TL;DR: A 2024 Nature study shows that inhibiting interleukin-11 (IL-11) extends median mouse lifespan by 28.7% when administered at an age equivalent to human late-50s, with improved health markers and reduced tumor incidence. This extension rivals that seen with rapamycin, raising questions about whether IL-11 inhibition works through similar or complementary mechanisms.

Key Findings

Lifespan Extension

• Median lifespan increase: 28.7% average across sexes
  • Females: 25% increase
  • Males: 22.5% increase
• Results achieved through both:
  • Pharmacological inhibition (antibody X203 treatment)
  • Genetic deletion (Il11-/- mice)

Health Improvements vs Control Groups

• Better glucose tolerance
• Lower serum cholesterol
• Lower fat mass
• Greater muscle mass and strength
• Reduced visible tumor incidence
• 100-week-old treated mice showed better health metrics than 75-week-old untreated mice

Mechanism & Scientific Context

IL-11 Background

1. Expression increases with age in:
   • Liver
   • Fat
   • Skeletal muscle
2. Higher expression in centenarians vs middle-aged individuals
3. Associated with cell senescence markers

Signaling Pathways Affected

• JAK-STAT3
• ERK
• mTOR
• Other pathways

Key Scientific Question

Whether IL-11 inhibition’s effects are primarily through:

1. mTOR pathway (making it functionally equivalent to rapamycin)
2. Multiple pathways (suggesting potential additive benefits when combined with rapamycin)

Limitations & Considerations

1. Results need replication
2. Immune function impacts require investigation
   • IL-11 affects both pro- and anti-inflammatory responses
   • Lab mice live in pathogen-free environments
3. Human translation remains uncertain
4. Long-term side effects unknown

The study suggests IL-11 inhibition could be a promising longevity intervention, but significant research is needed before human applications can be considered.

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Article — Is interleukin-11 a promising new target for lifespan-extending interventions?