The neural functions of adropin, a secreted peptide highly expressed in the brain, have not been investigated. In humans, adropin is highly expressed in astrocytes and peaks during critical postnatal periods of brain development. Gene enrichment analysis of transcripts correlating with adropin expression suggests processes relevant to aging-related neurodegenerative diseases that vary with age and dementia state, possibly indicating survivor bias. In people aged <40 y and ‘old-old’ (>75 y) diagnosed with dementia, adropin correlates positively with genes involved in mitochondrial processes. In the ‘old-old’ without dementia adropin expression correlates positively with morphogenesis and synapse function. Potent neurotrophic responses in primary cultured neurons are consistent with adropin supporting the development and function of neural networks. Adropin expression in the ‘old-old’ also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in those without dementia. How variation in brain adropin expression affects neurological aging was investigated using old (18-month) C57BL/6J mice. In mice adropin is expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia and shows correlative relationships with groups of genes involved in neurodegeneration and cellular metabolism. Increasing adropin expression using transgenesis improved spatial learning and memory, novel object recognition, resilience to exposure to new environments, and reduced mRNA markers of inflammation in old mice. Treatment with synthetic adropin peptide also reversed age-related declines in cognitive functions and affected expression of genes involved in morphogenesis and cellular metabolism. Collectively, these results establish a link between adropin expression and neural energy metabolism and indicate a potential therapy against neurological aging.

adropin 是一种在大脑中高度表达的分泌肽，其神经功能尚未得到研究。在人类中，adropin 在星形胶质细胞中高度表达，并在大脑发育的关键出生后时期达到峰值。与 adropin 表达相关的转录本的基因富集分析表明与衰老相关的神经退行性疾病相关的过程随年龄和痴呆状态而变化，可能表明幸存者偏差。在被诊断患有痴呆症的年龄 <40 岁和“老年人”（> 75 岁）的人群中，adropin 与参与线粒体过程的基因呈正相关。在没有痴呆症的“老人”中，adropin 表达与形态发生和突触功能呈正相关。原代培养神经元中的有效神经营养反应与支持神经网络发育和功能的 adropin 一致。“老人”中的 Adropin 表达也与 tau 相关神经病理学和炎症的蛋白质标志物呈正相关，特别是在那些没有痴呆症的人中。使用旧的（18 个月）C57BL/6J 小鼠研究了脑 adropin 表达的变化如何影响神经衰老。在小鼠中，adropin 在神经元、少突胶质祖细胞、少突胶质细胞和小胶质细胞中表达，并与参与神经变性和细胞代谢的基因组显示相关关系。使用转基因增加 adropin 表达改善空间学习和记忆、新物体识别、暴露于新环境的弹性、并减少老年小鼠炎症的 mRNA 标志物。用合成的 adropin 肽治疗还可以逆转与年龄相关的认知功能下降，并影响参与形态发生和细胞代谢的基因的表达。总的来说，这些结果建立了 adropin 表达和神经能量代谢之间的联系，并表明了一种对抗神经衰老的潜在疗法。