Fraser Hunter B, Khaitovich Philipp, Plotkin Joshua B, Pääbo Svante, Eisen Michael B
Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.
PLoS Biol. 2005 Sep;3(9):e274. doi: 10.1371/journal.pbio.0030274. Epub 2005 Aug 2.
It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.
众所周知,许多生物体中的基因表达水平在衰老过程中会发生变化,而DNA微阵列技术的出现使得在模式生物和各种人体组织中研究与衰老相关的全基因组转录变化模式成为可能。由于衰老与正常和病理性神经退行性变都有关系,因此了解衰老对人类大脑基因表达的影响尤为重要。在这里,我们表明人类大脑皮层、人类小脑和黑猩猩皮层各自经历了与年龄相关的不同基因表达变化模式。在人类中,与小脑相比,大脑皮层中有更多基因经历一致的表达变化;在黑猩猩中,许多基因在皮层中随年龄变化表达,但表达变化模式与人类皮层几乎没有相似之处。这些结果证明了人类大脑中存在的衰老模式的多样性,以及全基因组衰老模式在物种间进化的速度有多快;它们也可能对衰老的氧化自由基理论有影响,并有助于提高我们对人类神经退行性疾病的理解。