Photo caption: Zongqi Xia, associate professor of neurology and of biomedical informatics, School of Medicine, and of clinical and translational science at the University of Pittsburgh. Photography courtesy of Xia.
By Phoebe Ingraham Renda
As people age, their immune systems naturally become less reactive. In the case of people with multiple sclerosis (MS), this can mean fewer disease flare-ups. As a result, clinical trials have been testing whether older adults with MS still benefit from immune-modulating drugs, as these medications increase the risk of infections.
“Current MS treatments try to attack the root cause of this autoimmune disease by modulating some aspects of immune activity,” says Zongqi Xia, associate professor of neurology and of biomedical informatics, School of Medicine, and of clinical and translational science at the University of Pittsburgh. “But as people age, the underlying disease process becomes less active, and the benefit from taking these medications is reduced.”
A recent study by Xia and colleagues at Cornell, published on June 5, 2025, in the Journal of Neuroinflammation, sheds light on a biological mechanism that causes MS disease activity to decline with age.
Older, Calmer
MS is a disease where the immune system mistakenly attacks the protective coating around nerves in the brain and spinal cord. This coating contains myelin basic protein (MBP) as a key component. In such attacks, an immune cell called Th17 plays a big role—Th17 cells produce inflammatory signals that target MBP.
Over time, inflammation and the resulting damage disrupt neuronal communication between the brain, spinal cord and the body. Those disruptions lead to symptoms like vision problems, fatigue and difficulty with walking or balance. These Th17 responses are elevated when patients experience an acute relapse, or flare-up, of their symptoms.
“As people age, their biology changes—so, the way they respond to immunomodulating treatments changes over time,” says Xia. “We know from clinical observations and clinical trials of discontinuing treatment in older individuals that there is a potential rationale for removing these treatments for certain patients as they get older, but what is the biological mechanism?”
Using blood samples from people with MS across different ages, Xia and collaborator Mandy McGeachy, professor of microbiology and immunology at Cornell, explored whether Th17 cells’ aggression toward MBP changed with age. The team isolated immune cells from each patient’s blood sample and exposed them to MBP in a dish to see how fiercely they attacked the protein. They found that Th17 immune cells from older patients were less aggressive and produced fewer inflammatory signals in response to MBP, correlating with lower MS disease activity.
Sex-Biased Shifts
In the study, the team observed that the aging-related decline in Th17 activity occurs more sharply in women than men, suggesting a sex difference in the immune-aging effect. This finding helps explain why women, who generally exhibit a stronger immune response, tend to experience more active inflammation and MS disease activity early in life. The observation also aligns with clinical data showing that MS affects more women than men at a ratio of 3:1.
Better Understanding, Better Trials
“We’ve described a potential mechanism that would explain why people, as they get older, will not benefit as much from immune treatments that target a key component of the immune system,” says Xia.
To improve MS treatment and design better clinical trials—especially those testing whether older patients still benefit from immunomodulating therapies—we need to gain a deeper understanding of the disease’s underlying biology and why it progresses differently in women and men, says Xia.