Peroxisomes exist in nearly every cell, oxidizing fats, synthesizing lipids and maintaining redox balance. As the brain ages, multiple pathways are negatively affected, but it is currently unknown if peroxisomal proteins are affected by aging in the brain. While recent studies have investigated a PEX5 homolog in aging C. elegans models and found that it is reduced in aging, it is unclear if PEX5, a mammalian peroxisomal protein that plays a role in peroxisomal homeostasis and degradation, is affected in the aging brain. To answer this question, we first determined the amount of PEX5, in brain homogenates from young (3 months) and aged (26 through 32+ months of age) wild-type mice of both sexes. PEX5 protein was decreased in aged male brains, but this reduction was not significant in female brains. RNAScope and real-time qPCR analyses showed that Pex5 mRNA was also reduced in aged male brain cortices, but not in females. Immunohistochemistry assays of cortical neurons in young and aged male brains showed that the amount of neuronal PEX5 was reduced in aged male brains. Cortical neurons in aged female mice also had reduced PEX5 levels in comparison to younger female mice. In conclusion, total PEX5 levels and Pex5 gene expression both decrease with age in male brains, and neuronal PEX5 levels lower in an age-dependent manner in the cortices of animals of both sexes.

过氧化物酶体几乎存在于每个细胞中，氧化脂肪、合成脂质并维持氧化还原平衡。随着大脑老化，多种通路受到负面影响，但目前尚不清楚过氧化物酶体蛋白是否受到大脑老化的影响。虽然最近的研究调查了衰老线虫模型中的 PEX5 同源物，发现它在衰老过程中减少，但尚不清楚 PEX5（一种在过氧化物酶体稳态和降解中发挥作用的哺乳动物过氧化物酶体蛋白）是否在衰老的大脑中受到影响。为了回答这个问题，我们首先测定了年轻（3个月）和老年（26至32个月以上）野生型两性小鼠脑匀浆中PEX5的含量。PEX5 蛋白在老年男性大脑中减少，但这种减少在女性大脑中并不显着。RNAScope 和实时 qPCR 分析表明，老年男性大脑皮质中的Pex5 mRNA 也有所减少，但女性中则没有。对年轻和老年男性大脑皮质神经元的免疫组织化学分析表明，老年男性大脑中神经元 PEX5 的数量减少。与年轻雌性小鼠相比，老年雌性小鼠的皮质神经元 PEX5 水平也有所降低。总之，男性大脑中总 PEX5 水平和Pex5基因表达均随着年龄的增长而降低，并且两性动物皮质中神经元 PEX5 水平以年龄依赖性方式降低。