Lecture Notes: Interleukin 11 (IL-11) and Aging

Introduction to Interleukin 11 (IL-11)

• IL-11 Overview
  • A gene in the human body responsible for creating a protein.
  • Activates fibroblasts and immune cells.
  • Inherited from evolutionary ancestors (fish).
  • Causes inflammation, fibrosis, and impedes tissue regeneration in humans.

Discovery and Initial Characterization

• Historical Context
  • Mischaracterized before 2016-2017.
  • Identified as profibrotic and pro-inflammatory in heart and kidney tissues.
  • Expanded to show effects in multiple tissues.

Research into Aging

• Transition to Aging Research

  • Initial studies focused on fibrosis and tissue scarring.
  • Accidental discovery: High IL-11 levels in older animals.
  • Found to increase in all tissues of aging mice.

• Impact on Aging

  • IL-11 linked to multimorbidity, diseases of aging.
  • Affects various body functions: eyesight, hearing, hair, muscles, heart, kidneys.
  • Raising questions about its role in aging.

Gene Manipulation and Therapeutic Approaches

• Gene Manipulation in Mice

  • Genome manipulation to turn off IL-11 gene showed improved aging diseases.

• Antibody Therapy

  • Antibodies bind and neutralize IL-11.
  • Successful trials with 55-year-old equivalent mice.
  • Improved muscle strength, lung function, skin, hearing, and vision.
  • Demonstrated potential for human therapeutic interventions.

Future Directions and Implications

• Sence Research Interest

  • Focus on how IL-11 relates to cancer, aging, and related diseases.
  • Exploring interrelated mechanisms for better treatment design.

• Therapeutic Potential

  • Single reagent (anti-IL-11 therapy) improving healthspan and lifespan.
  • Global target population for therapy.
  • Challenges: Human trial funding and regulatory issues.
  • Promising safety profile from genetic and animal study data.

Conclusion

• IL-11 is an evolutionarily inherited gene causing aging-related diseases.
• Gene manipulation and antibody therapies show potential in combating aging diseases.
• Future work needed to translate findings to human treatments.