"Long before it's in the papers"
April 28, 2009

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Old drug may slow aging, researchers say

Jan. 7, 2009
Courtesy McGill University
and World Science staff

An 80-year old drug once used for in­tes­ti­nal trou­ble can beat back Alz­heim­er’s, Park­in­son’s and Hunt­ing­ton’s dis­eases in an­i­mals, sci­en­tists say.

The re­search­ers the­o­rize that the rea­son for the drug’s far-ranging ef­fects may be that it slows down ag­ing, which is linked to all three dis­or­ders. But the drug was al­so once blamed for an out­break of a nerve dis­or­der, a case in which the facts re­main murky, the sci­en­tists say.

The drug, clio­qui­nol, ap­pears to act on a mol­e­cule in the body called CLK-1, nick­named “clock-1” and linked to the ag­ing pro­cess, ac­cord­ing to the in­ves­ti­ga­tors.

Find­ings from the re­search­ers, at McGill Uni­ver­s­ity in Mont­real, ap­pear in the Oc­to­ber is­sue of the Jour­nal of Bi­o­log­i­cal Chem­is­try.

“Clio­quinol is a very pow­er­ful in­hib­i­tor of clock-1,” said McGill de­vel­op­men­tal bi­olo­g­ist Sieg­fried He­ki­mi. “Be­cause clock-1 af­fects longe­vity in in­ver­te­brates and mice, and be­cause we’re talk­ing about three age-dependent neu­ro­de­gen­er­a­tive dis­eases, we hy­poth­e­size that clio­qui­nol af­fects them by slow­ing down the rate of ag­ing.”

Once com­monly pre­scribed in Eu­rope and Asia for gas­t­ro­in­tes­ti­nal prob­lems like di­ar­rhea and shi­gel­la, clio­qui­nol was with­drawn from the mar­ket af­ter be­ing blamed for a dev­as­tat­ing out­break of sub­a­cute mye­lo-op­tic neu­rop­a­thy in Ja­pan in the 1960s. 

But some re­search­ers think the drug’s cul­pa­bil­ity is un­prov­en, be­cause no rig­or­ous study was con­ducted at the time and the med­ica­t­ion was used safely by mil­lions be­fore and af­ter the event.

Just how clio­quinol in­hibits CLK-1 is still un­der in­ves­ti­ga­t­ion, He­ki­mi said. “One pos­si­bil­ity is that met­als are in­volved, as clio­qui­nol is a met­al che­la­tor,” he ex­plained. Chela­t­ion is a type of bind­ing to met­al atoms and is of­ten used to treat heavy met­al poi­son­ing.

He­ki­mi is op­ti­mis­tic but cau­tious on wheth­er clio­qui­nol could safely and ef­fec­tively fight ag­ing. “The dan­ger is that you can buy a kil­o­gram of this com­pound at a chem­i­cal whole­sal­er, but we don’t want peo­ple to start ex­pe­ri­ment­ing on them­selves. Clio­qui­nol can be a very tox­ic sub­stance if abused, and far more re­search is re­quired.”

A few substances have attracted scientific scru­ti­ny in re­cent years for po­ten­tial anti-aging ef­fects. Many re­search­ers believe one of the most pro­mis­ing is a red wine in­gre­dient called res­ver­a­trol.

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An 80-year old drug once used for intestinal trouble can beat back Alzheimer’s, Parkinson’s and Huntington’s diseases in animals, scientists say. The researchers theorize that the reason for the drug’s far-ranging effects may be that it slows down aging, which is linked to all three disorders. The drug, clioquinol, appears to act on a molecule in the body called CLK-1, nicknamed “clock-1” and linked to the aging process, according to the investigators. But the drug was also once blamed for an outbreak of a nerve disorder, a case in which the facts remain murky, the scientists say. Findings from the researchers, at McGill University in Montreal, appear in the October issue of the Journal of Biological Chemistry. “Clioquinol is a very powerful inhibitor of clock-1,” said McGill developmental biologist Siegfried Hekimi. “Because clock-1 affects longevity in invertebrates and mice, and because we’re talking about three age-dependent neurodegenerative diseases, we hypothesize that clioquinol affects them by slowing down the rate of aging.” Once commonly prescribed in Europe and Asia for gastrointestinal problems like diarrhea and shigella, clioquinol was withdrawn from the market after being blamed for a devastating outbreak of subacute myelo-optic neuropathy in Japan in the 1960s. But some researchers think the drug’s culpability is unproven, because no rigorous study was conducted at the time and the medication was used safely by millions before and after the event. Just how clioquinol inhibits CLK-1 is still under investigation, Hekimi said. “One possibility is that metals are involved, as clioquinol is a metal chelator,” he explained. Chelation is a type of binding to metal atoms and is often used to treat heavy metal poisoning. Hekimi is optimistic but cautious on whether clioquinol could safely and effectively fight aging. “The danger is that you can buy a kilogram of this compound at a chemical wholesaler, but we don’t want people to start experimenting on themselves. Clioquinol can be a very toxic substance if abused, and far more research is required.”