Erraji-Benchekroun Loubna, Underwood Mark D, Arango Victoria, Galfalvy Hanga, Pavlidis Paul, Smyrniotopoulos Peggy, Mann J John, Sibille Etienne
Department of Psychiatry, Columbia University, New York, New York, USA.
Biol Psychiatry. 2005 Mar 1;57(5):549-58. doi: 10.1016/j.biopsych.2004.10.034.
Aging leads to morphologic and functional changes in the brain and is associated with increased risk for psychiatric and neurological disorders.
To identify age-related transcriptional changes in the human brain, we profiled gene expression in two prefrontal cortex (PFC) areas in postmortem samples from 39 subjects, ranging in age from 13 to 79 years.
Robust transcriptional age-related changes were identified for at least 540 genes. Gene expression correlates of aging were highly specific, and the large majority of the 22,000 transcripts investigated were unaffected by age. Across subjects, changes were progressive throughout adult life and accurately predicted chronological age. Age-upregulated transcripts were mostly of glial origin and related to inflammation and cellular defenses, whereas downregulated genes displayed mostly neuron-enriched transcripts relating to cellular communication and signaling.
Continuous changes in gene expression with increasing age revealed a "molecular profile" of aging in human PFC. The restricted scope of the transcript changes suggests cellular populations or functions that are selectively vulnerable during aging. Because age-related gene expression changes begin early in adulthood and are continuous throughout life, our results suggest the possibility of identifying early cellular mechanisms that may be engaged in preventive or detrimental age-related brain functions.
衰老会导致大脑出现形态和功能变化，并与精神和神经疾病风险增加相关。
为了识别与年龄相关的人类大脑转录变化，我们对39名年龄在13至79岁之间的受试者的死后样本中两个前额叶皮质（PFC）区域的基因表达进行了分析。
至少540个基因被鉴定出与年龄相关的强大转录变化。衰老的基因表达相关性具有高度特异性，在研究的22000个转录本中，绝大多数不受年龄影响。在所有受试者中，这些变化在成年期是渐进的，并且能准确预测实际年龄。随年龄上调的转录本大多起源于胶质细胞，与炎症和细胞防御相关，而下调的基因大多显示与细胞通讯和信号传导相关的富含神经元的转录本。
随着年龄增长基因表达的持续变化揭示了人类PFC衰老的“分子特征”。转录本变化的有限范围表明了在衰老过程中选择性易损的细胞群体或功能。由于与年龄相关的基因表达变化在成年早期就开始并贯穿一生，我们的结果表明有可能识别出可能参与与年龄相关的大脑预防或有害功能的早期细胞机制。
