Multiple Sclerosis and Aging: The Dynamics of Demyelination and Remyelination.
Jorge CorrealeMaria Celica YsrraelitPublished in: ASN neuro (2022)
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) leading to demyelination and neurodegeneration. Life expectancy and age of onset in MS patients have been rising over the last decades, and previous studies have shown that age affects disease progression. Therefore, age appears as one of the most important factors in accumulating disability in MS patients. Indeed, the degeneration of oligodendrocytes (OGDs) and OGD precursors (OPCs) increases with age, in association with increased inflammatory activity of astrocytes and microglia. Similarly, age-related neuronal changes such as mitochondrial alterations, an increase in oxidative stress, and disrupted paranodal junctions can impact myelin integrity. Conversely, once myelination is complete, the long-term integrity of axons depends on OGD supply of energy. These alterations determine pathological myelin changes consisting of myelin outfolding, splitting, and accumulation of multilamellar fragments. Overall, these data demonstrate that old mature OGDs lose their ability to produce and maintain healthy myelin over time, to induce de novo myelination, and to remodel pre-existing myelinated axons that contribute to neural plasticity in the CNS. Furthermore, as observed in other tissues, aging induces a general decline in regenerative processes and, not surprisingly, progressively hinders remyelination in MS. In this context, this review will provide an overview of the current knowledge of age-related changes occurring in cells of the oligodendroglial lineage and how they impact myelin synthesis, axonal degeneration, and remyelination efficiency.
Keyphrases
- multiple sclerosis
- white matter
- oxidative stress
- end stage renal disease
- mass spectrometry
- ms ms
- induced apoptosis
- stem cells
- newly diagnosed
- chronic kidney disease
- ejection fraction
- prognostic factors
- gene expression
- dna damage
- peritoneal dialysis
- healthcare
- mesenchymal stem cells
- blood brain barrier
- cell therapy
- spinal cord
- electronic health record
- big data
- bone marrow
- brain injury
- endoplasmic reticulum stress
- data analysis
- functional connectivity