Total Mortality Reduction: How to Calculate Combined Effects

When combining multiple interventions, you cannot simply add their individual mortality reductions because:

  • Mortality risks overlap (e.g., two interventions may target the same biological pathway).
  • Diminishing returns apply (reducing risk further becomes harder as you approach zero).

 

Correct Calculation Method

  1. Convert % reductions to survival multipliers:
  • A 10% reduction = 0.90 multiplier (1 – 0.10).
  • A 20% reduction = 0.80 multiplier.
  1. Multiply the survival probabilities:
  • Example: Two 10% reductions → ( 0.90 \times 0.90 = 0.81 ) (19% total reduction, not 20%).
  1. Adjust for overlap:
  • If interventions share mechanisms (e.g., NMN + Resveratrol both boost NAD+), assume higher overlap (e.g., ( 0.90 \times 0.95 = 0.855 ) → 14.5% reduction).

Applied Example: Top 5 Interventions

Intervention Low ↓Mort High ↓Mort Survival Multiplier (Low) Survival Multiplier (High)
Rapamycin 8% 15% 0.92 0.85
Aerobic Exercise 6% 12% 0.94 0.88
Mediterranean Diet 5% 10% 0.95 0.90
Metformin 5% 12% 0.95 0.88
NMN 4% 10% 0.96 0.90

Combined Low Estimate:
( 0.92 \times 0.94 \times 0.95 \times 0.95 \times 0.96 = 0.747 ) → 25.3% total reduction.

Combined High Estimate:
( 0.85 \times 0.88 \times 0.90 \times 0.88 \times 0.90 = 0.533 ) → 46.7% total reduction.

Realistic Adjusted Estimate: ~30–40% (accounting for pathway overlaps).

Key Rules

  1. Non-overlapping mechanisms (e.g., Rapamycin + Exercise) compound more additively.
  2. Overlapping mechanisms (e.g., NMN + Resveratrol) compound less additively.
  3. Upper limit: Even with 10+ interventions, total reduction rarely exceeds 50–60% in practice.

Practical Implications

  • Prioritize interventions with distinct mechanisms:
  • Rapamycin (mTOR) + Metformin (AMPK) + Exercise (CR mimic) → Higher combined effect.
  • Avoid stacking similar supplements:
  • NMN + Resveratrol → Partial overlap (both boost NAD+/sirtuins).