Calorie restriction (CR) is a robust intervention that can slow biological aging and extend lifespan. In the brain, terminally differentiated neurons and glia accumulate oxidative damage with age, reducing their optimal function. We investigated if CR could reduce oxidative DNA damage to white matter oligodendrocytes and microglia. This study utilized post-mortem brain tissue from rhesus monkeys that died after decades on a 30 % reduced calorie diet. We found that CR subjects had significantly fewer cells with oxidative damage within the corpus callosum and the cingulum bundle. Oligodendrocytes specifically showed the greatest response to CR with a robust reduction in DNA damage. Additionally, we observed alterations in microglia morphology with CR subjects having a higher proportion of ramified, homeostatic microglia and fewer pro-inflammatory, hypertrophic microglia relative to controls. Furthermore, we determined that the observed attenuation in damaged DNA occurs primarily within mitochondria. Overall, these data suggest that long-term CR can reduce oxidative DNA damage and offer a neuroprotective effect in a cell-type-specific manner in the aging monkey brain.

中文翻译：

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长期热量限制可减少对少突胶质细胞的氧化DNA损伤，并促进衰老猴脑中小胶质细胞的稳态


热量限制（CR）是一种强有力的干预措施，可以减缓生物衰老并延长寿命。在大脑中，终末分化的神经元和神经胶质细胞随着年龄的增长而积累氧化损伤，从而降低其最佳功能。我们研究了 CR 是否可以减少白质少突胶质细胞和小胶质细胞的氧化 DNA 损伤。这项研究利用了恒河猴的死后脑组织，这些恒河猴在摄入减少 30% 热量的饮食几十年后死亡。我们发现 CR 受试者胼胝体和扣带束内发生氧化损伤的细胞明显较少。少突胶质细胞特别表现出对 CR 的最大反应，DNA 损伤显着减少。此外，我们观察到与对照组相比，CR 受试者的小胶质细胞形态发生变化，其分支、稳态小胶质细胞比例更高，促炎、肥大小胶质细胞比例更少。此外，我们确定观察到的受损 DNA 的衰减主要发生在线粒体内。总体而言，这些数据表明，长期 CR 可以减少氧化 DNA 损伤，并以细胞类型特异性的方式在衰老猴脑中提供神经保护作用。