Activating Gene Slows the Aging Process by “Remote Control”

The life scientists, working with fruit flies, switched on a gene called AMPK (AMP-activated protein kinase), which is a major energy sensor in cells.

Increasing AMPK in the intestine increased the fly’s life by approximately 30%, and the fly stayed healthier longer as well. The new research could have significant implications for delaying human aging and disease. Activating AMPK in the central nervous system (CNS) was shown to induce the antiaging cellular recycling process of autophagy in both the brain and intestine. The researchers showed that this ‘interorgan’ communication during aging can substantially prolong the healthy lifespan of fruit flies.

The research, published September 4, 2014, in the open-source journal Cell Reports, could have important implications for delaying aging and disease in humans, according to Dr. David Walker, an associate professor of integrative biology and physiology at the University of California, Los Angeles (UCLA; USA), 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,” he said.

Dr. Walker stated 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 instance, 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, according to Dr. Walker. “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 Dr. 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 researching human aging 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 Dr. Matthew Ulgherait, who conducted the research in Dr. 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.

Dr. 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 Dr. 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 linked with the accumulation of protein aggregates, a type of cellular garbage, in the brain, Dr. Walker noted. “Matt moved beyond correlation and established causality,” he said. “He showed that the activation of autophagy was both necessary to see the antiaging effects and sufficient; that he could bypass AMPK and directly target autophagy.”

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

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