Study explores immune system rejuvenation in the elderly

An international study has identified why older adults are more susceptible to infectious diseases compared to younger people, paving the way for new potential therapeutic targets to rejuvenate the immune system in older adults.

The study by researchers from the University of California, Irvine, has identified “a potential fountain of youth for the immune system”, claimed Haik Mkhikian, MD, PhD, first author and assistant professor at the University of California, Irvine (UCI), Department of Pathology.

“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 and study-lead Michael Demetriou, MD, PhD, a professor of neurology at the UCI School of Medicine and chief of the Division of Multiple Sclerosis and Neuroimmunology at UCI.

T cell immunity declines with aging, thereby increasing severity and mortality from infectious disease. T cells are the quarterback of the immune system and coordinate immune responses to fight off infections. The addition of complex and branched carbohydrate chains (‘glycans’) to proteins suppresses T cells’ function.

In this study, researchers show that the branched glycans increase with age in T cells in females more than in males due to age-associated increases in an important sugar metabolite (N-acetylglucosamine) and signalling by the T cell cytokine interleukin-7.

“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,” Demetriou said.

Mkhikian added, “This suggests several potential novel therapeutic targets to revitalise old T cells, such as altering branched glycans or the age-triggered elevation in serum N-acetylglucosamine and IL-7 signalling.”

Aging-associated immune dysfunction, referred to as immunosenescence, contributes to increased morbidity and mortality from both infectious and neoplastic diseases in adults aged 65 years and older. More recently, the vulnerability of older adults to viral infections has been tragically highlighted by the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Increased morbidity and mortality in older adults also occurs with common bacterial infections such as those caused by the enteric pathogen Salmonella. Furthermore, efficacy of immunisations declines with age, further increasing risk of infection in older adults. The rapidly aging population in the developed world exacerbates this issue and heightens the need for interventions that effectively target immunosenescence.

Previous studies examined transcriptome changes in highly purified aged T cell subsets. In this study, researchers analysed T cell populations by age and sex, with results suggesting sex-specific differences that imply that effective interventions to reverse immune dysfunction in older adults may require sex-specific strategies.

The study was supported by funding from the National Institute of Allergy and Infectious Diseases, the National Center for Complementary and Integrative Health, The Burroughs Wellcome Fund and a pre-doctoral fellowship from the American Heart Association.

Image caption: Findings from the study, led by Michael Demetriou, MD, PhD, may pave the way for new potential therapeutic targets to rejuvenate the immune system in older adults and thereby reduce their risk of infectious disease. UCI/Steve Zylius.