"Long before it's in the papers"
April 01, 2015

RETURN TO THE WORLD SCIENCE HOME PAGE


Scientists claim to rescue early-aging mice with new method

April 1, 2015
Courtesy of Centro Nacional de 
Investigaciones Oncologicas
and World Science staff

Bi­ol­o­gists have de­scribed a meth­od by which they say they can dou­ble the life­span of prem­a­turely ag­ing mice.

Wheth­er the find­ings would apply to hu­mans, and even nor­mal ag­ing, is un­clear, but there are some prom­is­ing signs, they add. The re­sults sug­gest that fo­lic ac­id, al­ready pre­scribed for cer­tain symp­toms of ag­ing, may have a role.

In 2009 re­search­ers from the Span­ish Na­t­ional Can­cer Re­search Cen­tre un­der the lead­er­ship of Ós­car Fernández-Capetillo de­scribed how mice with low lev­els a pro­tein called ATR, needed for DNA re­pair, age prem­a­turely. In the new pa­per, pub­lished in the jour­nal Genes & De­vel­op­ment, they de­scribe how they fixed this: in­tro­duc­ing a muta­t­ion that can boost the body’s pro­duc­tion of DNA com­po­nents called nu­cleotides, or dNTPs.

The au­thors built on pre­vi­ous re­search with yeast, which had strains suf­fer­ing from ATR muta­t­ions, like the mice. “Although yeast does not age as such,” the muta­t­ion hurts both or­gan­isms, wrote the re­search­ers.

They cre­at­ed mice that—a­long with the orig­i­nal muta­t­ion caus­ing prem­a­ture ag­ing—al­so had mul­ti­ple cop­ies of Rrm2, the key gene for mak­ing nu­cleotides. The re­sult was the boosted life­span, from an av­er­age of 24 weeks to 50 weeks, the in­ves­ti­ga­tors said. The ATR-mutant mice were based on a hu­man dis­ease called Seckel syn­drome, orig­i­nally known as “bird-headed dwarfis­m.” The newly introduced muta­t­ion not only im­proved the ag­ing but oth­er symp­toms, the re­search­ers said.

Eve­ry liv­ing thing has cer­tain frag­ile ar­eas in its ge­nome. These tend to break, and have been tied to dis­eases in­clud­ing can­cer. The au­thors ar­gue that mice with ex­tra cop­ies of Rrm2 suf­fered less of these breaks.

Wheth­er the re­sults are rel­e­vant to nor­mal, rath­er than prem­a­ture ag­ing re­mains to be seen, the sci­en­tists said. But they note that stand­ard med­i­cal prac­tice in­cludes pre­scrib­ing fo­lic ac­id (or vit­a­min B12) sup­ple­ments to the eld­erly to de­lay or less­en the de­gen­er­a­tive symp­toms as­so­ci­at­ed with ad­vanced age. Fo­lic ac­id is, among oth­er things, a pre­cur­sor mol­e­cule in mak­ing DNA com­po­nents like those pro­duced by Rrm2. 

“The ques­tion we are ask­ing our­selves now” is wheth­er whether a similar change “could al­so length­en life ex­pect­an­cy in nor­mal an­i­mals with­out prem­a­ture age­ing,” said Fernández-Capetillo. Co-author An­drés López-Contreras plans to con­tin­ue the work as head of a lab­o­r­a­to­ry at the Uni­vers­ity of Co­pen­ha­gen.


* * *

Send us a comment on this story, or send it to a friend











aa Sign up for
e-newsletter

   
 
subscribe
 
cancel

On Home Page         

LATEST

  • Glob­al warm­ing doesn’t cause ex­treme win­ters, stu­dy says

  • Lit­tle fish found to kill small­er ones by pos­ing as fam­ily

EXCLUSIVES

  • Study links global warming, war for first time—in Syria

  • Smart­er mice with a “hum­anized” gene?

  • Was black­mail essen­tial for marr­iage to evolve?

  • Plu­to has even cold­er “twin” of sim­ilar size, studies find

MORE NEWS

  • F­rog said to de­scribe its home through song

  • Even r­ats will lend a help­ing paw: study

  • D­rug may undo aging-assoc­iated brain changes in ani­mals

Biologists have described a method by which they say they can double the lifespan of prematurely aging mice. Whether the findings would apply to humans, and even normal aging, is unclear, but there are some promising signs, they add. The results suggest that folic acid, already prescribed for certain symptoms of aging, may have a role. In 2009 researchers from the Spanish National Cancer Research Centre under the leadership of Óscar Fernández-Capetillo described how mice with low levels a protein called ATR, needed for DNA repair, age prematurely. In the new paper, published in the journal Genes & Development, the group describes how they fixed this: introducing a mutation that could boost the body’s production of DNA components called nucleotides, or dNTPs. The authors built on previous research with the yeast Saccharomyces cerevisiae, which had strains suffering from ATR mutations, like the mice. “Although yeast does not age as such,” the mutation hurts both organisms, wrote the researchers. They created mice that—along with the original mutation causing premature ageing—also had multiple copies of Rrm2, the key gene for making nucleotides. The result was the boosted lifespan, from an average of 24 weeks to 50 weeks, the investigators said. The ATR-mutant mice were based on a human disease called Seckel syndrome, originally known as “bird-headed dwarfism.” The second-introduced mutation not only improved the aging but also other symptoms, the researchers said. Every living thing has certain fragile areas in its genome. These tend to break, and have been tied to diseases including cancer. The authors argue that mice with extra copies of Rrm2 suffered less of these breaks. Whether the results are relevant to normal, rather than premature aging remains to be seen, the scientists said. But they note that standard medical practice includes prescribing folic acid (or vitamin B12) supplements to the elderly to delay or lessen the degenerative symptoms associated with advanced age. Folic acid is, among other things, a precursor molecule in making DNA components like those produced by Rrm2. “The question we are asking ourselves now is whether an increase in the capacity to produce nucleotides could also lengthen life expectancy in normal animals without premature ageing,” said Fernández-Capetillo. Co-author Andrés López-Contreras plans to continue the work as head of a laboratory at the University of Copenhagen.