生物学家通过增加AMPK基因来延缓衰老过程

Biologists Delay the Aging Process by Increasing AMPK Gene

---高强度间歇性运动如举重、俯卧撑、冲刺式奔跑、蹲下，促进一氧化碳合成和释放的营养素/食物如维生素C、大蒜、亚麻籽油，以及阳光中的红外线和紫外线都可以激活AMPK基因。。。。蓝山

图示：
在神经系统中激活一种叫做AMPK的基因，可以在大脑和肠道中诱导自噬的抗衰老细胞循环过程。

激活肠道中的AMPK会增加肠道和大脑的自噬。Matthew Ulgherait, David Walker和加州大学洛

杉矶分校的同事们指出，这种“器官间”的交流方式可以大大延长果蝇的健康寿命。

CREDIT: Matthew Ulgherait /加州大学洛杉矶分校

　

加州大学洛杉矶分校的生物学家通过对果蝇的研究发现，激活果蝇肠道中AMPK的含量增加了约30%的寿命。

 

加州大学洛杉矶分校的生物学家们已经发现了一种基因，这种基因可以在关键器官系统中远程激活，从而减缓整个身体的衰老过程。

 

研究果蝇，生命科学家们激活了一种叫做AMPK的基因，这是细胞中一个关键的能量传感器;当细胞能量水平低时，它就会被激活。

 

增加果蝇肠道内的AMPK含量可以使果蝇的寿命延长30%，从正常的6周延长到大约8周，而且果蝇的寿命也更长。

 

加州大学洛杉矶分校的综合生物学和生理学副教授、该研究的资深作者大卫·沃克说，这项研究在9月4日发表在《细胞报告》(Cell Reports)上，可能对延缓人类衰老和疾病产生重要影响。

 

沃克说:“我们已经证明，当我们激活肠道或神经系统中的基因时，我们可以看到，衰老的过程已经超出了激活基因的器官系统。”

 

沃克说，这一发现很重要，因为延长人类的健康寿命可能需要保护人体的许多器官系统免受衰老的破坏，但向大脑或其他关键器官提供抗衰老的治疗方法在技术上是困难的。研究表明，例如，激活肠道等更容易接近的器官中的AMPK，最终可能会减缓包括大脑在内的整个身体的衰老过程。

 

沃克说，人类有AMPK基因，但它通常不会在高水平上被激活。

 

”与其研究衰老的疾病—帕金森病、阿尔茨海默氏症、癌症、中风、心血管疾病、糖尿病——一个接一个, 我们认为可以干预衰老过程和推迟许多此类疾病的发作,” 沃克说,加州大学洛杉矶分校的分子生物学研究所的成员。“我们还没有达到目标，当然，这可能需要很多年，但这是我们的目标，我们认为这是现实的。”

 

“我们研究的最终目的是促进人们健康的衰老。”

 

　

果蝇，黑腹果蝇是研究人类衰老的一个很好的模型，因为科学家们已经识别出了所有果蝇的基因，并知道如何开关单个基因。生物学家在研究过程中研究了大约10万个果蝇。

 

该研究的第一作者Matthew Ulgherait是沃克实验室的一名博士生，他在实验室中进行了这项研究。研究的重点是一种叫做自噬（AUTOPHAGE）的细胞过程，这种过程可以使细胞降解并丢弃受损的细胞成分。通过清除“细胞垃圾”，在它破坏细胞之前，自噬可以防止衰老，而AMPK已经被证明可以激活这个过程。

 

Ulgherait研究了在果蝇中激活AMPK是否导致自噬发生的频率比通常高。

 

“一个非常有趣的发现是，当马特激活神经系统中的AMPK时，他发现不仅在大脑中，而且在肠道中，自噬水平都有所增加，”加州大学洛杉矶分校学院的教员沃克说。“反之亦然:激活肠道中的AMPK会增加大脑的自噬水平——或许也会增加其他地方的自噬水平。”

 

沃克指出，许多神经退行性疾病，包括阿尔茨海默氏症和帕金森氏症，都与大脑中蛋白质聚集物(一种细胞垃圾)的积累有关。

 

“马特超越了相关性，确立了因果关系，”他说。他表示，自噬的激活对观察其抗衰老作用是必要的，也是充分的; 他可以绕过AMPK，直接瞄准自噬。

　

 

沃克说，AMPK被认为是二甲双胍(一种用于治疗2型糖尿病的药物)的关键目标，二甲双胍激活AMPK。

 

这项研究由美国国立卫生研究院老年研究所资助(授予R01 AG037514和R01 AG040288)。Ulgherait得到了来自美国加州大学洛杉矶分校综合生物学和生理学系的Ruth L. Kirschstein国家研究服务奖(GM07185)和Eureka和Hyde奖学金的资助。

 

这项研究的共同作者是阿尼尔·拉纳，沃克实验室的博士后学者;Michael Rera，前加州大学洛杉矶分校博士后学者，在Walker的实验室;杰奎琳·格拉尼尔，作为加州大学洛杉矶分校的本科生参与了这项研究。

 

在去年发表的一项研究中，沃克和他的同事发现了另一种叫做帕金的基因，这种基因可以延缓果蝇的衰老，延长果蝇的健康寿命。

　

Biologists Delay the Aging Process by Increasing AMPK Gene

 

Working with fruit flies, UCLA biologists showed that increasing the amount of the AMPK gene in fruit flies’ intestines increased their lifespans by about 30 percent.

