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


Newfound gene could play role in aging from birth

July 17, 2014
Courtesy of the Scripps Research Institute
and World Science staff

It’s some­thing of an eter­nal ques­tion: Can we slow or even re­verse ag­ing? Al­though ge­net­ic ma­nipula­t­ions can al­ter some cel­lu­lar pro­cesses, not so much is known about the mech­a­nisms of the ag­ing pro­cess in liv­ing things.

Now sci­en­tists have found in an­i­mal mod­els that one gene plays a sur­pris­ing role in ag­ing that can be de­tected early on in de­vel­op­ment. They say the dis­cov­ery could point to­ward the pos­si­bil­ity of one day us­ing ther­a­peu­tics, even some com­monly used ones, to ma­ni­pu­late the ag­ing pro­cess it­self.

This “de­vel­op­mental gene, known as Sp­ns1, may me­di­ate the ag­ing pro­cess,” said Shuji Ki­shi, a pro­fes­sor at the from the Flor­i­da cam­pus of The Scripps Re­search In­sti­tute who led the stu­dy, pub­lished by the jour­nal PLoS Ge­net­ics. “Even a par­tial loss of Sp­ns1 func­tion can speed ag­ing.”

Us­ing var­i­ous ge­net­ic ap­proaches to dis­turb Sp­ns1 dur­ing the em­bry­on­ic and/or lar­val stages of ze­brafish—which have emerged as use­ful for stu­dying dis­eases as­so­ci­at­ed with de­vel­op­ment and ag­ing—the sci­en­tists said they pro­duced some mod­els with a short­ened life span, oth­ers that lived long lives.

While most stud­ies of “se­nes­cence”—de­creases in a cel­l’s pow­er of di­vi­sion and growth—have fo­cused on lat­er stages of life, the new study ex­plores early stages. “Muta­t­ions to Sp­ns1 both dis­turbs de­vel­op­mental se­nes­cence and badly af­fects the long-term bio-chronological ag­ing pro­cess,” Ki­shi said.

The study found that Sp­ns1, along with a pair of “tu­mor sup­pres­sor genes,” called be­clin 1 and p53, can in­flu­ence se­nes­cence through two dif­fer­ent mech­a­nisms: the Sp­ns1 de­fect was en­hanced by Be­clin 1 but sup­pressed by ‘basal’ p53. Sp­ns1 also was found to hin­der au­tophagy, a pro­cess where­by cells re­move un­wanted or de­struc­tive pro­teins and bal­ance en­er­gy needs dur­ing var­i­ous life stages.

Build­ing on their in­sights from the stu­dy, Ki­shi and his col­leagues not­ed in the fu­ture ther­a­peu­tics might be able in­flu­ence ag­ing through Sp­ns1. He said a com­monly used ant­ac­id, Prilosec, has been shown to tem­po­rarily sup­press au­tophagic ab­nor­mal­ity and se­nes­cence seen in the Sp­ns1 de­fi­cien­cy.

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It’s something of an eternal question: Can we slow or even reverse aging? Although genetic manipulations can alter some cellular dynamics, not much is known about the mechanisms of the aging process in living things. Now scientists have found in animal models that one gene plays a surprising role in aging that can be detected early on in development. They say the discovery could point toward the possibility of one day using therapeutics, even some commonly used ones, to manipulate the aging process itself. This “developmental gene, known as Spns1, may mediate the aging process,” said Shuji Kishi, a professor at the from the Florida campus of The Scripps Research Institute who led the study, published by the journal PLOS Genetics. “Even a partial loss of Spns1 function can speed aging.” Using various genetic approaches to disturb Spns1 during the embryonic and/or larval stages of zebrafish—which have emerged as useful for studying diseases associated with development and aging—the scientists said they produced some models with a shortened life span, others that lived long lives. While most studies of “senescence”—declines in a cell’s power of division and growth—have focused on later stages of life, the new study explores early stages. “Mutations to Spns1 both disturbs developmental senescence and badly affects the long-term bio-chronological aging process,” Kishi said. The study found that Spns1, along with a pair of “tumor suppressor genes,” called beclin 1 and p53, can influence developmental senescence through two different mechanisms: the Spns1 defect was enhanced by Beclin 1 but suppressed by ‘basal’ p53. In addition to affecting senescence, Spns1 hinders autophagy, the process whereby cells remove unwanted or destructive proteins and balance energy needs during various life stages. Building on their insights from the study, Kishi and his colleagues noted in the future therapeutics might be able influence aging through Spns1. He said a commonly used antacid, Prilosec, has been shown to temporarily suppress autophagic abnormality and senescence observed in the Spns1 deficiency.