Immune aging in people with multiple sclerosis: new insights from a comprehensive characterization
Year: 2025
Type: dissertation
Study design: Observational Study
Abstract: Multiple Sclerosis (MS) is a chronic, inflammatory, and neurodegenerative disorder, typically diagnosed in youngadulthood. Advances in healthcare and the introduction of effective therapies have increased life expectancy ofpeople with MS, resulting in nearly one-quarter of MS population being over the age of 65. This places aging,specially immune aging, as a determinant factor in the disease. A deeper understanding of its biological interplay isessential for MS management. This thesis performs a comprehensive characterization of aging in people with MS,integrating immunological, metabolic, neurodegenerative, and transcriptomic perspectives. Immunologicalanalysis revealed disease-specific alterations in immune cell populations with age. People with MS showed increasedactivated T subsets and distinct age-related patterns in T helper and cytotoxic cells, with activated and senescent Tcells increasing with age. We observed an earlier onset of thymic involution in MS, evidenced by reduced sjTRECcontent in young individuals. Furthermore, people with MS exhibited a pro-inflammatory profile with elevated IL6, TNF-¿, and IL-10, and age-dependent increases in IL-6, CRP, and TNF-¿ not seen in healthy controls. Regardingmetabolic and neurodegenerative markers, NFL was elevated in MS even at younger ages, indicating early neuronaldamage. We also observed signs of compromised mitochondrial maintenance, including age-dependent decreasesin mtDNA and ATP production in the MS group. Finally, transcriptomic analyses showed that physiological agingpatterns were altered in MS. We found profound age-specific alterations in gene and miRNA expression in MS, withminimal overlap between younger and older individuals. In conclusion, aging in MS is not simply accelerated, but acomplex, systemic, and dynamic process where chronic inflammation and immune dysregulation continuouslyinteract. This framework is essential to develop more precise, age-adapted strategies to improve outcomes forpeople with MS as they grow older
Author: Iribarren López, Andrea
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7134145902