Aging Cell：女性大脑中前额皮层区域可加速衰老

国际知名杂志Aging Cell于8月2日在线发表了计算生物学所研究人员研究表明，女性呈现出更快的和年龄相关的认知衰退和较高的阿尔兹海默病的发病率，这与女性的平均寿命通常比男性长似乎矛盾。

计算生物学所袁媛和Mehmet博士对成年男性和女性大脑中的四个区域随年龄变化的表达差异进行了分析。结果显示，在前额皮层中的额上回区域，两性在年龄相关的变化时机上存在着明显差异，这也被称为两性发育的异时性。

有趣的是，女性相对男性来说，与年龄相关的表达变化差异发生的更早或发生的更快。这些变化富集在能量产生下降和神经功能，上调免疫反应和大脑衰老的主要功能。此外，研究发现女性大脑中部分基因的加速表达变化和阿尔兹海默病的表达变化相关，同时也和承受外界的压力效应相关。

分析结果提示，女性对压力的反应更为敏感，终身暴露在较高的压力水平下，可能会永久导致女性大脑的转录组呈现出衰老及阿尔兹海默病的状态。

该研究获得国家科技部、中国科学院、上海生命科学研究院、德国马普学会、德国联邦教育与研究部的经费资助。

doi:10.1111/j.1474-9726.2012.00859.x
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Accelerated aging-related transcriptome changes in the female prefrontal cortex

Yuan Yuan1,2, Yi-Ping Phoebe Chen2, Jerome Boyd-Kirkup1, Philipp Khaitovich1,3, Mehmet Somel1,3,4

Human female life expectancy is higher than that of males. Intriguingly, it has been reported that women display faster rates of age-related cognitive decline and a higher prevalence of Alzheimer’s disease (AD). To assess the molecular bases of these contradictory trends, we analyzed differences in expression changes with age between adult males and females, in four brain regions. In the superior frontal gyrus (SFG), a part of the prefrontal cortex, we observed manifest differences between the two sexes in the timing of age-related changes, that is, sexual heterochrony. Intriguingly, age-related expression changes predominantly occurred earlier, or at a faster pace, in females compared to men. These changes included decreased energy production and neural function and up-regulation of the immune response, all major features of brain aging. Furthermore, we found that accelerated expression changes in the female SFG correlated with expression changes observed in AD, as well as stress effects in the frontal cortex. Accelerated aging-related changes in the female SFG transcriptome may provide a link between a higher stress exposure or sensitivity in women and the higher prevalence of AD.