Biologists delay the aging process by ‘remote control’
September 8, 2014
University of California – Los Angeles
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.
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
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
“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,
“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
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
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
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
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.
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
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:
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