Age-associated cognitive decline is common among otherwise healthy elderly people, even in the absence of Alzheimer’s disease and neuron loss. Instead, white matter loss and myelin damage are strongly associated with cognitive decline. Myelin is subject to lifelong oxidative stress that damages the myelin sheath, which is repaired by cells of the oligodendrocyte lineage. This process is mediated by oligodendrocyte precursor cells (OPCs) that sense the damage and respond by proliferating locally and migrating to the region, where they differentiate into mature myelinating oligodendrocytes. In aging, extensive myelin damage, in combination with inefficient remyelination, leads to chronically damaged myelin and loss of efficient neuronal conduction. This study used the rhesus monkey model of normal aging to examine how myelin regeneration capacity is affected by age. Results show that older subjects have reduced numbers of new BCAS1 + myelinating oligodendrocytes, which are newly formed cells, and that this reduction is associated with poorer cognitive performance. Interestingly, this does not result from limited proliferation of progenitor OPCs. Instead, the transcription factor NKX2.2, which regulates OPCs differentiation, is significantly decreased in aged OPCs. This suggests that these OPCs have a diminished potential for differentiation into mature oligodendrocytes. In addition, mature oligodendrocytes have reduced RNA expression of two essential myelin protein markers, MBP and PLP. These data collectively suggest that in the normal aging brain, there is a reduction in regenerative OPCs as well as myelin production that impairs the capacity for remyelination.

即使没有阿尔茨海默病和神经元损失，与年龄相关的认知能力下降在其他方面健康的老年人中也很常见。相反，白质损失和髓磷脂损伤与认知能力下降密切相关。髓磷脂终生受到氧化应激的影响，从而损害髓鞘，而髓鞘由少突胶质细胞谱系的细胞修复。这一过程由少突胶质细胞前体细胞 (OPC) 介导，少突胶质细胞前体细胞感知损伤并通过局部增殖和迁移到该区域做出反应，并在该区域分化为成熟的髓鞘少突胶质细胞。在衰老过程中，广泛的髓磷脂损伤加上髓鞘再生效率低下，会导致髓磷脂慢性受损和有效神经元传导的丧失。这项研究使用正常衰老的恒河猴模型来研究年龄对髓磷脂再生能力的影响。结果表明，老年受试者的新 BCAS1 + 髓鞘少突胶质细胞（新形成的细胞）数量减少，并且这种减少与较差的认知能力相关。有趣的是，这并不是由于祖细胞 OPC 增殖有限所致。相反，调节 OPC 分化的转录因子 NKX2.2 在衰老的 OPC 中显着减少。这表明这些 OPC 分化为成熟少突胶质细胞的潜力减弱。此外，成熟的少突胶质细胞降低了两种必需髓磷脂蛋白标记物 MBP 和 PLP 的 RNA 表达。这些数据共同表明，在正常衰老的大脑中，再生原花青素和髓鞘质的生成都会减少，从而损害髓鞘再生的能力。