Taurine helps regulate inflammation linked to aging, Yale study finds

Sustained low-level inflammation is a hallmark of the aging process. The accumulating damage persistently activates the innate immune system-the body’s first line of defense-leading to what is known as inflammaging, functional decline and chronic diseases of old age.

Unlike the adaptive immune system, which switches on and off based on the specific pathogens it recognizes, innate immune sentinels such as macrophages can recognize a diverse array of danger signals. The mechanism of this pattern recognition has remained an enigma, however.

In a new study published Oct. 23 in Cell, researchers at Yale School of Medicine found that the amino acid taurine is key to the way the innate immune system senses danger signals. Even more, boosting taurine levels may diminish the effects of inflammaging.

Biology has lots of surprises. And the biggest surprise in this study is that taurine is controlling the innate sensing mechanism.”

Vishwa Deep Dixit, PhD, senior author, Waldemar Von Zedtwitz Professor of Pathology and director, Yale Center for Research on Aging (Y-Age), Yale School of Medicine

Dixit first became interested in taurine after finding that it increased as people restricted their calorie intake for up to one year as part of the CALERIE study. He and his team also found that moderate calorie restriction led to lower chronic inflammation-something that enhances healthy lifespan. But calorie restriction is not practical for most adults and there was little evidence as to whether taurine linked metabolism to the immune system.

“We wanted to test whether taurine is just a passenger or a driver of the reduction in inflammatory response caused by caloric restriction,” Dixit says.

Taurine is a checkpoint of inflammation

Dixit expected that taurine levels might decrease with age. After all, aging is associated with an increase in inflammation. But that did not turn out to be true.

By comparing the blood serum of young (20- to 40-year-old) and older (60- to 99-year-old) people, his team found that taurine actually increased with age. The finding was surprising and suggested that taurine does not drive aging, says Chenyang Guan, PhD, the first author of the study and a postdoctoral associate in the Dixit lab.

The researchers then suspected that the increase in taurine with age may be a failed attempt to reduce inflammation.

Inflammaging is caused in part by the activation of a molecular complex called the NLRP3 inflammasome. When macrophages-the front line of innate immune defense-encounter danger signals, the NLRP3 inflammasome components assemble within macrophages, causing inflammation. Lowering overly active NLRP3 can enhance lifespan in mice and protect against inflammaging-driven functional decline, research has shown.

To find out if taurine plays a role in the NLRP3-mediated inflammation pathway, Guan challenged macrophages in a culture dish with various danger signals, including bacterial toxins. As the signals appeared, NLRP3 complexes began to assemble within the macrophages. Surprisingly, as the complexes were forming, macrophages released up to 80% of their taurine.

Guan then wondered whether the release of taurine itself allows macrophages to sense all sorts of very different danger signals to initiate NLRP3 assembly. Sure enough, it did; restoring lost taurine back in cells stopped the downstream inflammatory responses initiated by the formation of NLRP3 inflammasome.

The results of the study suggest that the innate immune system senses perturbation in cells’ internal environments through the loss of taurine, leading to activation of the NLRP3-mediated inflammation.

“Since the innate immune system does not have specific receptors for each and every different type of danger signal, this pattern recognition has always been a mystery,” Dixit says. “Now we know that taurine allows immune sensing and is one of the brakes within the cells that is keeping the inflammasome in check.”

If the release of taurine initiates NLRP3 inflammation, would supplementing the macrophages with taurine stop inflammation? The researchers wondered.

To answer that question, they supplied macrophages with fresh taurine and found that it inhibited the activation of the NLRP3 inflammasome. On the other hand, when they lowered taurine in macrophages, it accelerated NLRP3-driven inflammation even in young mice.

“What we have answered is the first step of the puzzle in what causes this very critical innate immune system sensor to be activated,” Dixit says.

His team is now investigating what happens to the taurine after it exits the macrophages and whether these findings could translate to something that can benefit older adults.