A new study, led by researchers from the University of California, Irvine,
identifies a reason for why older adults are significantly more susceptible
to infectious diseases than younger people, a critical societal issue most
recently exemplified by the COVID-19 pandemic.
Study 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 infectious diseases, which will enable us to
identify potential new treatments," said senior author Michael Demetriou,
MD, Ph.D., 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, Ph.D., added, "We've 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 published in Nature
Aging.
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 from females more than in males due to age-associated increases
in an important sugar metabolite (N-acetylglucosamine) and signaling 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 revitalize old T cells, such as altering branched glycans or the
age-triggered elevation in serum N-acetylglucosamine and IL-7 signaling."
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. In the U.S, for
example, around 89 percent of annual deaths from influenza are in people at
least 65 years old, despite this age group representing only around 15
percent of the nation's population. 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 immunizations 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 analyzed 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.
Reference:
Haik Mkhikian et al, Age-associated impairment of T cell immunity is linked
to sex-dimorphic elevation of N-glycan branching, Nature Aging (2022).
DOI: 10.1038/s43587-022-00187-y