Summary: A new study has identified a novel biological mechanism driving cognitive decline and accelerated aging in individuals living with chronic viral infections. The research reveals that the degradation of protective, anti-inflammatory sugar molecules, known as glycans, fuels chronic systemic inflammation in patients with HIV.
By deploying sialidase inhibitors (a class of drugs primarily used to treat influenza, including Tamiflu), investigators successfully preserved these glycan structures in preclinical models, reducing neuro-inflammation, slowing biological aging, and protecting memory circuits.
Key Facts
- The Persistent Cognitive Deficit: At least 25% of individuals living with HIV experience memory and cognitive impairment despite undergoing effective, viral-suppressing antiretroviral therapy.
- Glycan Degradation Fueling Aging: The study isolates a new pathological culprit: the breakdown of protective blood-protein sugars called glycans. When these molecules degrade, inflammation becomes chronic, driving the immune system into an overactive state that accelerates biological aging.
- Human Cohort Evaluation: Researchers discovered the sugar-loss mechanism by analyzing blood profiles from a cohort of more than 100 HIV-positive participants enrolled in the AIDS Clinical Trials Group, cleanly linking glycan degradation to clinically verified cognitive decline.
- Repurposing Anti-Flu Mechanics: Sialidase inhibitors like Tamiflu (oseltamivir) typically combat influenza by blocking a viral enzyme. In this study, scientists used the drugs to inhibit endogenous host enzymes that would otherwise break down the body’s protective, anti-inflammatory glycans.
- Preclinical Memory Rescue: Administered to cellular and mouse models of HIV, the sialidase inhibitor regimen successfully shielded glycan structures, lowered inflammation markers, reversed signs of premature aging, and preserved cognitive performance.
- The Menopausal Acceleration Axis: The loss of protective glycans is highly distinct across biological sexes. While glycan degradation progresses at a steady, linear rate in aging men, women retain a more robust anti-inflammatory glycan profile until a rapid, aggressive shift toward pro-inflammatory states occurs around menopause.
- Translational Pipeline Objectives: Lead investigator Dr. Mohamed Abdel-Mohsen notes that while these flu drugs are safely approved for short-term virus suppression, further preclinical optimization is mandatory to determine the appropriate dosing, duration, and biomarker predictive capabilities required for long-term human neuroprotection.
Source: Northwestern University
A class of flu drugs may reduce cognitive decline and premature aging in people living with chronic viral infection, reports a new study led by Northwestern University that began with blood samples from people with HIV and extended into preclinical drug trials.
The findings point to a potential new therapy for cognitive problems in people with HIV, with broader implications for other aging-related diseases, such as dementia.
The study will be published June 5 in Med, a journal from Cell Press.
At least a quarter of people living with HIV develop problems with memory and thinking, even with effective antiretroviral treatment. Reasons for these cognitive symptoms have remained unclear. In this study, the Northwestern scientists identified a new biological culprit: the degradation of protective sugar molecules in our bodies, known as glycans, that normally help keep inflammation in check. When inflammation becomes chronic, it can accelerate biological aging by driving the immune system to overreact for too long.
The scientists identified the new sugar mechanism by analyzing blood samples from more than 100 individuals with HIV, both with and without cognitive impairment. Then, the research team conducted lab and mouse studies, where they found that flu drugs (a combination of Tamiflu and another experimental drug) preserved the sugar molecules and protected the brain.
“We are not saying yet that people should take flu drugs to prevent cognitive decline,” explained study lead author Mohamed Abdel-Mohsen, associate professor of medicine in the division of infectious diseases at Northwestern University Feinberg School of Medicine. “We are saying that our findings open the door to testing whether this drug class, or better next-generation versions, could be repurposed for brain and aging-related complications,” he added.
A Northwestern Medicine patient who has lived with HIV for nearly 40 years is available for interviews about the importance of HIV research.
How the study was conducted
First, the scientists analyzed blood samples from people with HIV enrolled in the AIDS Clinical Trials Group. All participants were on HIV treatment and were characterized as having either normal cognition or cognitive impairment based on clinical testing. Abdel-Mohsen’s team analyzed sugar patterns on the people’s blood proteins and found that there was a clear link between degradation of the sugar molecules and cognitive decline.
