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“Longevity gene” may be unrelated to longevity

Sept. 21, 2011
Courtesy of the Wellcome Trust
and World Science staff

Pro teins thought to boost life span in sev er al test or gan isms—and said to be stim u lat ed by cer tain “anti-aging” prod uct s—don’t really af fect longe vity, new re search sug gests.

That does n’t mean life span can not be ex tend ed, sci en tists said; it just means any tech niques that have suc ceeded in do ing so were probably not work ing through those pro teins.



The round worm C. ele gans, used in some ag ing studies. (Im age cour tesy free.ed.gov)

Pre vi ous stud ies had linked the nat u ral molecules, known as sir tu ins, to age ing and longe vity in or gan isms in clud ing yeast, nem a tode worms and fruit flies, of ten used as mod els for the bi ol o gy of hu man age ing. Re search ers had shown that when the or gan is ms over pro duced sir tuin, they lived long er, by as much as 50 per cent in the case of nem a todes.

Oth er re search iden ti fied a link be tween sir tu ins and di e tary re stric tion – a sharp cut back in calo ries eat en, a meth od known to ex tend life span in many or gan isms, in clud ing some mam mals. Re search sug gested that it works by ac ti vat ing the pro duc tion of sir tu ins. The stud ies caused much in ter est among sci en tists and oth ers. Some dubbed the sir tuin-producing gene the “longe vity gene.”

Pills and “anti-age ing” creams have al so been launched con tain ing res ver a trol, a sub stance found in red wine and thought to ac ti vate sir tu ins.

But sub se quent re search has cast doubt on the claims that res ver a trol ac ti vates sir tu ins. A study pub lished Sept. 21 in the jour nal Na ture, led by Da vid Gems and col leagues at Uni vers ity Col lege Lon don, pro vides al most con clu sive ev i dence that the ef fects on an i mal longe vity seen in ear li er ex pe ri ments were un con nect ed to sir tuin, the in ves ti ga tors said.

“These re sults are very sur pris ing. We have re-ex am ined the key ex pe ri ments link ing sir tuin with longe vity in an i mals and none seem to stand up to close scru ti ny. Sir tu ins, far from be ing a key to longe vity, ap pear to have noth ing to do with ex tending life,” Gems said. “But I think this is good news in a way: af ter all, re vis ing old ideas can be as im por tant as pre sent ing new ones to as sure sci en tif ic prog ress. This work should help to re di rect sci en tif ic ef forts to ward those pro cesses that really do con trol age ing.”

Gems and col leagues, with re search ers at the Uni vers ity of Wash ing ton, Se at tle, and Sem mel weis Uni vers ity, Bu da pest, ex am ined two strains of nem a tode worm, each from a dif fer ent pri or stu dy. These were ma ni pu lated to have a hy per ac tive sir tuin gene. They did live long er than nor mal worms, but af ter pre cau tions were tak en to en sure that the only dif fer ence be tween the nor mal and test worms was high er sir tuin lev els, the longe vity ef fect was found to van ish.

Thus some thing else must have caused the longe vity, the sci en tists pro pose. In one of the two orig i nal strains, they iden ti fied this as a muta t ion in a gene in volved in nerve cell de vel op ment.

Work ing with col leagues at the Uni vers ity of Mich i gan, the U.K. re search ers then ex am ined an en gi neered ver sion of the fruit fly, Dro soph i la melanogaster, in which sir tuin lev els were al so raised. The same or gan ism had been the sub ject of ear li er re search which seemed to show that over ac tiva t ion of sir tu ins in creased longe vity.

Gems and col leagues pro pose ge net ic fac tors oth er than sir tu ins genes were the cause of the longe vity. They al so cre at ed a new strain of fruit fly with even high er sir tuin lev els, but found that this was n’t long-lived ei ther.

The re search ers al so pre pared syn thet ic fruitfly sir tuin and tested wheth er it could be ac ti vated by res ver a trol, as pre dicted by pre vi ous claims. But nei ther the U.K. or U.S. lab o r a to ries, each us ing sev er al tech niques, could show any ac tiva t ion. Fi nal ly, the teams re-tested the claim that di e tary re stric tion in creases life span by ac ti vat ing sir tu ins. Tak ing mu tant fruit flies that lacked the sir tuin gene, the re search ers showed that di e tary re stric tion still in creased life span. So di e tary re stric tion was work ing in de pend ently of sir tu ins, they said.