Oligodendrocytes in the aging brain

Abstract

More than half of the human brain volume is made up of white matter: regions where axons are coated in myelin, which primarily functions to increase the conduction speed of axon potentials. White matter volume significantly decreases with age, correlating with cognitive decline. Much research in the field of non-pathological brain aging mechanisms has taken a neuron-centric approach, with relatively little attention paid to other neural cells. This review discusses white matter changes, with focus on oligodendrocyte lineage cells and their ability to produce and maintain myelin to support normal brain homeostasis. Improved understanding of intrinsic cellular changes, general senescence mechanisms, intercellular interactions and alterations in extracellular environment which occur with aging and impact oligodendrocyte cells is paramount. This may lead to strategies to support oligodendrocytes in aging, for example by supporting myelin synthesis, protecting against oxidative stress and promoting the rejuvenation of the intrinsic regenerative potential of progenitor cells. Ultimately, this will enable the protection of white matter integrity thus protecting cognitive function into the later years of life.

Replenishing the Aged Brains: Targeting Oligodendrocytes and Myelination?

“…These changes may be detrimental to OPC differentiation and myelin formation in the aged brain. Besides, other factors, including oxidative stress induced by vascular changes during aging and deregulation of glutamate neurotransmission in the aged brains may also play roles in age-related myelinogenesis decline ( Rivera et al, 2016 ; Bagi et al, 2018 ; Bors et al, 2018 ; Sams, 2021 ; Summarized in Figure 1 ).…”

“…For example, it was reported that OLs occupy about 75% of all glial cells in the neocortex of human brain (von Bartheld et al, 2016). More importantly, oligodendroglia lineage cells are undergoing dynamic changes during aging and that have been extensively reported recently (Stadelmann et al, 2019;Chapman and Hill, 2020;Sams, 2021).…”

Age-Related Midbrain Inflammation and Senescence in Parkinson’s Disease

“…Cellular senescence is apparent in astrocytes, microglia, and neurons of the midbrain which are neighbors to oligodendrocytes. There is accumulating evidence of senescencelike features in oligodendrocytes and their progenitors (Sams, 2021) with increasing age, but a clear demonstration of oligodendrocyte senescence in PD has yet to be shown. Senescence of oligodendrocytes has been reported in white matter lesions which are common in brain aging and are associated with dementia (Al-Mashhadi et al, 2015).…”

Role of the MBP protein in myelin formation and degradation in the brain

“…Under the microscope, age-related degenerative abnormalities in myelin sheaths are revealed as myelin balloons (Feldman and Peters, 1998) and splits of the lamellae at the major dense line (Peters, 2002). Reasons for this are not clear, however, this could be a consequence of a complex of factors, such as reduced OPC differentiation (Sim, Zhao, Penderis and Franklin, 2002), differential vulnerability of oligodendrocytes to accumulation of DNA damage and oxidative stress (Tse and Herrup, 2017), altered lipid metabolism (Lefèvre-Arbogast et al, 2021), and decreased nutrient and energy availability for myelinating cells (Sams, 2021). In addition, senescence-dependent abnormalities in myelin are often caused by a decrease in the expression level of various genes, including MBP, which serves as a robust indicator of brain age.…”