TL;DR: A large-scale mouse study (n=960) found that both fasting and calorie restriction (CR) extended lifespan, with 40% CR showing the most dramatic results (36% increase in median lifespan). The 40% CR group also maintained youthful physical activity levels throughout life. Key biomarkers like lymphocyte count and red blood cell distribution width (RDW) strongly predicted lifespan in both mice and humans.
Study Design and Groups (n=192 mice per group)
- Ad libitum (control): Unrestricted feeding
- 1-day fast/week: Wednesday noon to Thursday noon
- 2-day fast/week: Wednesday noon to Friday noon
- 20% CR: Actually achieved 27.1% reduction
- 40% CR: Actually achieved 44% reduction
Key Findings
1. Lifespan Effects
- 1-day fast: Extended lifespan despite 2.5% higher total food intake (p=0.06)
- 2-day fast: Same lifespan extension as 1-day fast, despite 11.5% lower food intake
- 20% CR: Further increased median lifespan
- 40% CR: Largest effect, 36% increase in median lifespan
2. Physical Activity
- All groups except 40% CR showed age-related decline in wheel running
- 40% CR maintained youthful activity levels throughout life
- All groups had similar baseline activity at 5 months
3. Biomarker Correlations with Lifespan
Strongest Positive Correlator
- High lymphocyte counts at 16 months
Strongest Negative Correlator
- High RDW (red blood cell distribution width) at 10 months
Human Translation
The findings align with human studies:
Lymphocytes
- Optimal level: ~2,000 cells/µL
- Higher counts associate with lower mortality risk
- Levels naturally decline with age
RDW
- Optimal range: 11.4-12.5%
- Values >13.7% associate with increased mortality risk
- Exception: Very low values (<11.4%, rare) also increase risk
- RDW increases with age
This comprehensive study suggests that maintaining youthful biomarker levels might be key to maximizing lifespan, with both fasting and calorie restriction showing promise as interventions.
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