"Long before it's in the papers"
January 27, 2015


Study suggests delaying aging may be easier than thought

Sept. 9, 2014
Special to World Science  

A study has linked a type 2 di­a­be­tes drug to small in­creases in peo­ple’s life­spans. And a sep­a­rate study has found great­er life­span boosts in fruit flies, from a treat­ment thought to work in a si­m­i­lar way.

Both are believed to boost the ac­ti­vity of a gene called AMPK, which in turn fa­cil­i­tates what bi­ol­o­gists de­scribe as a ti­ny “gar­bage dis­pos­al” pro­cess with­in cells of the body.

The study of 180,000 peo­ple in the U.K. found that the di­a­be­tes drug, met­formin, was as­so­ci­at­ed with a “small but sig­nif­i­cant im­prove­ment in sur­vival” in those who were pre­scribed the drug, com­pared to non-diabetic pa­tients, said Craig Cur­rie from Car­diff Uni­vers­ity’s School of Med­i­cine in the U.K. The work, by Cur­rie and col­leagues, is re­ported in the Oc­to­ber is­sue of the jour­nal Obes­ity, Di­a­be­tes and Me­tab­o­lism. More re­search is planned.

Sep­a­rate­ly, the fruit fly study sug­gested that a treat­ment which af­fects AMPK might slow the whole bod­y’s ag­ing pro­cess when ac­tivated in only a few key or­gans. The re­search­ers in the proj­ect said this sug­gests an­ti-ag­ing treat­ments could be eas­i­er to de­vel­op than had been thought, as such treat­ments could there­by avoid the dif­fi­cult feat of hav­ing to tar­get eve­ry or­gan.

The fruit fly re­search­ers ac­tivated AMPK in the in­sects. The gene is a key “en­ergy sen­sor” in cells: it be­comes ac­tive when cells run low on en­er­gy. Boost­ing its ac­ti­vity in fruit flies’ in­testines in­creased their life­spans by about 30 per­cent and the flies stayed health­i­er long­er as well, ac­cord­ing to the re­search­ers.

Al­though an an­i­mal’s ge­net­ic code is more or less fixed, dif­fer­ent genes can be more or less ac­tive at dif­fer­ent times. Bi­ol­o­gists be­lieve that boost­ing the ac­ti­vity of AMPK has ef­fects on life­span be­cause the gene fa­cil­i­tates a sys­tem of so-called gar­bage dis­pos­al that oc­curs with­in cells, and which is al­so thought to help slow the ag­ing pro­cess. 

In fruit flies, “when we ac­tivate the gene in the in­tes­tine or the nerv­ous sys­tem, we see the ag­ing pro­cess is slowed be­yond the or­gan sys­tem” tar­geted, said Da­vid Walk­er, a bi­ol­o­gist at the Uni­vers­ity of Cal­i­for­nia Los An­ge­les. He is sen­ior au­thor of the re­search, pub­lished Sept. 4 in the re­search jour­nal Cell Re­ports.

Walk­er and col­leagues worked with fruit flies ge­net­ic­ally en­gi­neered to make it easy to “switch” spe­cif­ic genes on and off.

Walk­er said the fruit fly find­ings are im­por­tant be­cause ex­tend­ing healthy life in hu­mans would pre­sumably re­quire pro­tect­ing many or­gan sys­tems from the rav­ages of ag­ing. Yet de­liv­er­ing an­ti-ag­ing treat­ments to the brain or oth­er key or­gans could prove dif­fi­cult. The study sug­gests that ac­tivating AMPK in an or­gan such as the in­tes­tine, which is rel­a­tively ac­ces­si­ble to drugs, could be enough.

