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Aging & Longevity

Anti-Aging Antibody Significantly Extends Life by 22% in Breakthrough Study

A potentially transformative antibody that inhibits the IL-11 protein increases mouse lifespan by 22% by targeting the same pathways as metformin and rapamycin.

AI-generated depiction of an antibody.
By Griffin Dean

Key Points: 

  • Inhibiting the signaling molecule IL-11 prolongs the lifespan of male and female mice by 22.3%. 
  • IL-11 inhibition also reduces cancer incidence and improves body composition and strength. 
  • Blocking IL-11 has similar effects to metformin and rapamycin. 

Scientists from Duke–National University of Singapore Medical School have significantly increased the lifespan of mice by injecting them with an antibody that inhibits a protein called interleukin-11 (IL-11).  

A survival curve graph from the original study.
(Widjaja et al., 2024 | Nature) Blocking IL-11 Prolongs Mouse Lifespan. Male and female mice injected with an antibody that blocks IL-11 (Anti-IL-11, blue) starting from 75 weeks of age (red dotted line) lived 22.3% longer than mice injected with a control antibody (IgG, black). More specifically, the median lifespan (Cumulative survival probability of 0.5) was 120.9 weeks for control mice and 155.6 weeks for the mice treated with the IL-11-inhibiting antibody, called X203.

In the mice that lived longer, autopsies revealed a lower incidence of tumors, suggesting that inhibiting IL-11 may delay or prevent cancer development. Furthermore, inhibiting IL-11 was shown to reduce fat mass, increase lean mass, boost full-body strength, and prevent frailty, a measure of overall health. Together, these findings demonstrate that inhibiting IL-11 can prolong lifespan and improve healthspan — the duration of life lived in good health. 

Inhibiting IL-11 Blocks Multiple Key Drivers of Aging 

Until recently, IL-11 was largely misunderstood by scientists. The protein was once thought to have anti-inflammatory, anti-scarring, and pro-regenerative properties. However, scientists now believe it possesses opposite properties and is pro-inflammatory, pro-scarring, and anti-regenerative. 

Still, IL-11 is a powerful signaling molecule that modulates the master nutrient sensors AMPK and mTOR. AMPK is activated during nutrient deprivation, such as when we are in a fasted state. When activated, AMPK triggers cell survival programs that protect against cellular aging, including the inhibition of mTOR. For this reason, the anti-diabetes drug metformin, which activates AMPK, was popularized as one of the first repurposed anti-aging drugs. 

An even more promising repurposed anti-aging candidate is the immune-modulating drug rapamycin. Rapamycin inhibits mTOR (mammalian target of rapamycin) and has repeatedly been shown to robustly increase the lifespan of mice. Importantly, the Duke researchers found that inhibiting IL-11 activates AMPK (similar to metformin) and inhibits mTOR (similar to rapamycin). 

Furthermore, the researchers showed that IL-11 inhibition largely prevents the age-related increase in senescent cells. Senescent cells are thought to exacerbate chronic low-grade inflammation, referred to as inflammaging because it underlies many chronic age-related diseases. Thus, inhibiting IL-11 alleviates multiple key drivers of aging, including deregulated nutrient sensing, cellular senescence, and chronic inflammation. 

An IL-11 Antibody for Humans 

Previously, higher levels of IL-11 were observed in older individuals, suggesting the protein increases with age in our bodies. To help confirm this, Duke researchers demonstrated that IL-11 increases with age in the liver, muscle, and visceral fat of mice. However, whether inhibiting IL-11 in older adults is safe remains an open question. 

Scientists like Charles Brenner, Ph.D., have pointed out that IL-11 is an important component of the immune system. Laboratory mice are kept in a pathogen-free environment, largely protecting them from infections. If blocking IL-11 in humans suppresses the immune system, which is already weakened in older individuals, it could lead to a higher incidence of infection and illness. Therefore, studies will be needed to determine how inhibiting IL-11 in humans affects the immune system. 

As it turns out, we may soon know if inhibiting IL-11 is safe for humans. The German-based pharmaceutical company Boehringer Ingelheim has begun a Phase I clinical trial to test the safety and tolerability of an IL-11 inhibitor antibody in healthy volunteers. If successful, the IL-11 inhibitor will go on to be tested for treating fibrosis — scarring of the organs and tissues. Fibrotic diseases, which can trigger organ failure and cancer, accounted for 35% of global deaths in 2019. This means that if inhibiting IL-11 prevents fibrosis, many individuals worldwide could live longer. 

The Duke researchers conclude, 

“Our data suggest that anti-IL-11 therapy, which has a reassuring safety profile and is currently in early-stage clinical trials for fibroinflammatory diseases, is a potentially translatable approach for extending human healthspan and lifespan.”

Source

Widjaja, A. A., Lim, W., Viswanathan, S., Chothani, S., Corden, B., Dasan, C. M., Goh, J. W., Lim, R., Singh, B. K., Tan, J., Pua, C. J., Lim, S. Y., Adami, E., Schafer, S., George, B. L., Sweeney, M., Xie, C., Tripathi, M., Sims, N. A., . . . Cook, S. A. (2024). Inhibition of IL-11 signalling extends mammalian healthspan and lifespan. Nature, 1-9. https://doi.org/10.1038/s41586-024-07701-9

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