Researchers from University of California San Diego School of Medicine have discovered that children living with multiple sclerosis (MS) show signs of accelerated biological aging, even in their teenage years. The research published online recently in Neurology®, the medical journal of the American Academy of Neurology, is the first to examine whether MS causes early aging in a pediatric population — offering new insight into the disease and its long-term progression.
"We found evidence that children living with MS experience accelerated biological aging," said Jennifer S. Graves, M.D., Ph.D., senior author of the study, professor and vice chair of neurosciences and division chief of neuroimmunology at UC San Diego. "Compared to young people without MS, youth with MS had evidence of accelerated epigenetic age, a measurement of DNA chemical modifications associated with aging. We know that aging is related to the development of a less treatable form of MS and that adults with MS face both normal aging and accelerated aging from the disease."
MS is a lifelong autoimmune disease that attacks the brain, spinal cord and optic nerves. The research team used DNA methylation markers — molecular changes that indicate biological age — to analyze blood samples from 125 children with MS and 145 children without MS. In contrast to chronological age, which reflects the number of birthdays, biological age tracks how quickly the body is wearing down on a cellular level.
The study focused on children and teenagers not yet impacted by the processes of normal aging and age-related illnesses like hypertension and diabetes. Despite appearing outwardly healthy, children with MS showed DNA patterns indicating they were biologically older than their peers.
The researchers found differences in four different epigenetic clocks and signs of accelerated aging in MS patients in models of two clocks most sensitive to health-related stress and inflammation. Epigenetic clocks are age-predicting algorithms that calculate epigenetic age as an estimate of chronological age or age-associated clinical events such as disease or all-cause mortality. The most affected kids appeared to be aging up to two years faster biologically than their healthy peers, even though their average chronological age was just 15.
Biological age has already been linked to disability progression in adults with MS. This study suggests the process may start much earlier than previously thought, potentially even before visible symptoms of progression appear. And that could change the way MS is treated.
"This is a whole new concept in MS," said Graves. "Aging isn't something we think of affecting teenagers. But these kids are accumulating cellular damage that may not show up clinically until years later, when they suddenly transition from doing fine to disease progression in their 30s. It is a significant finding to see this accelerated aging in children. If we can understand the interplay between the immune system, the brain and aging — and break that open — we might be able to put MS into full remission in the future."
The researchers hope future studies will track patients over time to see how early biological aging contributes to long-term disability. They also plan to explore how social stressors, obesity and environmental exposures may accelerate aging in children with MS, especially given the higher prevalence of pediatric MS among lower-income families.
Additional co-authors on the study include: Christopher Goyne, M.D. and Ashley Fair at UC San Diego; Defne Yilmaz, M.S. and Lisa F. Barcellos, Ph.D. at UC Berkeley; Jonathan Race, Ph.D., Allison Schuette, M.S., T. Charles Casper, Ph.D. at University of Utah; Stacy Caillier, John Rose, M.D. and Emmanuelle L. Waubant, M.D., Ph.D. from UCSF; Gregory Aaen, M.D. from Loma Linda University; Aaron Abrams, M.D. and Mary R. Rensel, M.D. from the Cleveland Clinic; Leslie Benson, M.D., Tanuja Chitnis, M.D. and Mark Gorman, Ph.D. from Brigham and Women's Hospital; Timothy Lotze, M.D. from Texas Children's Hospital; Lauren Krupp, M.D. from NYU Langone Multiple Sclerosis Comprehensive Care Center; Soe Mar, M.D. from Washington University in St. Louis; Jayne Ness, M.D. Ph.D. from The University of Alabama at Birmingham; Manuel Rodriguez, M.D, Jan-Mendelt Tillema, M.D. and Yolanda Wheeler, Ph.D., from the Mayo Clinic; Teri Schreiner, M.D. from University of Colorado; and Amy T. Waldman from Children's Hospital of Philadelphia.
The study was funded, in part, by the National Institutes of Health (R01NS071463) and National MS Society (RG-19707-34664 and RG-2207-39976).
