“The loss of myelin due to aging or neurodegenerative diseases has profound consequences for neurological functions.”
“The study was co‑led by ISABIAL and Institute of Neurosciences Miguel Servet researcher Alerie Guzmán, together with Denise Fitzgerald from Queen’s University Belfast (United Kingdom).”
“Alicante (03.11.21). A study has shown that aging reduces the ability of regulatory T lymphocyte cells to enhance the regeneration of myelin, the fatty layer that surrounds nerve fibers. The research, published in the journal Nature Communications, was co‑led by Alerie Guzmán, Miguel Servet researcher at the Alicante Institute for Health and Biomedical Research (ISABIAL) and the Institute of Neurosciences (IN), a joint center of the Spanish National Research Council (CSIC) and Miguel Hernández University (UMH) of Elche.”
“Regulatory T lymphocytes are cells responsible for regulating the immune system and have regenerative functions in several contexts, including the process of myelin repair. To determine whether the function of these lymphocytes is impaired by aging, Alerie Guzmán co‑led a study with Denise Fitzgerald from Queen’s University Belfast (United Kingdom), showing that although the number of regulatory T lymphocytes increases with age, their ability to promote the differentiation of oligodendrocyte progenitor cells (OPCs) into new cells that replace lost myelin is reduced. OPCs are the cells that form the myelin sheath in the brain and spinal cord.”
“Myelin is a protective substance in the nervous system that surrounds nerve fibers, allowing communication between neurons to occur quickly and efficiently. Researcher Alerie Guzmán explained that it is ‘equivalent to the plastic coating around copper in a cable,’ noting that the loss of myelin due to aging or neurodegenerative diseases such as multiple sclerosis has profound consequences for neurological functions. In this study, the researchers focused on how aging—a key risk factor that limits myelin regeneration—affects the functioning of regulatory T lymphocytes in the brain and spinal cord.”
“Myelin is a protective substance in the nervous system that surrounds nerve fibers, allowing communication between neurons to occur quickly and efficiently. Researcher Alerie Guzmán explained that myelin ‘is equivalent to the plastic coating around copper in a cable,’ while noting that its loss due to aging or neurodegenerative diseases such as multiple sclerosis has profound consequences for neurological functions. In this study, the researchers focused on how aging—a key risk factor that limits myelin regeneration—affects the functioning of regulatory T lymphocytes in the brain and spinal cord.”
“To carry out this study, the researchers used an animal model of mice aged between 19 and 23 months, which corresponds approximately to 65–70 years in humans. The team observed that the presence of regulatory T lymphocytes increases with aging; however, these cells had lost their ability to enhance the conversion of OPCs into new oligodendrocytes that regenerate myelin when damage occurs.”
“Reversible in a young environment”
“The researchers wanted to determine whether this loss of regulatory T‑cell function was completely irreversible. To do so, they conducted several experiments in young mice whose own cells were replaced with aged regulatory T lymphocytes. They found that, in a young animal, both young and old cells have the same ability to enhance myelin regeneration.”
“The results of these experiments, which also involved ISABIAL and Institute of Neurosciences CSIC‑UMH researchers Sonia Cabeza Fernández and Francisco Javier Rodríguez Baena, together with a team from the University of Cambridge (United Kingdom), Altos Laboratories (United Kingdom), and the University of Southern Denmark, are highly positive, as they suggest that the loss of this function may be reversible.”
“New avenues of research”
“Researcher Alerie Guzmán noted that ‘regulatory T lymphocytes are very complex because they modulate immune system functions, and in patients it is not feasible to eliminate them in order to replace them with young cells.’ She also explained that ‘the aim was to identify some of the mechanisms involved in age‑related dysfunction so that they can be modulated in a more targeted way.’”
“Using a series of techniques, including transcriptomic analysis, the researchers identified two new molecules involved in this process. Transcriptomics is the study of all RNA molecules within a cell. The two newly identified molecules involved in this process are Integrin alpha 2 (ITGA2) and Melanoma Cell Adhesion Molecule (MCAM).”
“The researchers found that both molecules not only decrease with aging in regulatory T lymphocytes, but are also involved in the interaction between these lymphocytes and the progenitor stem cells that regenerate myelin, the OPCs.”
“This finding opens new avenues of research to determine whether the molecules mentioned above have potential as therapeutic targets. Further studies are needed to establish whether manipulating these proteins could enhance myelin regeneration in older patients with multiple sclerosis.”
“This work was made possible thanks to funding from the Wellcome Trust (United Kingdom); the Biotechnology and Biological Sciences Research Council (BBSRC) of UK Research and Innovation (UKRI); the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); the Miguel Servet fellowship program of the Instituto de Salud Carlos III; the 2021 State Plan for Knowledge Generation of the Spanish State Research Agency–Ministry of Science, Innovation and Universities; the Generalitat Valenciana; the Leverhulme Trust (United Kingdom); and the Department for the Economy of Northern Ireland.”
