Myelin is an insulator that sheaths the axons forming nervous system connections. It is essential to the correct electrochemical function of the nervous system. Severe conditions such as multiple sclerosis result when myelin is lost, degrading nervous system function to the point of disability and death.
In normal aging, myelin is also lost, though to a lesser degree. It is reasonable to think that this contributes to neurodegeneration and cognitive decline, but the only straightforward way to determine the relative importance of demyelination versus the many other mechanisms at work in the aging brain is to fix the problem in isolation and observe the results.
Like all structures in the body, myelin must be constantly maintained by a dedicated hierarchy of specialized cells. In this case, this means oligodendrocytes and their precursors. Significant disruption of this population results in demyelination. There is a good deal of evidence to suggest that oligodendrocytes are negatively affected by mechanisms of aging, such as the growing chronic inflammation provoked by the secretions of senescent cells. The population diminishes in size and undergoes changes in behavior. Thus strategies focused on restoration of oligodendrocyte populations via cell therapy, or at least the restoration of their youthful behavior via suitable delivery of signals, may be a good approach to restoring lost myelin and evaluating contribution of demyelination to cognitive aging.
Replenishing the Aged Brains: Targeting Oligodendrocytes and Myelination?
Age-related neurofunctional decline may negatively impact the daily life for the elderly, and no effective strategies are available so far in the clinic. This present review mainly focuses on myelin degeneration, decreased myelinogenesis during aging, and the possible mechanisms. Admittedly, a lot of questions remain unanswered. For instance, are there spatial or temporal differences in the degeneration process in the central nervous system (CNS)? What is the deciding point for one oligodendrocyte (OL) or one myelin segment to initiate degeneration and could we inhibit this bad process through modulating one key factor? Is the newly generated myelin more stable compared to preexisting myelin in the aged brain? If this is the case, we may find some clues about repressing myelin degeneration in the aged. The decreased myelinogenesis during aging is likely a result of arrested differentiation of oligodendroglia precursor cells (OPCs), thus it is plausible that promoting adult OPCs maturation may be a feasible and realistic approach to improve age-related neuronal function decline for the elderly. Meanwhile, rejuvenating subventricular zone (SVZ) stem cells may also help with myelinogenesis ability in the aged. More efforts are needed to further confirm those effects in human.
Moreover, oligodendroglial lineage cells display more behaviors than differentiation and forming new myelin sheaths. For example, OPCs may form synaptic connections with neighboring neurons, and that regulates neuronal signals in the CNS. In addition, the expression of connexin channel proteins in oligodendroglial lineage cells is an intriguing feature and the connexins could function either as hemichannels or gap junctions. The gap junction enables OLs to be connected as a glial network with astrocytes, allowing transportation of small molecules such as calcium and energy metabolites, which may be important for homeostasis of the CNS. Recent studies even showed that OPCs could exert immunomodulatory functions, which are particularly relevant in the context of neurodegeneration and demyelinating diseases. Besides, OLs are found to be heterogenetic in the mouse juvenile and adult CNS, the response of different subtypes to aging remains unknown. It is not clear whether the functions mentioned above and their correspondent molecules are altered during aging. Future works are needed to give us a more comprehensive understanding of the role oligodendroglial lineage cells played in aged brains, which could shed light on the clinical therapeutic strategies considering age-related neuronal functional diseases.
Source: Fight Aging!
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