减少MYC的表达增加了寿命,并增强了健康的发展
Jeffrey W Hofmann1, Xiaoai Zhao1, Marco De Cecco1
1Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA.
Cell
|January 27, 2015
概括
在小鼠中降低MYC (Myc原型瘤基因) 水平可以延长寿命并改善健康寿命. 缺乏氨酸的Myc小鼠对与年龄相关的疾病具有抗性,并增强了新陈代谢和免疫功能.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 衰老研究研究 衰老研究
背景情况:
- MYC原基因是细胞增殖,新陈代谢和亡的关键调节者.
- 在各种癌症中经常观察到MYC放松调节,推动瘤发生.
- 它在衰老和长寿中的作用仍然不完全理解.
研究的目的:
- 调查MYC水平降低对寿命和与年龄相关的疾病的影响.
- 探索与MYC平分不充分性相关的潜在长寿益处背后的分子机制.
- 评估对老年小鼠代谢和免疫功能的影响.
主要方法:
- 产生和分析Myc哈普洛因不足 (Myc(+/-)) 的小鼠.
- 评估寿命,与年龄相关的疾病 (骨质疏松症,心脏纤维化,免疫衰退),身体活动和代谢率.
- 转录组分析以识别基因表达特征.
- 测量蛋白质翻译速率和关键营养/能量感知通路 (IGF-1,AMPK,AKT,TOR,S6K).
主要成果:
- 与野生类型对照相比,Myc(+/-) 鼠的寿命显著增加.
- 这些小鼠表现出对骨质疏松症,心脏纤维化和免疫衰变的抵抗力.
- 观察到蛋白质转化减少,营养感知途径改变 (IGF-1较低,AMPK较高,AKT/TOR/S6K较低),以及代谢/免疫基因表达增强.
- 改善了身体活动,新陈代谢率和脂质代谢.
结论:
- 在小鼠中,MYC活动的部分减少 (haploinsufficiency) 延长了寿命并改善了健康寿命.
- 这种长寿与减少蛋白质合成和改变代谢信号相关,而不是增强抗压能力.
- MYC剂量是影响衰老和哺乳动物健康的关键因素.
相关概念视频
02:23Abnormal Proliferation
5.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.5K
01:06Induced Pluripotent Stem Cells
6.4K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
6.4K
02:15Replicative Cell Senescence
4.7K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.7K
02:15Replicative Cell Senescence
3.5K
3.5K
01:22PI3K/mTOR/AKT Signaling Pathway
6.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
6.5K
03:03mTOR Signaling and Cancer Progression
5.1K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
5.1K