降低的NAD (((+) 诱导了伪阴极状态,在衰老过程中破坏了核线粒体通信
Ana P Gomes1, Nathan L Price2, Alvin J Y Ling2
1Glenn Labs for the Biological Mechanisms of Aging, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Center for Neurosciences and Cell Biology, 3004-517 Coimbra, Portugal; Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, 3004-517 Coimbra, Portugal.
Cell
|December 24, 2013
概括
衰老导致线粒体氧化酸化 (OXPHOS) 子单元的特定损失,这是由于核-线粒体通信受损. 恢复NAD ((+) 水平可以逆转这种与年龄相关的线粒体功能障碍.
科学领域:
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
- 线粒体生物学 线粒体生物学
背景情况:
- 细胞需要核和线粒体基因组之间的协调,以进行氧化酸化 (OXPHOS).
- 线粒体功能障碍是衰老的关键特征,但其潜在机制仍然不清楚.
- 核和线粒体基因表达之间的相互作用对于细胞能量生产至关重要.
研究的目的:
- 调查老化期间线粒体功能障碍的特定分子原因.
- 为了确定核和线粒体基因组之间受衰老影响的通信途径.
- 探索潜在的干预措施,以逆转与年龄相关的线粒体衰退.
主要方法:
- 在老年小鼠中分析线粒体和核编码的OXPHOS子单元.
- 研究涉及NAD (+) 和HIF-1α的PGC-1α/β独立通路.
- 在老年小鼠中进行基因操纵 (SIRT1删除) 和药理干预 (NAD(+) 恢复水平).
主要成果:
- 衰老导致线粒体编码的OXPHOS子单元的选择性损失,而不是核编码的.
- 核NAD的下降 (((+) 和HIF-1α在normxia下的积累引发了伪缺氧状态,破坏了核-线粒体通信.
- 在老老鼠中以SIRT1依赖的方式恢复NAD (+) 水平,使线粒体功能复苏.
结论:
- 由降低的NAD ((+)) 和增加的HIF-1α驱动的伪缺氧状态,损害了核-线粒体通信,并导致与年龄相关的线粒体功能障碍.
- 这种与年龄相关的线粒体功能的下降可以通过恢复NAD(+) 水平的干预来逆转.
- 这些发现突出了对抗衰老和相关线粒体疾病的新疗法目标.
相关概念视频
01:37Mitochondria
13.4K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
13.4K
01:26Aging
1.1K
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...
1.1K
01:46Electron Transport Chain: Complex I and II
11.9K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
11.9K
01:45Mitochondrial Membranes
11.7K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
11.7K
01:19The Effect of Aging on Tissues
3.6K
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...
3.6K
01:16Necrosis
5.2K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
5.2K