Scientists reveal how to potentially ‘rejuvenate’ an elderly person’s immune system

Scientists reveal how to potentially ‘rejuvenate’ an elderly person’s immune system

Scientists believe they have discovered why older people’s immune systems weaken with age, leaving them vulnerable to opportunistic pathogens that often prove fatal. The results may shed light on a path that could allow researchers to “rejuvenate” a person’s immune system – vital in the ongoing battle against COVID-19 and flu-like illnesses.

“Through this study, we have gained a new understanding of why older people are more susceptible to infectious diseases, which will allow us to identify potential new treatments,” said lead author Michael Demetriou, professor of neurology at the UCI School of Medicine, in a report.

“We have identified a potential fountain of youth for the immune system.” added Haik Mkhikian, first author of the article.

The results were published in the journal Nature Aging.

T cells are one of the most important immune cells in the body, coordinating the immune response by directly killing foreign pathogens or signaling other immune cells to kill them. As we age, our T cells become more and more impaired, weakening the immune system and leaving our body vulnerable to illnesses that usually only cause mild illnesses.

This is one of the main reasons why COVID-19 and influenza have such high mortality rates in populations aged 65 and over, and it is a key area of ​​interest for scientists trying to to extend the lifespan of humans.

One mechanism by which T cells become impaired is called N-glycan branching. Without going into extreme detail, the complex carbohydrates (called glycans) that are attached to proteins play a vital role in their functioning, and remodeling these carbohydrates can have a dramatic result.

The new findings, discovered by analyzing aging mouse and human T cells, identified that as the cells age, these “remodeled” glycans are added in increased numbers to critical immune cells, leading to impaired function that can explain why older immune systems struggle. These increases in branched glycans appeared to be due to an increase in the metabolite N-acetylglucosamine plus the activity of a cytokine called interleukin 7. The effect was particularly pronounced in women compared to men.

When old human cells were treated with proteins that inhibited branching, they found that T cells increased activation and proliferation, suggesting that N-glycan branching is likely responsible for T cell inhibition, but that it can also be reversible.

“Our research reveals that reversing the elevation of branched glycans rejuvenates human and murine T cell function and reduces the severity of Salmonella infection in aged female mice,” Demetriou said.

“This suggests several new potential therapeutic targets for revitalizing old T cells, such as branching glycan modification or age-triggered elevation of serum N-acetylglucosamine and IL-7 signaling.” Mkhikian added.

The research could allow for sex-specific targeted therapies that could boost older people’s immune systems against pathogens, although it remains to be seen whether such a treatment would be viable outside of laboratory conditions.

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