Long-term fasting: Multi-system adaptations in humans (GENESIS) study-A single-arm interventional trial

Area of Science:

• Metabolic and signaling pathways
• Human physiology
• Nutritional science

Background:

• Fasting impacts metabolic pathways, influencing lifespan in animal models.
• Human fasting metabolism relies on various metabolites, but organ contributions and tissue remodeling are not fully understood.
• Changes in organ volume and composition during fasting require further exploration.

Purpose of the Study:

• To investigate the multi-systemic effects of long-term fasting (LF) and food reintroduction in humans.
• To analyze changes in body composition, organ volume, lipid metabolism, protein utilization, blood metabolites, and gut microbiome.
• To provide a comprehensive understanding of tissue remodeling processes during fasting and refeeding.

Main Methods:

• Prospective, single-arm trial with 100 subjects undergoing 9±3 day fasting periods (250 kcal/day).
• Assessment of organ and bone composition, blood lipid profiles, HDL transport, PBMC metabolomics, protein persulfidation, and gut microbiome.
• Detailed analysis using MRI and spectroscopy for 32 subjects, with follow-up examinations at 1 and 4 months.

Main Results:

• Fasting induces significant changes in body composition and organ volumes.
• Metabolic profiles, including blood lipids and gut microbiome, are substantially altered.
• Tissue remodeling and metabolic adaptations occur during fasting and subsequent refeeding.

Conclusions:

• Long-term fasting profoundly impacts human physiology, affecting body composition and organ function.
• Understanding these systemic changes is crucial for optimizing health and longevity interventions.
• This study provides novel insights into the complex adaptations to fasting and refeeding in humans.