Hu­mans have AMPK, but it’s sel­dom very ac­tive nat­u­ral­ly, Walk­er said. Lead au­thor Mat­thew Ul­gherait, who con­ducted the re­search in Walk­er’s lab­o­r­a­to­ry as a doc­tor­al stu­dent, fo­cused on a cel­lu­lar pro­cess called au­tophagy, which lets cells de­grade and dis­card old, dam­aged cel­lu­lar com­po­nents. By get­ting rid of that “cel­lu­lar gar­bage” be­fore it dam­ag­es cells, au­tophagy is thought to pro­tect against ag­ing. AMPK was shown pre­vi­ously to ac­tivate this pro­cess.

“When Matt ac­tivated AMPK in the [fruit fly] nerv­ous sys­tem, he saw ev­i­dence of in­creased lev­els of au­tophagy in not only the brain, but al­so in the in­tes­tine,” said Walk­er. “And vi­ce versa: Ac­ti­vat­ing AMPK in the in­tes­tine pro­duced in­creased lev­els of au­tophagy in the brain—and per­haps else­where.”

Ul­gherait al­so “estab­lished caus­al­ity,” Walk­er said, show­ing that ac­tivating au­tophagy was both nec­es­sary and suf­fi­cient. “He could by­pass AMPK and di­rectly tar­get au­tophagy.” Walk­er not­ed that met­formin is thought to ac­tivate the gene.

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A study has linked a type 2 diabetes drug to small increases in people’s lifespans. And a separate study has found greater lifespan boosts in fruit flies, from a treatment thought to work in a similar way. Both treatments are thought to increase the activity of a gene called AMPK, which in turn facilitates what biologists describe as a tiny “garbage disposal” process within cells of the body. The study of 180,000 people in the U.K. found that the diabetes drug, metformin, was associated with a “small but significant improvement in survival” in those who were prescribed the drug, compared to non-diabetic patients, said Craig Currie from Cardiff University’s School of Medicine in the U.K. The work appears in the October issue of the journal Obesity, Diabetes and Metabolism. Separately, the fruit fly study suggested that a treatment which affects AMPK might slow the whole body’s aging process when activated in only a few key organs. The researchers in the project said this suggests anti-aging treatments could be easier to develop than had been thought, as such treatments could thereby avoid the difficult feat of having to target every organ. The fruit fly researchers activated AMPK in the insects. The gene is a key “energy sensor” in cells: it becomes active when cells run low on energy. Boosting its activity in fruit flies’ intestines increased their lifespans by about 30 percent and the flies stayed healthier longer as well, according to the researchers. Although an animal’s genetic code is more or less fixed, different genes can be more or less active at different times. Biologists believe that boosting the activity of AMPK has effects on lifespan because the gene facilitates a system of so-called garbage disposal that occurs within cells, and which is also thought to help slow the aging process. In fruit flies, “when we activate the gene in the intestine or the nervous system, we see the aging process is slowed beyond the organ system” targeted, said David Walker, a biologist at the University of California Los Angeles. He is senior author of the research, published Sept. 4 in the research journal Cell Reports. Walker and colleagues worked with fruit flies genetically engineered to make it easy to “switch” specific genes on and off. Walker said the fruit fly findings are important because extending healthy life in humans would presumably require protecting many organ systems from the ravages of aging. Yet delivering anti-aging treatments to the brain or other key organs could prove difficult. The study suggests that activating AMPK in an organ such as the intestine, which is relatively accessible to drugs, could be enough. Humans have AMPK, but it’s seldom very active naturally, Walker said. Lead author Matthew Ulgherait, who conducted the research in Walker’s laboratory as a doctoral student, focused on a cellular process called autophagy, which lets cells degrade and discard old, damaged cellular components. By getting rid of that “cellular garbage” before it damages cells, autophagy is thought to protect against aging. AMPK was shown previously to activate this process. “When Matt activated AMPK in the [fruit fly] 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.” Ulgherait also “established causality,” Walker said, showing that activating autophagy was both necessary and sufficient. “He could bypass AMPK and directly target autophagy.” Walker noted that metformin is thought to activate the gene.