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UCLA Biologists Identify Gene that Can Be Activated to Delay Aging

UCLA Biologists Identify Gene that Can Be Activated to Delay Aging

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

Scientists activated a gene in fruit flies’ intestines called AMPK that is a key sensor that normally is only activated when energy levels are very low in cells. Increasing the amount of AMPK in fruit flies’ intestines increased their lifespans by about 30%, and the flies stayed healthier during their lives. Since activating AMPK is already used in treating Type 2 diabetes, there is a good probability this “fountain of youth” treatment will be approved for use in humans in the next few years.

The research, published in the journal Cell Reports on September 4th, could have important implications for delaying aging and disease in humans, said Senior author David Walker, Associate Professor of Integrative Biology and Physiology at UCLA: “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 that extending the healthy life of humans would 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 is technically difficult. His study suggests that activating AMPK in an accessible organ such as the intestine could ultimately slow the aging process throughout the entire body, including the brain.

The anti-aging cellular recycling process called autophagy takes place in organs in the human body. When AMPK is activated in the intestine, it leads to increased autophagy in both the intestine and brain. This “inter-organ” communication has the potential to substantially prolong the healthy lifespan of human beings.

The AMPK is usually not activated at high levels in humans, according to 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 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,” he added.

The fruit fly, Drosophila melanogaster, has been used for decades as a good model for studying humans because scientists have identified all of the fruit fly’s genes and know how to switch individual genes on and off. The UCLA biologists studied approximately 100,000 of them over the course of their anti-aging study.

The study focused on the cellular process of autophagy, which enables cells to degrade and discard old, damaged cellular components. Lead author Mathew Ulgherait said that autophagy getting rid of that “cellular garbage” before it can damage other cells protects life against aging. So Ulgherait focused on whether activating AMPK in the fruit flies could lead 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.”

Neurodegenerative diseases, including both Alzheimer’s and Parkinson’s, are often associated with the accumulation of protein aggregates, a type of cellular garbage, in the brain. “Matt moved beyond correlation and established causality,” Walker 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 added that AMPK activation was already thought to be a key target of the drug metformin, known by its brand names of Fortamet and Glucophage, used to treat Type 2 diabetes.

The fact that AMPK activation studies have already been extensively reviewed by the FDA may shorten the length of time before clinical studies in humans can begin for what may legitimately be the fountain of youth.

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