When oxy­gen runs

The Washington Post - - FRONT PAGE - BY BEN GUARINO More at wash­ing­ton­post.com/ news/ speak­ing-of-science

low, naked mole-rats switch their en­ergy source to fruc­tose, the sugar used by plants, a study found.

Naked mole-rats are mar­velous and bizarre ro­dents, ar­guably the world’s weird­est mam­mals. The East African crit­ters do not get tu­mors. They’re im­mune to types of chronic pain and the ir­ri­tant in chili pep­pers. They live like so­cial in­sects, in 300-strong un­der­ground colonies where a mole-rat queen gives birth to worker chil­dren. Though the mole-rats are mam­mals, they do not in­ter­nally reg­u­late their body tem­per­a­tures — they are cold­blooded, so to speak, in the man­ner of frogs. Mice live a max­i­mum of three years. Old Man, the world’s oldest mole-rat, died at 32.

And naked mole-rats thrive in oxy­gen-poor air, even at lev­els that would be lethal to mice or hu­mans. If the naked mole-rats be­have like a strange med­ley of wrin­kled ro­dent, ter­mite and toad, throw veg­etable into that mix, too: When oxy­gen is scarce, as sci­en­tists re­ported Thurs­day in the jour­nal Science, the mole-rats switch their en­ergy source from glu­cose — what hu­mans and vir­tu­ally all other mam­mals use — to fruc­tose. That’s the sugar plants use.

The air you’re breath­ing right now is prob­a­bly about 21 per­cent oxy­gen. The Oc­cu­pa­tional Safety and Health Ad­min­is­tra­tion de­fines “oxy­gen-de­fi­cient” air as less than 19.5 per­cent. Hu­mans, un­less they go through a care­ful ac­cli­ma­tion process, stop func­tion­ing well at around 10 per­cent. Thrust into a cage with air at 5 per­cent oxy­gen, hu­mans would die.

When Thomas Park, an ex­pert on naked mole-rats, placed the first an­i­mal in a cham­ber con­tain­ing 5 per­cent oxy­gen, the mood in the lab, he said, was “tense.” The sci­en­tists be­gan their stop­watches and waited for the slight­est twitch of dis­tress. The an­i­mal, though, seemed un­aware that three­fourths of the oxy­gen in its en­vi­ron­ment had van­ished. Fif­teen min­utes passed. The an­i­mal was un­per­turbed. Min­utes bled into hours. The sci­en­tists called time af­ter 300 min­utes.

“They didn’t even go to sleep,” Park, a Univer­sity of Illi­nois at Chicago neu­ro­bi­ol­o­gist and co-au­thor of the study, told The Wash­ing­ton Post.

The re­searchers tested the an­i­mals at even less oxy­gen: 0 per­cent. The mole-rats fell into a sort of sus­pended an­i­ma­tion while to­tally oxy­gen-de­prived. Their heart rates dropped from 200 beats per minute to about 50. Once the sci­en­tists added oxy­gen back into the mole-rats’ at­mos­phere, the ro­dents made a swift re­cov­ery.

“They were able to sur­vive up to 18 min­utes with­out any ap­par­ent neu­ro­log­i­cal dam­age,” said Jane Reznick, a study co-au­thor and molec­u­lar bi­ol­o­gist at the Max Del­brück Cen­ter for Molec­u­lar Medicine in Ber­lin.

Sci­en­tists knew that naked mole-rats could get by with­out much oxy­gen. Their red blood cells, which trans­port oxy­gen, sport an ul­tra-sticky ver­sion of he­mo­glo­bin that seems to make the cells ex­tra ef­fi­cient. The oxy­gen in the mole-rat’s tun­nels may dip as low as 8 per­cent to 10 per­cent, Park said. No one has been able to probe the air in their crowded sub­ter­ranean nests, where the oxy­gen may dive even lower.

What Park did not ex­pect were the fruc­tose mol­e­cules flood­ing the bod­ies of the oxy­gen-de­prived ro­dents. Us­ing mass spec­trom­e­try, Park and his col­leagues an­a­lyzed tis­sue from the mole-rats’ vi­tal or­gans, in­clud­ing their brains and hearts. The re­searchers tuned the spec­trom­e­ter to search for hundreds of me­tab­o­lites.

“Boy, that was a big pile of data across the desk,” Park said. But the re­searchers did not need to spend a long time sift­ing. “The fruc­tose curves just jumped out.”

Like glu­cose, fruc­tose is a sugar. But or­gan­isms that turn fruc­tose into fuel — plants, and the mol­er­ats — do so with­out re­quir­ing oxy­gen as a key meta­bolic com­po­nent.

Hu­man brains, of course, need oxy­gen to live. “We’ve put all of our chips into the glu­cose path­way,” Park said. Though our cells have the ge­netic in­for­ma­tion re­quired to build the fruc­tose path­way, those are mostly in­ac­tive in vi­tal or­gans such as brains and hearts.

But, be­cause our cells have that in­for­ma­tion, Park has to won­der: “In a time of cri­sis, could we turn our­selves a lit­tle bit into naked mole-rats?”

The idea that sci­en­tists can trans­form naked mole-rat bi­ol­ogy into hu­man ther­apy is still fairly spec­u­la­tive. Park noted that the mole-rat is still lit­tle-stud­ied as an an­i­mal model. Sci­en­tists dis­cov­ered their un­usual pain tol­er­ance in 2009, and re­searchers have had their genome se­quence only since 2011. He hopes this re­search could be a launch­ing point for other sci­en­tists. (An­other in­trigu­ing find­ing: Mole-rat lungs do not fill with fluid when de­prived of oxy­gen, a symp­tom called pul­monary edema, which some high-al­ti­tude moun­tain-climbers ex­pe­ri­ence.)

The mys­ter­ies of the naked mol­er­ats will con­tinue. “We still don’t know where the fruc­tose comes from,” Reznick said. Per­haps the mole-rats have some sort of fruc­tose stor­age sys­tem. If the ro­dents’ bod­ies some­how pro­duced fruc­tose, that would be even stranger. But it’s hard to rule out any od­dity when it comes to naked mole-rats.

COUR­TESY OF JANE REZNICK AND GARY LEWIN

When oxy­gen is scarce, naked mole-rats switch their en­ergy source to fruc­tose, the sugar plants use.

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