延缓衰老有新法：衰老细胞大清扫

细胞春季大扫除延缓衰老

by Sarah C.P. Williams on 2 November 2011, 2:04 PM

莎拉·威廉姆斯 2011年11月2日,2:04下午

The accumulation of old, stagnant cells in the body is to blame for some age-related diseases, a new study has found. When researchers removed such cells from mice, they were able to delay the onset of cataracts and slow age-related muscle loss.

一项新的研究发现衰老、停滞的细胞在机体积聚是衰老相关疾病发生的原因。 当研究人员设法去除取小鼠体内的这些细胞，小鼠白内障的发病以及老年性肌肉丧失得以延缓。

"This is really a technical tour de force," says geneticist Norman Sharpless of the University of North Carolina School of Medicine in Chapel Hill, who was not involved in the study. "And then they went beyond this technical feat and made findings that are really important to understanding the basic science of aging."

“这的确是一个技术绝技，”Chapel Hill北卡罗莱纳州大学医学院的遗传学家Norman Sharpless说，“他们的研究结果超出了这一技术的壮举，对于了解衰老的基础科学非常重要。” 他没有参与这项研究。 

Most cells in the body can't continue dividing forever. After a cell has duplicated itself a number of times—around 50 is the average—a genetic switch turns off the division program. A cell that's no longer dividing is known as senescent; it continues to live but no longer functions as it once did. While most senescent cells continue to behave as whatever cell type they started as, they also begin to secrete immune proteins that scientists hypothesize could cause age-related changes in the surrounding tissues. In elderly humans, at least 5% of the total cells in the body are thought to be senescent. The cells accumulate in places particularly affected by aging—the eyes and muscles, for example.

机体内大多数细胞不能无限分裂，当一个细胞自我复制超过一定次数(平均50倍左右)，一个基因开关即关闭细胞分裂程序。 一个不再分裂的就是衰老的细胞，它继续存活，但不再像以往一样发挥功能。 虽然大多数衰老细胞仍维持其开始的细胞表型，但它们开始分泌免疫??蛋白，据推测这些蛋白可能导致周围组织的与老化有关的改变。 在老人体内，至少5％的细胞被认为是衰老的，它们积聚在易被老化所影响的部位，如眼睛和肌肉。

"It has been hypothesized, since these cells are found at sites of age-related pathologies, that they are related to the development of these pathologies," says biologist Jan van Deursen of the Mayo Clinic in Rochester, Minnesota, lead author of the new paper. But the connection hasn't been fully fleshed out, he says.

“因为这些细胞在老年相关病理部位被发现，理论上假定它们参与了这些病理发展过程。”在明尼苏达罗彻斯特的梅奥诊所工作的生物学家Jan van Deursen说，他是这篇新论文的第一作者。

Van Deursen and colleagues developed a way to kill senescent cells in mice, clearing them from the body. They engineered mice so that when cells flipped on a gene called p16Ink4a, a marker for senescence, the cell would also turn on the production of inactive cellular death genes, not normally produced by senescent cells. Then, when the researchers gave the mice a drug, the death pathway would be activated in all senescent cells. "Our method allowed us to look at the consequences of removing senescent cells at different stages of the mouse life cycle," van Deursen says. "We didn't just block senescence altogether."

Jan van Deursen和同事开发出一种杀死小鼠的衰老细胞并把它们从体内清除的方法。 他们通过基因工程设计使小鼠细胞含有翻转衰老标志基因P16INK4A，这些细胞也开启非活性死亡基因的表达。 然后，当研究人员给小鼠注射一种药物，衰老细胞的死亡通路会则被激活。 “这一方法可让我们观察小鼠在生命周期的不同阶段去除衰老细胞的后果，”Jan van Deursen说， “我们并不仅仅是完全阻止衰老。”

First, the researchers cleared senescent cells from the mice throughout their lives—giving the drug every 3 days beginning as soon as the animals were weaned. Although the mice did not have an increased life span, the onset of cataracts was delayed by about 100 days, the treated mice had twice as wide muscle fibers, and their spine curvature and fat deposits resembled those of youthful mice. Next, the researchers gave the drug to older mice that already showed signs of aging, such as muscle loss. After 5 months, the treated mice showed better improvement in treadmill tests than untreated mice. Their muscle and fat cells did not show signs of aging, although the treatment didn't reverse aging that had already happened, the team reports online today in Nature.

首先，研究人员从动物断奶开始，每3天给一次药物，清除衰老细胞。 治疗组的小鼠虽然没有增加寿命，但是白内障的发病推迟100天左右，肌纤维粗2倍，脊柱弯曲度和脂肪堆积与年轻小鼠相仿。 然后，研究人员给已经呈现衰老迹象(如肌肉损失)的大龄小鼠治疗。 5个月后，治疗组小鼠比未经处理的小鼠在跑步机测试中表现出较好的改善，虽然治疗并不能扭转已经发生的老化，它们的肌肉和脂肪细胞没有表现出老化的迹象。该课题组的研究结果发表在《自然》杂志。

"I think the results are quite striking," Sharpless says. But he cautions that further research is needed to understand the effects of removing senescent cells. Although they may promote some age-related disorders, they could prevent others. "Whether there are any unintended results of this has to be studied further," he says. "Yes, we might make cataracts better, but will it come with the risk of cancer or infections?"

“我认为这一结果是相当惊人，”夏普勒斯说。 但他警告说，还需要进一步研究，以了解清除衰老细胞的影响。 虽然他们可能对一些与衰老有关的疾病有益，它们也有可能阻止了其他生理过程。 “这有待进一步研究是否有任何其他意外的结果，”他说。 “是的，我们可能会阻止白内障的发展，但是否会增加癌症或感染的风险呢？”

Since the work relied on genetically engineered mice, it's not directly translatable into humans, van Deursen says. Researchers, however, can now screen drugs to find compounds that might activate cell death in senescent cells, he says, or that might turn the immune system against senescent cells.

由于这一工作依靠遗传工程小鼠，它还不能直接转化应用到人类，van Deursen说，然而，研究人员现在可以筛选相关药物，以发现可以激活衰老细胞死亡的化合物，或激活免疫系统杀死衰老细胞。