Older people are more vulnerable to infectious diseases and that these cause severe symptoms, something that has been verified with the COVID-19 pandemic, and that is also observed every year during the flu season. Now, a new study led by researchers at the University of California Irvine (UCI) (USA) has revealed the reason why this happens and could help find new therapeutic targets to rejuvenate the immune system of older adults and, in this way, reduce the risk of them suffering from infections.
“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 Dr. Michael Demetriou, professor of neurology in the College. of Medicine at the UCI and head of the Division of Multiple Sclerosis and Neuroimmunology at the UCI and lead author of the study, which has been published in Nature Aging. “We have identified a potential fountain of youth for the immune system,” added Dr. Haik Mkhikian, first author and assistant professor in the UCI Department of Pathology.
Revitalize aging T cells to boost immunity
Immune dysfunction associated with aging is known as immunosenescence and contributes to increased morbidity and mortality from infectious and neoplastic diseases in individuals aged 65 years and older. This increased morbidity and mortality in older people also occurs when they contract common bacterial infections, such as those caused by the enteric pathogen Salmonella. In addition, the effectiveness of vaccines also decreases as we age, which further increases the risk of infection in the elderly, hence the importance of carrying out interventions aimed at combating immunosenescence effectively.
“Reversing the elevation of branched glycans rejuvenates T-cell function and reduces the severity of Salmonella infection”
The aging process decreases the immunity of T cells and this increases the severity of infectious diseases and the chances of dying from them. T cells are the ‘field marshal’ of the immune system and are responsible for coordinating immune responses to fight infections. The addition of complex, branched carbohydrate chains (‘glycans’) to proteins suppresses T-cell function.
The researchers analyzed T-cell populations by age and gender, and the results suggest that there are gender-specific differences, implying that effective interventions to reverse immune dysfunction in older adults may require gender-specific strategies. Specifically, they have shown that branched-chain glycans increase with age in female T cells more than in males as a result of age-associated increases in an important sugar metabolite (N-acetylglucosamine) and cell signaling. T-cell cytokine interleukin-7.
“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,” explained Demetriou. Mkhikian adds, “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.”
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