A UCSF study reveals that aging may actually ease lupus symptoms.
Immune overactivity in mid-life appears to diminish in older patients, reversing the usual age-related rise in inflammation and suggesting new treatment strategies.
Lupus: An Autoimmune Disease That Calms With Age
Lupus is considered one of the most well-known autoimmune diseases.
In people with lupus, the immune system’s frontline defense against viruses, called interferons, begins to mistakenly target the body itself. This internal attack can affect nearly every major organ, often leading to serious complications such as heart or kidney disease.
However, unlike many chronic or autoimmune conditions, lupus sometimes takes a surprising turn later in life. For some patients, symptoms may actually improve as they reach their 60s and 70s.
Real-World Clinical Observations
“I see my younger lupus patients in their 20s, 30s, and 40s every few months, monitoring them closely for signs of severe disease, but many of my older patients just once a year to touch base,” said Sarah Patterson, MD, assistant professor of medicine in the division of rheumatology at UCSF. “If patients make it through those risky decades, they sometimes see a dramatic improvement.”
Dr. Patterson and her team recently published new research in Science Translational Medicine that helps explain this age-related shift.
By examining blood samples from lupus patients of various ages, the researchers found that aging appears to reduce the activity of specific immune genes. This change results in lower levels of interferons and other proteins that drive inflammation throughout the body.
Inflammaging Reversed in Lupus Patients
The study found that in healthy adults, inflammation-related genes and proteins rose slowly over the years, a process that has been dubbed “inflammaging.” In patients with lupus, however, the expression of these genes and proteins were abnormally high in mid-life but decreased as the decades went by.
“Inflammaging seemed to be reversed in the lupus patients,” said Chaz Langelier, MD, PhD, associate professor of medicine at UCSF and senior author of the paper. “But it wasn’t fully reversed. The lupus patients still had a greater level of inflammatory signaling compared to healthy adults in older age.”
That reversal reflected what Patterson has seen in her patients — a return to something approaching healthy older age.
Hope for Broader Autoimmune Treatment
Next, the team intends to test whether drugs that block interferons are more or less effective in lupus patients at different ages. They also hope to extend the approach to understand other inflammation-related conditions, such as rheumatoid arthritis, COPD, and atherosclerosis.
Reference: “Epigenetic attenuation of interferon signaling is associated with aging-related improvements in systemic lupus erythematosus” by Rithwik Narendra, Hoang Van Phan, Sarah L. Patterson, Ana Almonte-Loya, Emily C. Lydon, Cristina Lanata, Christina Love, Joonsuk Park, Michiko Shimoda, Lisa Barcellos, Honey Mekonen, Angela Detweiler, Padmini Deosthale, Norma Neff, Lindsey A. Criswell, Lenka Maliskova, Walter Eckalbar, Gabriela K. Fragiadakis, Jinoos Yazdany, Maria Dall’Era, Patricia Katz, Chun Jimmie Ye, Marina Sirota and Charles R. Langelier, 25 June 2025, Science Translational Medicine.
DOI: 10.1126/scitranslmed.adt5550
Authors: Other UCSF authors are Rithwik Narendra, Hoang Van Phan, Ana Almonte-Loya, Emily C. Lydon, MD, Christina Love, Michiko Shimoda, PhD, Padmini Deosthale, MS, Lenka Maliskova, Walter Eckalbar, PhD, Gabriela K. Fragiadakis, PhD, Jinoos Yazdany, MD, MPH, Maria Dall’Era, MD, Patricia Katz, PhD, Chun Jimmie Ye, PhD, and Marina Sirota, PhD. For a complete author list see the paper.
Funding: This work was funded by the National Institutes of Health (R01 AR069616, K23AT011768, P30 AI027763), the US Centers for Disease Control and Prevention (CDC), and the Chan Zuckerberg Biohub.
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