 

UCLA biologists have identified a gene that can slow the aging process throughout the entire body when activated remotely in key organ systems.

 

Working with fruit flies, the life scientists activated a gene called AMPK that is a key energy sensor in cells; it gets activated when cellular energy levels are low.

 

Increasing the amount of AMPK in fruit flies’ intestines increased their lifespans by about 30 percent — to roughly eight weeks from the typical six — and the flies stayed healthier longer as well.

 

The research, published September 4 in the open-source journal Cell Reports, could have important implications for delaying aging and disease in humans, said David Walker, an associate professor of integrative biology and physiology at UCLA and senior author of the research.

 

“We have shown that when we activate the gene in the intestine or the nervous system, we see the aging process is slowed beyond the organ system in which the gene is activated,” Walker said.

 

Walker said that the findings are important because extending the healthy life of humans would presumably require protecting many of the body’s organ systems from the ravages of aging — but delivering anti-aging treatments to the brain or other key organs could prove technically difficult. The study suggests that activating AMPK in a more accessible organ such as the intestine, for example, could ultimately slow the aging process throughout the entire body, including the brain.

 

Humans have AMPK, but it is usually not activated at a high level, Walker said.

 

“Instead of studying the diseases of aging — Parkinson’s disease, Alzheimer’s disease, cancer, stroke, cardiovascular disease, diabetes — one by one, we believe it may be possible to intervene in the aging process and delay the onset of many of these diseases,” said Walker, a member of UCLA’s Molecular Biology Institute. “We are not there yet, and it could, of course, take many years, but that is our goal and we think it is realistic.

 

“The ultimate aim of our research is to promote healthy aging in people.”

 

The fruit fly, Drosophila melanogaster, is a good model for studying aging in humans because scientists have identified all of the fruit fly’s genes and know how to switch individual genes on and off. The biologists studied approximately 100,000 of them over the course of the study.

 

Lead author Matthew Ulgherait, who conducted the research in Walker’s laboratory as a doctoral student, focused on a cellular process called autophagy, which enables cells to degrade and discard old, damaged cellular components. By getting rid of that “cellular garbage” before it damages cells, autophagy protects against aging, and AMPK has been shown previously to activate this process.

 

Ulgherait studied whether activating AMPK in the flies led to autophagy occurring at a greater rate than usual.

 

“A really interesting finding was when Matt activated AMPK in the nervous system, he saw evidence of increased levels of autophagy in not only the brain, but also in the intestine,” said Walker, a faculty member in the UCLA College. “And vice versa: Activating AMPK in the intestine produced increased levels of autophagy in the brain — and perhaps elsewhere, too.”

 

Many neurodegenerative diseases, including both Alzheimer’s and Parkinson’s, are associated with the accumulation of protein aggregates, a type of cellular garbage, in the brain, Walker noted.

 

“Matt moved beyond correlation and established causality,” he said. “He showed that the activation of autophagy was both necessary to see the anti-aging effects and sufficient; that he could bypass AMPK and directly target autophagy.”

 

Walker said that AMPK is thought to be a key target of metformin, a drug used to treat Type 2 diabetes, and that metformin activates AMPK.

 

The research was funded by the National Institutes of Health’s National Institute on Aging (grants R01 AG037514 and R01 AG040288). Ulgherait received funding support from a Ruth L. Kirschstein National Research Service Award (GM07185) and Eureka and Hyde fellowships from the UCLA department of integrative biology and physiology.

 

Co-authors of the research were Anil Rana, a postdoctoral scholar in Walker’s lab; Michael Rera, a former UCLA postdoctoral scholar in Walker’s lab; and Jacqueline Graniel, who participated in the research as a UCLA undergraduate.

 

In research published last year, Walker and his colleagues identified another gene, called parkin, that delayed the onset of aging and extended the healthy life span of fruit flies.

 

Publication: Matthew Ulgherait, et al., “AMPK Modulates Tissue and Organismal Aging in a Non-Cell-Autonomous Manner,” Cell Reports, 2014; DOI: http://dx.doi.org/10.1016/j.celrep.2014.08.006

 

Source: Stuart Wolpert, UCLA Newsroom

 

Image: Matthew Ulgherait/UCLA

https://scitechdaily.com/biologists-delay-aging-process-increasing-ampk-gene/