A recent paper demonstrating that injecting older mice with an anti-IL-11 drug extended their median lifespan made a splash in the geroscience community this summer. IL-11 is a proinflammatory cytokine that plays a role in regulating various biological processes, including hematopoiesis (the production of blood cells), bone health and remodeling, and tissue repair. Meanwhile, cytokines act as messengers between cells, helping to regulate immune responses, inflammation, and the production of blood cells. In excess or when dysregulated, cytokines can contribute to chronic inflammation and autoimmune diseases.

In this episode, Matt discusses the role IL-11 plays in the body, the ERK, AMPK, and mTOR pathways, genetic and pharmacological models of IL-11 reduction, and more. He goes over the paper's claims and evaluates whether this finding is a game-changer in the longevity field as well as what further questions he'd like to see answered in follow-up studies.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Inhibition of IL-11 signalling extends mammalian healthspan and lifespan

This is the paper Matt discusses in the podcast episode. The study's authors examined the effects of IL-11 inhibition on mouse lifespan as well as age-related disease. They demonstrate that IL-11 expression increases with age across various tissue types, and that inhibiting that expression via injection of an anti-IL-11 drug significantly increases both male and female mouse lifespan. They also present some interesting results on the effects of IL-11 on cellular senescence and white adipose tissue beiging.

Prolongation of the yeast life span by the v-Ha-RAS oncogene

As Matt notes in the podcast, this was one of the first papers—or possibly the first paper—to implicate the RAS oncogene in longevity. Published in 1990, the paper demonstrated that altering the expression of the RAS gene lead to a lifespan extension in the budding yeast Saccharomyces cerevisiae.

The Ras-Erk-ETS-Signaling Pathway Is a Drug Target for Longevity

This paper examined the role of Ras-Erk-ETS signaling in flies. The researchers found that inhibiting Ras and Erk activity led to increased lifespan, and that the FDA-approved cancer-targeting drug trametinib could facilitate this inhibition and lifespan extension.

A combination of the geroprotectors trametinib and rapamycin is more effective than either drug alone

Matt discusses this paper in a previous podcast episode. The study compared the effects of administering trametinib, the same drug discussed in the paper above this one, in combination with rapamycin to those of administering both drugs alone. It found that while both treatments had geroprotective effects in isolation, the combination treatment led to a greater lifespan extension, a reduction in liver and spleen tumors, and a lower increase in brain glucose uptake.

The impact of short-lived controls on the interpretation of lifespan experiments and progress in geroscience

This preprint, which Matt coauthored, describes the proposed "900-day rule" in greater detail. The authors describe how using short-lived controls—standards or references that help scientists understand what happens under normal conditions, so they can compare it to the results of their test—in lifespan studies can exaggerate or complicate the apparent effect of a given longevity intervention, describing this reality as "an open secret within the field of geroscience research". They make the case for longer control lifespans using various case studies.