Academy

Interleukin-11 in Aging and Longevity

Overview: Interleukin-11 (IL-11) is a signaling protein implicated in inflammation, fibrosis, and tissue repair. While essential for normal physiological processes, dysregulated IL-11 activity contributes to age-associated pathologies like pulmonary fibrosis, liver cirrhosis, and cardiovascular stiffening.

Biological Role:

• Produced by stromal and epithelial cells in response to injury or stress.
• Activates IL-11 receptor alpha (IL-11Rα) and gp130, triggering JAK/STAT and MAPK pathways.
• Promotes fibroblast proliferation and collagen synthesis for wound healing.

IL-11 and Fibrosis:

• Chronic IL-11 signaling leads to excessive extracellular matrix (ECM) deposition.
• Fibrotic scarring impairs organ elasticity and function, accelerating age-related decline.
• Inhibiting IL-11 can reverse or halt fibrosis in preclinical models.

Therapeutic Targeting: Monoclonal antibodies against IL-11—such as 9MW3811—bind the cytokine directly, preventing receptor engagement and downstream signaling. This targeted approach reduces systemic immunosuppression compared to broad anti-inflammatory drugs.

Preclinical Evidence:

1. Mice treated with anti-IL-11 antibodies show reduced lung collagen content and improved respiratory function.
2. Blocking IL-11 signaling extends lifespan by preserving muscle function, telomere integrity, and reducing tumor incidence.
3. Safety profiles in animal studies demonstrate tolerability with minimal off-target effects.

Clinical Development:

• Phase I trials have assessed safety and pharmacokinetics in healthy volunteers and fibrotic disease patients.
• Next steps include dose-escalation studies and efficacy trials in idiopathic pulmonary fibrosis (IPF) and other fibrotic conditions.

Implications for Longevity Science:

• Targeting IL-11 offers a precision medicine strategy to mitigate chronic inflammation and fibrosis—key drivers of aging.
• Combining anti-IL-11 therapies with lifestyle interventions and regenerative approaches could enhance healthspan.
• Ongoing research explores IL-11’s role in vascular aging, neuroinflammation, and metabolic disorders.

Understanding IL-11’s dual roles in repair and pathology is vital for developing safe, effective longevity therapeutics aimed at extending healthy human lifespan.