在老化的人类大脑中,基因调节和DNA损伤
Tao Lu1, Ying Pan, Shyan-Yuan Kao
1Department of Neurology and Division of Neuroscience, The Children's Hospital and Harvard Medical School, Enders 260,300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nature
|June 11, 2004
概括
大脑衰老是认知能力下降的一个原因,在成年早期就开始了. 40岁后前额皮质的特定基因表达变化和DNA损伤表明这个过程的开始.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 衰老研究研究 衰老研究
背景情况:
- 人类大脑衰老与认知能力下降和阿尔茨海默病有关.
- 大脑衰老的确切开始仍未确定.
- 识别早期的分子变化对于理解与年龄相关的认知障碍至关重要.
研究的目的:
- 为了确定大脑衰老何时开始.
- 为了识别与早期大脑衰老相关的分子标记.
- 为了研究DNA损伤在与年龄相关的基因表达变化中的作用.
主要方法:
- 在广泛的年龄范围 (26-106岁) 中,对人类前额皮层的转录概况.
- 分析与突触可塑性,线粒体功能和应激反应相关的基因表达模式.
- 评估特定基因促进体中的DNA损伤和修复机制.
主要成果:
- 一组参与突触可塑性,囊泡运输和线粒体功能的基因在40岁后表达减少.
- 这种下降随后引发了应激反应,抗氧化剂和DNA修复基因.
- 在老年皮质中,下调基因的促进者中观察到DNA损伤的增加,并且基础切割修复受损.
结论:
- 大脑衰老的特征是特定的基因表达变化和DNA损伤,在成年早期开始.
- DNA 损伤可能会选择性地减少对学习,记忆和神经元生存至关重要的基因的表达.
- 这些发现表明,大脑衰老的分子程序从成年期中期开始.
相关概念视频
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Neural Regulation
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
Overview of DNA Repair
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
The Effect of Aging on Tissues
Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...
Aging
Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...


