Lifespan Extension Is Conserved Across Diverse Species
Caloric restriction extends lifespan in yeast, worms, flies, and rodents.
- +30–50%: Yeast lifespan gain (placeholder figure)
- +40%: C. elegans gain (placeholder figure)
- +15–30%: Mouse gain (placeholder figure)
- 20+: Species studied (placeholder figure)
Conserved effect across taxa
Restriction extends lifespan broadly across evolutionarily distant organisms.
Magnitude varies by species
Shorter-lived organisms show larger relative extension than long-lived ones.
mTOR and IGF-1 Signaling Are Suppressed Under Restriction
Reduced nutrient intake downregulates growth-promoting signaling pathways.
- ~40%: mTOR activity drop (placeholder figure)
- ↓: IGF-1 levels (placeholder figure)
- ↑: AMPK activation (placeholder figure)
- ↑: Sirtuin expression (placeholder figure)
mTOR/IGF-1 axis
Growth-signaling pathways shift toward maintenance and repair modes.
AMPK and sirtuin activation
Energy-sensing pathways rise, promoting autophagy and stress resistance.
Lowered Metabolic Rate Reduces Cumulative Oxidative Stress
Restriction slows reactive oxygen species accumulation over the lifespan.
- ↓: ROS output (placeholder figure)
- ↑: Mitochondrial efficiency (placeholder figure)
- ↓: Protein damage markers (placeholder figure)
- ↓: DNA damage rate (placeholder figure)
Reduced ROS production
Lower throughput metabolism generates fewer damaging byproducts.
Slower macromolecular damage accrual
Cumulative cellular damage builds up more slowly over time.
Benefits Plateau and Reverse at Extreme Restriction Levels
Past a threshold, further restriction stops helping and starts harming.
- ~20–30%: Optimal restriction range (placeholder figure)
- >35–40%: Threshold for harm (placeholder figure)
- ↑ risk: Immune function risk (placeholder figure)
- ↑ risk: Muscle mass risk (placeholder figure)
Non-linear dose-response
Extension benefit follows an inverted-U shape rather than a straight line.
Risks of over-restriction
Excess restriction can impair immunity, fertility, and lean mass.
Applying These Findings to Humans Remains Highly Uncertain
Human trials show metabolic benefits but no confirmed lifespan extension yet.
- 2 years: CALERIE trial duration (placeholder figure)
- Limited: Human lifespan data (placeholder figure)
- Mixed: Primate study consensus (placeholder figure)
- Low–Moderate: Confidence level (placeholder figure)
Human trial evidence
Short-term human trials show improved biomarkers, not proven lifespan gains.
Open translational questions
Long human lifespans make direct extension trials impractical to confirm.
Placeholder callout: translation from short-lived models to humans is unresolved.