[GRG] Increasing AMPK slows aging

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Biologists delay the aging process by ‘remote control’

Date:

September 8, 2014

Source:

University of California – Los Angeles

Summary:

Biologists have identified a gene that can slow the aging process
when activated remotely in key organ systems. The life scientists,
working with fruit flies, activated a gene called AMPK that is a
key energy sensor in cells. Increasing AMPK in the intestine
increased the fly’s life by about 30 percent, and the fly stayed
healthier longer as well. The research could have important
implications for delaying aging and disease in humans.

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Activating a gene called AMPK in the nervous system induces the
anti-aging cellular recycling process of autophagy in both the
brain and intestine. Activating AMPK in the intestine leads to
increased autophagy in both the intestine and brain. Matthew
Ulgherait, David Walker and UCLA colleagues showed that this ‘inter-
organ’ communication during aging can substantially prolong the
healthy lifespan of fruit flies.

Credit: Matthew Ulgherait/UCLA

[Click to enlarge image]

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 Sept. 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.

Story Source:

The above story is based on materials provided by University of
California – Los Angeles. The original article was written by
Stuart Wolpert. Note: Materials may be edited for content and
length.

Journal Reference:
1.Matthew Ulgherait, Anil Rana, Michael Rera, Jacqueline Graniel,
David W. Walker. AMPK Modulates Tissue and Organismal Aging in a
Non-Cell-Autonomous Manner. Cell Reports, 2014; DOI:
10.1016/j.celrep.2014.08.006

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University of California – Los Angeles. “Biologists delay the aging
process by ‘remote control’.” ScienceDaily. ScienceDaily, 8
September 2014.
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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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