持续时间独立的胰岛素/IGF-1信号意味着长寿的原重塑
Collin Y Ewald1, Jess N Landis2, Jess Porter Abate1
11] Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA [2] Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA [3] Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02215, USA.
Nature
|December 18, 2014
概括
降低胰岛素/IGF-1信号传导 (rIIS) 通过独立于 dauer 的途径延长了 C. elegans 的寿命,利用 SKN-1 促进原蛋白的产生并保持细胞外基质的年轻度以延长寿命.
科学领域:
- 老年学是指老年学的学科.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 衰老包括细胞损伤和细胞外基质 (ECM) 衰退.
- 降低胰岛素/IGF-1信号传导 (rIIS) 可以延长寿命,但其ECM影响尚不清楚.
- 劳动路径与rIIS寿命延长有关,但存在其他替代机制.
研究的目的:
- 研究RIIS如何在衰老过程中影响ECM.
- 为了确定独立于时间的衰老路径.
- 探索SKN-1在rIIS中介寿命和ECM维护中的作用.
主要方法:
- 使用Caenorhabditis elegans作为一个模型生物.
- 使用基因操纵来研究RIIS,DAF-16和SKN-1通路.
- 分析了基因表达,专注于原体和ECM组件.
- 在各种遗传和环境条件下评估寿命.
主要成果:
- rIIS通过与SKN-1有关的独立路径促进C. elegans的长寿.
- 当SKN-1被低IIS没有Dauer特征激活时,会对原和ECM基因表达进行上调.
- 不同的长寿干预措施延迟了与年龄相关的原蛋白表达的下降.
- 通过原介导的ECM重塑对于在时间独立的rIIS路径中延长寿命至关重要.
结论:
- IIS调节成年C. elegans的各种保护机制.
- 一个涉及SKN-1和ECM重塑的Dauer独立路径有助于长寿.
- 保持ECM年轻度对于各种抗衰老干预措施的有效性至关重要.
相关概念视频
Insulin: The Receptor and Signaling Pathways
6.4K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
6.4K
Type IV Collagen of Basal Lamina
3.5K
Type IV collagen is a 400 nm long, network-forming collagen that acts as a barrier between the epithelial and endothelial cells. Type IV collagen forms the backbone of the basement membrane by scaffolding with laminin, entactin, proteoglycans, and fibronectin. Apart from rendering structural support to the basement membrane, it also helps entail signaling potentials necessary for both pathological and physiological functions.
A type IV collagen molecule has six alpha chains which can...
A type IV collagen molecule has six alpha chains which can...
3.5K
The Effect of Aging on Tissues
4.2K
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...
4.2K
Structural Protein Function
30.6K
Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
30.6K
Insulin: Dosing Regimen and Adverse Effects
1.3K
Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
1.3K
TGF - β Signaling Pathway
11.1K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
11.1K


