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Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice
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A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and

Sebastian Brandhorst1, In Young Choi1, Min Wei1

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Cell Metabolism
|June 23, 2015
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Summary

Alternating prolonged fasting (PF) and nutrient-rich diets extend yeast lifespan. In mice and humans, fasting-mimicking diets (FMDs) promote regeneration, longevity, and reduce aging-related disease risk factors, enhancing healthspan.

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Area of Science:

  • Gerontology and Regenerative Medicine

Background:

  • Prolonged fasting (PF) enhances stress resistance, but its impact on longevity remains unclear.
  • Understanding the effects of fasting interventions on aging and healthspan is crucial for developing strategies to promote longevity.

Purpose of the Study:

  • To investigate the effects of fasting-mimicking diets (FMDs) on lifespan, regeneration, and age-related disease biomarkers.
  • To evaluate the potential of FMDs as an intervention to promote healthspan and longevity.

Main Methods:

  • Yeast lifespan was assessed with alternating PF and nutrient-rich medium.
  • Mice underwent bi-monthly cycles of a 4-day FMD, followed by refeeding.
  • Physiological parameters, stem cell levels, regeneration, disease incidence, and cognitive function were measured in mice.
  • A pilot clinical trial assessed the effects of three FMD cycles on aging biomarkers.

Main Results:

  • Alternating PF extended yeast lifespan independently of known longevity genes.
  • FMD cycles in mice reduced organ size, increased progenitor/stem cells, promoted regeneration, extended longevity, decreased visceral fat, lowered cancer incidence, rejuvenated the immune system, and retarded bone loss.
  • In old mice, FMDs enhanced neurogenesis, lowered IGF-1 and PKA, elevated NeuroD1, and improved cognition.
  • Pilot trial showed FMD cycles reduced risk factors for aging, diabetes, cardiovascular disease, and cancer.

Conclusions:

  • Fasting-mimicking diets (FMDs) promote regeneration and extend lifespan in model organisms.
  • FMDs show potential for improving healthspan and reducing age-related disease risk in humans.
  • FMDs represent a promising intervention for promoting longevity and healthy aging.