In this episode, Matt discusses two recent mouse lifespan studies: one focused on inhibiting IL-11 signaling, and one focused on combined trametinib and rapamycin treatment. IL-11, or Interleukin-11, is a protein that plays an important role in modulating inflammation and healing, while trametinib is an FDA-approved drug that targets certain cancers, particularly melanoma. You can find extensive discussion of rapamycin in our R-Files series linked above. Matt explains the "900-day rule" for evaluating mouse lifespan studies such as these two, and provides his take on whether these results are game-changers for the geroscience field as well as whether we should consider these interventions for human use at this time.

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 one of the papers 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.

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

This is the second paper Matt discusses in the podcast episode. The study compared the effects of administering trametinib in combination with rapamycin to those of administering both drugs alone, and 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 detail 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.

Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice

This study found that a single three-month rapamycin regimen increased life expectancy in middle-aged mice without overt detrimental side effects. The paper describes some of the positive effects rapamycin has on various mouth health measures, including cancer prevalence and the microbiome.

Functional conservation in genes and pathways linking ageing and immunity

The authors of the IL-11 paper note that IL-11 ma act on the ERK-mTORC1 and/or JAK/STAT3 pathways. This review describes seven pathways that act on immunity and lifespan, including the JAK/STAT3 and TOR pathways.