Then, the team used immune cells from people living with HIV and mouse models with HIV to test whether the sugar degradation increased inflammation. Finally, the Northwestern scientists used the flu drugs to show that, in mice, preserving the sugar molecules reduced inflammation, slowed biological aging and protected memory.
The flu drugs are called sialidase inhibitors and include Tamiflu, also known as oseltamivir. These drugs typically treat the flu by blocking a viral enzyme that helps the virus spread. In this study, the scientists used them differently by blocking other enzymes in the body that degrade the protective sugar molecules.
Stronger effects in women
The sugar degradation was more pronounced in women in the study. Abdel-Mohsen says in men, these sugar changes tend to occur gradually and steadily with aging. But in women, the degradation starts slower and then accelerates around menopause.
“Before menopause, women show a slower loss of anti-inflammatory glycans and slower accumulation of pro-inflammatory glycans compared with men, but around menopause there is a rapid shift toward a more inflammatory glycan profile,” said Abdel-Mohsen, who also is a member of Feinberg’s Potocsnak Longevity Institute.
Next steps
Abdel-Mohsen said his team is now working on two fronts: optimizing potential treatment strategies with the flu drugs and determining whether the sugar molecules can predict future cognitive decline via new blood biomarker tests.
“On the treatment side, we want to do more preclinical work to optimize the approach. Although some sialidase inhibitors are already used safely in people for influenza, they have not been tested for this purpose, dose or duration,” he said.
Key Questions Answered:
A: By changing how it targets enzymes in the body. While Tamiflu normally blocks a viral enzyme to stop the flu from spreading, Northwestern researchers used it to block a completely different set of human enzymes that destroy glycans, the protective sugar molecules that keep dangerous, brain-aging inflammation under control.
A: Because it triggers a rapid shift in the body’s sugar defenses. Before menopause, women naturally maintain a highly resilient shield of anti-inflammatory glycans. However, around menopause, this protective sugar coating degrades rapidly, accelerating the accumulation of pro-inflammatory signals far faster than the steady, gradual decline seen in aging men.
A: No, clinical adoption is not ready yet. Lead author Dr. Mohamed Abdel-Mohsen stresses that while standard sialidase inhibitors are safe for short-term flu treatment, they have never been tested in humans for this specific cognitive purpose, dosage, or long-term duration. The team is currently optimizing these treatment lines in preclinical models first.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuropharmacology and cognitive decline research news
Author: Ben Schamisso
Source: Northwestern University
Contact: Ben Schamisso – Northwestern University
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Inhibiting glycan degradation prevents HIV-induced inflammaging and cognitive impairment” by Leila B. Giron, Alejandra Borjabad, Eran Hadas, Janeway Granche, Erika G. Marques de Menezes, Thomas A. Premeaux, Hongxia He, Stephen T. Yeung, Shalini Singh, Courtney Friday, Joshua Glover, Eric Balboa, Derrick Dopkin, Michelle Burrows, Anthony Secreto, Nicolas Skuli, Hiroaki Tateno, Paul W. Denton, Frank Palella, Michael J. Corley, Lishomwa C. Ndhlovu, Philip J. Norris, Katherine Tassiopoulos, David J. Volsky, and Mohamed Abdel-Mohsen. Med
DOI:10.1016/j.medj.2026.101175
Abstract
Inhibiting glycan degradation prevents HIV-induced inflammaging and cognitive impairment
People with HIV can develop problems with memory and cognition even when standard treatment keeps the virus under control. Understanding why this happens matters because these changes can reduce quality of life and may worsen with age.
This study found that people with HIV and cognitive problems had greater loss of protective sugar molecules on blood proteins, and this pattern was especially pronounced in women. In two mouse models, drugs that prevented the removal of these sugars reduced harmful inflammation, slowed aging-related changes, and prevented memory problems.
These findings suggest that these sugar molecules could help identify people at risk and that protecting them may offer a new approach for treating brain and aging-related complications linked to long-term viral infection.
