Scientists believe they have found why elderly people’s immune systems weaken with age, leaving them susceptible to opportunistic pathogens that often prove fatal. The results may illuminate an avenue that could allow researchers to "rejuvenate" a person’s immune system – vital in the ongoing battle against COVID-19 and flu-like diseases.
“Through this study, we have gained a new understanding of why older adults are more susceptible to infectious diseases, which will enable us to identify potential new treatments,” said senior author Michael Demetriou, a professor of neurology at the UCI School of Medicine, in a statement.
“We’ve identified a potential fountain of youth for the immune system.” added Haik Mkhikian, first author of the paper.
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 either 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 diseases that usually just cause mild sickness.
This is one of the largest reasons why COVID-19 and the flu have such high mortality rates in populations aged 65+, and is a key area of focus for scientists attempting to prolong lifespans in humans.
One mechanism by which T-cells become impaired is called N-glycan branching. Without getting into the extreme details of it, complex carbohydrates (called glycans) that are attached to proteins play an integral role in how they function, and remodeling of these carbohydrates can have a dramatic outcome.
The new results, discovered by analyzing aging mouse and human T-cells, identified that as cells age, these "remodeled" glycans are added in increased numbers to the critical immune cells, resulting in impaired function that may explain why older immune systems struggle. Such 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 females when compared to males.
When old human cells were treated with proteins that inhibited branching, they discovered the T-cells increased activation and proliferation, suggesting both N-glycan branching is likely at fault for the inhibition of T-cells, but that it also may be reversible.
“Our research reveals that reversing the elevation in branched glycans rejuvenates human and mouse T cell function and reduces severity of Salmonella infection in old female mice,” said Demetriou.
“This suggests several potential novel therapeutic targets to revitalize old T cells, such as altering branched glycans or the age-triggered elevation in serum N-acetylglucosamine and IL-7 signaling.” Mkhikian added.
The research could allow for sex-specific targeted therapies that could bolster elderly people’s immune systems in the face of pathogens, though it remains to be seen if such a treatment would be viable outside laboratory conditions.