Yoon小组研究的蝾螈物种:红斑蝾螈 绿野仙人掌. 通过研究具有非凡再生能力的蝾螈,研究人员发现衰老细胞的存在加速了肢体再生的过程。 这些细胞会分泌一些因子,这些因子会向成熟的肌肉纤维发出信号,使其转化为前肌肉细胞,从而促进再生。 这一发现可以帮助研究人员理解为什么人类的再生能力有限,并可能开发出治疗与年龄有关的疾病的新方法。 图片来源:Maxima Yun


与衰老和疾病相关的衰老细胞可能具有再生特性。 通过研究蝾螈,研究人员发现衰老细胞通过向肌肉纤维发出去分化信号来加速肢体再生,这可能会导致与年龄相关的疾病的新疗法。

衰老细胞是响应细胞应激而永久停止分裂但尚未死亡的细胞。 随着生物体年龄的增长,体内衰老细胞的数量会增加。 这种积聚目前被认为是衰老的标志,并与包括癌症在内的多种疾病有关。 然而,这些细胞的真实性质可能更加复杂并且依赖于上下文。

越来越多的证据表明,衰老细胞也可能具有有益作用,例如愈合伤口或防止组织疤痕形成。 “几年前,我们的小组发现衰老细胞存在于蝾螈肢体再生的关键阶段。有趣的是,其他小组随后在其他再生环境中发现了这些细胞,包括在哺乳动物中。因​​此,我们想看看这些细胞是否有助于它可以以任何方式自我再生,”德累斯顿再生疗法中心 (CRTD) 研究组组长 Maximina Jön 博士解释说,德累斯顿工业大学和马克斯普朗克研究所卓越物理学 (PoL) 组[{” attribute=””>Molecular Cell Biology and Genetics (MPI-CBG).

Senescent Cells Promote Regeneration

The researchers in Yun’s group study salamanders. These animals have unique regeneration abilities and are able to re-grow many organs of their bodies, including lost limbs. “Salamander limb regeneration is a fascinating process. In a matter of weeks, they re-grow a fully functional limb,” explains Dr. Yun.

To check if the presence of senescent cells influences the limb regeneration process, researchers in the Yun group found a way to modulate the number of senescent cells in the wound. The team observed that the presence of senescent cells enhanced the regeneration process.

“When more senescent cells were present in the wound, the animals developed a larger regeneration bud, or – as we call it – blastema. This is a collection of cells that are going to form all the needed tissues in the new limb. The larger the blastema, the more cells are there to regrow the limb and the quicker the regeneration process. The presence of senescent cells seemed to ‘fuel’ the regeneration process,” Dr. Yun says.

“Zombie” Signaling Promotes New Muscle Cells

Looking more closely at the blastema with and without the influence of the senescent cells, the Yun team uncovered a new mechanism that enhances the regeneration process and found that the presence of senescent cells increased the number of regenerating muscle cells. They showed that senescent cells secrete factors that stimulate nearby muscle tissue to take a developmental step back and produce new muscle.

“Our results show that senescent cells use cell-cell communication to influence the regeneration process. They secrete molecules that signal to mature muscle fibers to dedifferentiate into muscle progenitor cells. These cells can multiply themselves as well as differentiate into new muscle cells, thereby enhancing the regeneration process. This signaling appears to be an important part of promoting regeneration,” says Dr. Yun.

For now, the group focused on muscle, one of the most important tissues in the regenerating limb. However, the team is already investigating whether senescent cell signaling also contributes to the regeneration of other tissues.

Lessons From the Salamanders

Yun’s group is working with salamanders to study regeneration and aging processes. “Salamanders are one of the few animal species that seem to defy the natural aging process. They do not develop typical signs of aging and do not accumulate age-related diseases such as cancer. They also have extraordinary healing abilities,” says Dr. Yun. The animals can regenerate almost any organ in their body.

Studying salamanders is helping Dr. Yun and her colleagues at the CRTD understand the principles of the regeneration process and, in the long run, may help solve the puzzle of why humans have very limited regenerative abilities.

Reference: “Senescent cells enhance newt limb regeneration by promoting muscle dedifferentiation” by Hannah E. Walters, Konstantin E. Troyanovskiy, Alwin M. Graf and Maximina H. Yun, 6 April 2023, Aging Cell.
DOI: 10.1111/acel.13826

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