衰老期间Wnt信号的增加会改变肌肉干细胞的命运,并增加纤维化
Andrew S Brack1, Michael J Conboy, Sudeep Roy
1Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science (New York, N.Y.)
|August 11, 2007
概括
衰老通过促进干细胞纤维化,损害肌肉再生. 老化肌肉干细胞中的Wnt信号激活驱动这种纤维化转化,这表明它.
科学领域:
- 老年学和再生医学的研究.
- 干细胞生物学 干细胞生物学
- 骨肌肉生理学 骨肌肉生理学
背景情况:
- 骨肌肉的再生能力随着年龄的增长而减弱.
- 增加的组织纤维化是与年龄相关的肌肉衰退的标志.
研究的目的:
- 研究与年龄相关的肌肉干细胞功能障碍背后的机制.
- 探索Wnt信号通路在衰老期间肌肉干细胞谱系承诺中的作用.
主要方法:
- 从年轻和老年小鼠获得的肌肉干细胞 (卫星细胞) 的比较分析.
- 在体外评估肌源性与纤维性血统转换的评估.
- 调查标准Wnt信号通路的激活及其通过Wnt抑制剂的调制.
- 来自老老鼠的血清因子的分析及其与Frizzled受体的相互作用.
主要成果:
- 衰老的肌肉干细胞在增殖后表现出从肌源性向纤维性血统转变的倾向.
- 这种血统转换是由老年动物中存在的全身因素介导的.
- 在老年肌原性祖先中观察到正规Wnt信号通路的激活,与纤维化相关.
- Wnt 抑制剂可以抑制这种与年龄相关的血统转换.
- 来自老老小鼠的特定血清成分与Frizzled蛋白质结合,可能导致Wnt信号的升高.
结论:
- Wnt信号通路在组织特异性干细胞的衰老中起着至关重要的作用.
- Wnt信号的失调有助于老化骨肌肉中纤维化增加.
- 准Wnt通路可能提供治疗策略来抵消与年龄相关的肌肉退化.
更多相关视频
06:37Analyzing Satellite Cell Function During Skeletal Muscle Regeneration by Cardiotoxin Injury and Injection of Self-delivering siRNA In Vivo
Published on: September 18, 2019
10:10Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans
Published on: February 16, 2017
相关概念视频
01:19The 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...
02:54Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
01:21Satellite Stem Cells and Muscular Dystrophy
Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...
01:13Formation of Muscle Fibers from Myoblasts
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:26Cellular Adaptation II: Hypertrophy
Hypertrophy is the increase in the size of individual cells, resulting in the enlargement of a tissue or organ. Unlike hyperplasia, which involves an increase in cell number, hypertrophy is characterized by an increase in cell volume. This process often occurs in response to higher functional demand or hormonal stimulation, leading to the production of more structural proteins and organelles, thereby enhancing the cells' work capacity.There are two primary types of hypertrophy: physiological...