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September 9, 2014

Activated Gene Slows the Aging Process

  • Scientists at UCLA say they 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 researchers activated the AMPK gene 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% (to roughly eight weeks from the typical six) and the flies stayed healthier longer as well.

    The study (“AMPK Modulates Tissue and Organismal Aging in a Non-Cell-Autonomous Manner”), published in Cell Reports, could have important implications for delaying aging and disease in humans, said David Walker, Ph.D., 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," noted Walker, who added 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. However, 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, 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 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.

    “Upregulation of AMPK in the adult intestine induces autophagy both cell autonomously and non-cell-autonomously in the brain, slows systemic aging, and prolongs the lifespan,” wrote the investigators. “We show that the organism-wide response to tissue-specific AMPK/Atg1 activation is linked to reduced insulin-like peptide levels in the brain and a systemic increase in 4E-BP expression. Together, these results reveal that localized activation of AMPK and/or Atg1 in key tissues can slow aging in a non-cell-autonomous manner.”

    According to Dr. Walker 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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