Science, Medicine, and the Anesthesiologist

Anesthesiology December 2024, Vol. 141, A13–A15.

The cell signaling pathways ERK, AMPK, and mTORC1 are well-known lifespan regulators in different species. In aging animals, these pathways play a crucial role in terms of activating hallmarks of aging such as, for example, mitochondrial dysfunction or cellular senescence. Conversely, interference with these pathways such as inhibition of mTOR is known to increase lifespan in rodents. An important aspect of aging is immunosenescence with increased activation of interleukin (IL)-6 and therefore increased inflammation, known as a hallmark of aging. This study tested the hypothesis of whether IL-11, a proinflammatory and also profibrotic cytokine of the IL-6 family, promotes age-associated pathologies and reduces lifespan in mice. In aging mice, IL-11 was upregulated in various tissues (liver, visceral gonadal white adipose tissue, and skeletal muscle), propagating thereby aging pathologies through the ERK-AMPK-mTORC1 axis interaction. Deletion of IL-11 or its receptor IL-11ra1 provided protection against metabolic decline, frailty, and multi-morbidity in aging animals, thereby increasing lifespan; genetic deletion of IL-11 led to an extension of life by 25% on average in both sexes. In anti-IL-11, blocking studies in 75-week-old mice metabolism and muscle function were improved, with a reduction of frailty and an overall extension of the median lifespan of 22.5% and 25% in male and female animals, respectively.

Take home message: This murine study shows promising results of blocking the proinflammatory cytokine IL-11 in older mice, positively affecting age-related decline and increasing lifespan in both male and female animals. The role of an anti-IL-11 therapy currently being tested in clinical trials for the treatment of fibrotic lung disease on aging in humans is not yet known.