Scientists believe they have found why the immune system of older people weakens with age, leaving them susceptible to opportunistic pathogens that often prove fatal. The results may illuminate a pathway 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 adults are more susceptible to infectious diseases, which will allow us to identify potential new treatments,” said lead author Michael Demetriou, a professor of neurology in the School of ICU medicine, in a sentence
“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 eliminate 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 it’s a key area of focus for scientists trying to extend life expectancy in humans.
One mechanism by which T cells deteriorate is called N-glycan branching. Without going into extreme detail, complex carbohydrates (called glycans) that bind to proteins play an integral role in their function, and remodeling these carbohydrates can have a dramatic result.
The new results, discovered by analyzing the aging of human and mouse T cells, identified that as cells age, these “remodeled” glycans are added in greater numbers to critical immune cells, resulting in impaired function. which may explain why older immune systems struggle. These increases in branched-chain 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 to blame for T cell inhibition, but that it can also be reversible.
“Our research reveals that reversing the elevation of branched-chain glycans rejuvenates mouse and human T-cell function and reduces the severity of Salmonella infection in aged female mice,” said Demetriou.
“This suggests several potential novel therapeutic targets for revitalizing old T cells, such as disruption of branched glycans or age-induced elevation in serum N-acetylglucosamine and IL-7 signaling.” Mkhikian added.
The research could enable targeted sex-specific therapies that could boost older people’s immune systems against pathogens, though whether such a treatment would be feasible outside of laboratory conditions remains to be seen.