

  • Fasting causes decreases in thyroid hormones and androgens while increasing cortisol (1, 2, 3, 4, 5) 

  • Yeast exhibit lifespan extension in response to reduced glucose availability due to an increase in metabolic rate and efficiency, which is the opposite effect of most organisms (1)
  • Yeast grow in an undifferentiated way when starved of glucose or other nutrients, similar to cancer cells (1, 2, 3)
  • Drosophila and other fruit flies exhibit increased longevity due to increased hydration and reduced protein to carbohydrate ratios, not caloric restriction (1)

  • Monkeys fed whole-food diets did not experience lifespan extension from calorie restriction whereas monkeys fed diets containing sucrose and corn oil did (1) 

  • Amino acid restriction (particularly methionine) accounts for the effects of calorie restriction (1, 2, 3, 4) 

  • Glycine supplementation mimics the lifespan extension exhibited by methionine restriction (1) 

  • Weight gain due to ad libitum feeding accounts for the shorter lifespan in non-calorically-restricted rodents (1)
  • Mice that were calorically restricted and fed more highly unsaturated fats exhibited less lifespan extension than mice that were calorically restricted and fed less unsaturated fats (1)
  • The life-extending effect of caloric restriction is primarily due to its reduction in membrane unsaturation (1)
  • The benefits of caloric restriction can be attributed to alterations in the gut microbiota and reductions in endotoxin (1)
  • Akkermansia muciniphila exerts its benefits by reducing endotoxin exposure and is increased in response to fasting (1, 2)
No Comments

Leave a Comment

This site uses Akismet to reduce spam. Learn how your comment data is processed.