‘ Zom­bie cells’ refuse to die, pro­mote ag­ing con­di­tions

Drugs to kill, cure sought by re­searchers

The Republican Herald - - FRONT PAGE - BY MAL­COLM RIT­TER

NEW YORK — Call them zom­bie cells — they refuse to die.

As they build up in your body, stud­ies sug­gest, they pro­mote ag­ing and the con­di­tions that come with it like os­teo­poro­sis and Alzheimer’ s dis­ease. Re­searchers are study­ing drugs that can kill zom­bie cells and pos­si­bly treat the prob­lems they bring.

Ba­si­cally the goal is to fight ag­ing it­self, which hope­fully will in turn de­lay the ap­pear­ance of age- re­lated dis­ease and dis­abil­i­ties as a group, said geri­atrics spe­cial­ist Dr. James Kirk­land of the Mayo Clinic in Rochester, Min­nesota. That’s in con­trast to play­ing a “whack- a- mole game” of treat­ing one dis­ease only to see an­other spring up, he said.

The re­search has been done chiefly in mice. Ear­lier this year, the first test in peo­ple was pub­lished and pro­vided some tan­ta­liz­ing re­sults.

Zom­bie cells are ac­tu­ally called senes­cent cells. They start out nor­mal but then en­counter a stress, like dam­age to their DNA or vi­ral in­fec­tion. At that point, a cell can choose to die or be­come a zom­bie, ba­si­cally en­ter­ing a state of sus­pended an­i­ma­tion.

The prob­lem is that zom­bie cells re­lease chem­i­cals that can harm nearby nor­mal cells. That’s where the trou­ble starts.

What kind of trou­ble? In mouse stud­ies, drugs that elim­i­nate zom­bie cells — so- called senolyt­ics — have been shown to im­prove an im­pres­sive list of con­di­tions, such as cataracts, di­a­betes, os­teo­poro­sis, Alzheimer’s dis­ease, en­large­ment of the heart, kid­ney prob­lems, clogged ar­ter­ies and age- re­lated loss of mus­cle.

Mouse stud­ies have also shown a more di­rect tie be­tween zom­bie cells and ag­ing. When drugs tar­get­ing those cells were given to aged mice, the an­i­mals showed bet­ter walk­ing speed, grip strength and en­durance on a tread­mill. Even when the treat­ment was ap­plied to very old mice, the equiv­a­lent of peo­ple ages 75 to 90, it ex­tended life­span by an av­er­age of 36 per­cent.

Re­searchers have also shown that trans­plant­ing zom­bie cells into young mice ba­si­cally made them act older: their max­i­mum

walk­ing speed slowed down, and their mus­cle strength and en­durance de­creased. Tests showed the im­planted cells con­verted other cells to zom­bie sta­tus.

Kirk­land and col­leagues this year pub­lished the first study of a zom­bie- cell treat­ment in peo­ple. It in­volved 14 pa­tients with id­io­pathic pul­monary fi­bro­sis, a generally fa­tal dis­ease that scars the lin­ing of the lungs. Risk rises with age, and the lungs of pa­tients show ev­i­dence of zom­bie cells.

In the pre­lim­i­nary ex­per­i­ment, af­ter three weeks of treat­ment, pa­tients im­proved on some mea­sures of phys­i­cal fit­ness, like walk­ing speed. Other mea­sures did not show im­prove­ment.

Over­all, the re­sults are en­cour­ag­ing and “it re­ally raises en­thu­si­asm to pro­ceed with the more rig­or­ous stud­ies,” said Dr. Gre­gory Cos­grove, chief med­i­cal of­fi­cer of the Pul­monary Fi­bro­sis Foun­da­tion, who played no role in the study.

The field of zom­bie cells is still young. But Kirk­land es­ti­mates at least a dozen com­pa­nies have formed or have launched ef­forts to pur­sue treat­ments. He holds shares in one.

Apart from age- re­lated dis­eases, anti- zom­bie drugs might be use­ful for treat­ing pre­ma­ture ag­ing among can­cer sur­vivors that brings on the early ap­pear­ance of some dis­eases, said Laura Niedern­hofer of the Univer­sity of Min­nesota.

Some of these drugs have been ap­proved for other uses or are even sold as sup­ple­ments. But Niedern­hofer and Kirk­land stress that peo­ple should not try them on their own, nor should doc­tors pre­scribe them, for the uses now un­der study be­cause more re­search has to be done first.

UNIvER­SITy OF MIN­NESOTA vIA AP

“Zom­bie” cells start out nor­mal but then en­counter a stress, like dam­age to their DNA or vi­ral in­fec­tion. At that point, a cell can choose to die or be­come a zom­bie, which means they stop go­ing through their nor­mal cy­cle of ac­tiv­i­ties. The prob­lem is that they then start se­cret­ing sub­stances that can harm nearby nor­mal cells.

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