Disease Aggravation With Age in an Experimental Model of Multiple Sclerosis : Role of Immunosenescence
Dema, María (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Eixarch, Herena (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Hervera Abad, Arnau (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Castillo Juárez, Mireia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Villar, Luisa M (Hospital Universitario Ramón y Cajal (Madrid))
Montalban, Xavier (Universitat Autònoma de Barcelona. Departament de Medicina)
Espejo, Carmen (Hospital Universitari Vall d'Hebron. Institut de Recerca)

Publicació:	2025 2025
Descripció:	22 pàg.
Resum:	The onset of multiple sclerosis (MS) in older individuals correlates with a higher risk of developing primary progressive MS, faster progression to secondary progressive MS, and increased disability accumulation. This phenomenon can be related to age-related changes in the immune system: with age, the immune system undergoes a process called immunosenescence, characterized by a decline in the function of both the innate and adaptive immune responses. This decline can lead to a decreased ability to control inflammation and repair damaged tissue. Additionally, older individuals often experience a shift toward a more pro-inflammatory state, known as inflammaging, which can exacerbate the progression of neurodegenerative diseases like MS. Therefore, age-related alterations in the immune system could be responsible for the difference in the phenotype of MS observed in older and younger patients. In this study, we investigated the effects of age on the immunopathogenesis of experimental autoimmune encephalomyelitis (EAE). Our findings indicate that EAE is more severe in aged mice due to a more inflammatory and neurodegenerative environment in the central nervous system. Age-related changes predominantly affect adaptive immunity, characterized by altered T cell ratios, a pro-inflammatory Th1 response, increased regulatory T cells, exhaustion of T cells, altered B cell antigen presentation, and reduced NK cell maturation and cytotoxicity. Transcriptomic analysis reveals that fewer pathways and transcription factors are activated with age in EAE. These findings allow us to identify potential therapeutic targets specific to elderly MS patients and work on their development in the future.
Ajuts:	Instituto de Salud Carlos III PI18/01146 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00782
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Adaptive immunity ; Aging ; Experimental autoimmune encephalomyelitis ; Immunosenescence ; Innate immunity ; Multiple sclerosis ; Neurodegeneration ; Neuroinflammation
Publicat a:	Aging Cell, 2025 , ISSN 1474-9726

DOI: 10.1111/acel.14491
PMID: 39894902

22 p, 6.9 MB

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