Anti-inflammation: the key to slowing down aging?

Produced by: Science Popularization China

Author: Yang Changjialian (Institute of Microbiology, Chinese Academy of Sciences)

Producer: China Science Expo

Editor's note: In order to decode the latest mysteries of life science, the China Science Popularization Frontier Science Project has launched a series of articles called "New Knowledge of Life" to interpret life phenomena and reveal biological mysteries from a unique perspective. Let us delve into the world of life and explore infinite possibilities.

In our daily lives, longevity always seems to be a topic of great interest. Everyone hopes to have a healthy and fulfilling old age. In the fifth century BC, the ancient Greek historian Herodotus first mentioned a mythical "fountain of youth" that was said to restore people's youth and grant eternal life. Although this legend is obviously full of mystery, it reflects people's dream of delaying or even reversing aging. This desire to fight aging runs through history, and modern science is gradually unveiling the veil of aging.

Chronic inflammation is a hallmark of aging

From a biological perspective, aging is associated with the accumulation of damage at the cellular and molecular levels. This damage leads to a loss of resilience in the body, which is a major risk factor for many diseases, especially neurodegenerative diseases. Age is the greatest risk factor for many brain diseases, indicating that the gradual deterioration of molecules, cells and tissues brought about by aging is at the core of biological aging.

A hallmark of aging is “chronic inflammation,” which refers to long-term, low-grade inflammation in the body in the absence of overt infection. In this chronic inflammatory state, senescent cells secrete molecules that promote inflammation or degrade the extracellular matrix, a complex network of proteins that surrounds and supports cells. While inflammation is a normal response to infection in the body, when it becomes persistent, it is associated with increased risk of morbidity and mortality from a variety of diseases.

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Inflammation in the mouse brain

(Image source: Reference 1)

IL-11 is the conductor of the aging orchestra

As we age, our bodies gradually undergo various changes, including increased inflammation. Imagine that our lives are like a grand concert, and various organs are like instruments, playing beautiful music together. In this concert, the conductor is an indispensable role, and his conduct determines the rhythm and harmony of the music. Similarly, there is an important "conductor" in our body - IL-11. This cytokine is like a naughty conductor. If its "conduct" is not accurate, it may make our body lose balance.

Research suggests that regulating IL-11 may help slow the aging process and help keep us healthy.

IL-11 (Interleukin-11) is a pro-inflammatory cytokine that plays an important role in the human body. Under normal circumstances, IL-11 is involved in regulating immune responses, but when its levels are too high, it can cause unnecessary inflammation. As we age, the level of IL-11 gradually increases in the body, and this increase seems to be closely related to aging-related health problems. Just like a conductor who makes frequent mistakes during his performance, causing the orchestra's performance to become chaotic, the overactivity of IL-11 can also disrupt the balance in the body and cause a series of health problems.

Adjusted the relationship between "Command" effect and longevity

Levels of IL-11 rise dramatically in mice as they age. This increase has been linked to several age-related diseases, including metabolic problems, muscle loss and liver problems.

Using gene editing technology, we can delete the IL-11 gene or IL-11 receptor gene in mice and create different mouse models. Those mice whose IL-11 was inhibited or injected with anti-IL-11 antibodies showed healthier old age, including better metabolic health, less fat accumulation, slower muscle loss, and reduced liver fat synthesis. These mice not only improved their physical condition, but also extended their lifespan.

These findings suggest that IL-11 may contribute to a variety of health problems during aging. Since the main cause of death in laboratory mice is cancer, this result also provides a new perspective for studying human aging.

Effects of pro-inflammatory protein inhibition on lifespan

(Image source: Reference 2)

The secrets hidden in the "conductor"

After we discovered IL-11, this low-key "conductor", people began to want to know more about it. On the one hand, we want to know the specific process by which the increase of IL-11 promotes age-related diseases such as cancer, metabolic disorders, and muscle loss. For example, is the progression rate of these diseases changed in mice in which IL-11 is inhibited? Is the increase in IL-11 local or systemic? Answers to these questions will help us better understand the mechanisms of aging and provide new ideas for future treatments.

On the other hand, we are still exploring the reasons why IL-11 levels increase, and hope to treat or prevent age-related diseases by regulating IL-11. For example, does the increase in IL-11 levels vary from tissue to tissue? Can this increase be improved by drugs or other treatments? The answers to these questions may have a profound impact on future medical research and treatment.

Conclusion

The discovery of IL-11 provides us with a new perspective to help us understand the aging process. By regulating this "conductor of the orchestra", we hope to make the "music" of aging more harmonious. In the future, scientists will continue to explore IL-11 and its related mechanisms to provide us with more hope and solutions to achieve the goal of healthy longevity.

References:

1.Eggen BJL. How the cGAS-STING system links inflammation and cognitive decline. Nature. 2023;620(7973):280-282.

2.Miller RA. Blocking an inflammatory protein slows the pace of ageing. Nature. 2024;632(8023):35-36.