Scientists believe they have discovered why the immune systems of older people weaken with age, leaving them susceptible to opportunistic pathogens that are often fatal. The results could illuminate 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 gained a new understanding of why older adults are more susceptible to infectious diseases, which will allow us to identify potential new treatments,” said senior author Michael Demetriou, professor of neurology at the UCI School of Medicine. in a statement.
“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 increasingly impaired, weakening the immune system and leaving our bodies vulnerable to illnesses that usually only cause mild illness.
This is one of the biggest reasons why COVID-19 and the flu have such high death rates in populations over 65 and is a key area of focus for scientists trying to extend lifespan in humans.
One mechanism by which T cells are harmed is called N-glycan branching. Without going into the extreme details of this, the complex carbohydrates (called glycans) that are attached to proteins play a key role in how they function, and the remodeling of these carbohydrates can have a dramatic result.
The new results, discovered by analyzing human T cells and aged mice, identified that as cells age, these “remodeled” glycans are added in greater numbers to critical immune cells, resulting in impaired function that may explain why older immune systems struggle. These increases in branched glycans appear to be due to an increase in the N-acetylglucosamine metabolite 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 inhibit branching, they found that T cells increased activation and proliferation, suggesting that N-glycan branching is likely to blame for T cell inhibition, but that it may also be reversible. .
“Our research reveals that reversing the elevation in branched glycans rejuvenates mouse and human T cell function and reduces the severity of Salmonella infection in old female mice,” said Demetriou.
“This suggests several potential new therapeutic targets for revitalizing old T cells, such as altering branched glycans or the age-triggered elevation in serum N-acetylglucosamine and IL-7 signaling.” added Mkhikian.
The research may allow for targeted sex-specific therapies that can bolster the immune system of older adults in the face of pathogens, although it remains to be seen whether such a treatment would be viable outside of laboratory conditions.