Novel method to reduce risk of infectious disease in the elderly

Infectious Disease

A research team from the University of California has developed a method to reduce the risk of the elderly developing an infectious disease.

Why are the elderly more likely to develop an infectious disease?

University of California researchers have identified why older adults are significantly more susceptible to contracting an infectious disease compared to younger people, a critical societal issue that has most recently been highlighted by the COVID-19 pandemic. The researchers’ results also pave the way for new potential therapeutic targets to rejuvenate the immune system in older adults and thereby reduce their risk of infectious disease.

“Through this study, we have gained a new understanding of why older adults are more susceptible to developing an infectious disease, which will enable us to identify potential new treatments,” explained Michael Demetriou, Senior Author, MD, PhD, a Professor of Neurology at the UCI School of Medicine and Chief of the Division of Multiple Sclerosis and Neuroimmunology at UCI.

First Author and Assistant Professor in the UCI Department of Pathology, Haik Mkhikian, MD, PhD, added: “We have identified a potential fountain of youth for the immune system.”

The study, titled, ‘Age-associated impairment of T cell immunity is linked to sex-dimorphic elevation of N-glycan branching,’ was recently published in the journal Nature Ageing.

How did researchers identify this ‘potential fountain of youth’?

It has been scientifically observed that T cell immunity declines with ageing, which increases both severity and mortality from contracting an infectious disease. T cells are essentially 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.

Scientists demonstrated that the branched glycans increased with age in T cells from females more so 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,” said Demetriou.

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.”

Ageing-associated immune dysfunction: How does this contribute to morality?

Ageing-associated immune dysfunction – often referred to as immunosenescence – contributes to increased morbidity and mortality from both neoplastic and infectious diseases in adults aged 65 years and older.

In the US, approximately 89% of annual deaths from the infectious disease influenza are contracted by people who are at least 65 years old. This is despite the age group only representing approximately 15% of the nation’s population.

Additionally, the vulnerability of older adults contracting an infectious disease has been emphasised by the recent emergence of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Increased morbidity and mortality in older adults also occur with common bacterial infections, such as those caused by the enteric pathogen Salmonella.

The efficacy of immunisations declines with age, which increases the risk of contracting an infectious disease in older adults. Thus, the rapidly ageing population in the developed world exacerbates this issue and intensifies the requirement for interventions that effectively target immunosenescence.

This research has revolutionised this topic because previous studies have examined transcriptome changes in highly purified aged T cell subsets, while in this study, scientists 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 funded by the National Institute of Allergy and Infectious Disease, the National Centre for Complementary and Integrative Health, The Burroughs Wellcome Fund, and a predoctoral fellowship from the American Heart Association.


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