減少食物攝取可延長(zhǎng)細(xì)菌和果蠅,、也許還包括人類(lèi)在內(nèi)的多種不同生物的壽命?，F(xiàn)在,，研究發(fā)現(xiàn),，紅酒中所含的一種名叫白藜蘆醇的化合物能延長(zhǎng)果蠅和蠕蟲(chóng)的壽命,。這一發(fā)現(xiàn)使人們想到有可能在不限制營(yíng)養(yǎng)攝取的條件下延長(zhǎng)壽命,。通過(guò)限制營(yíng)養(yǎng)攝取來(lái)延長(zhǎng)壽命實(shí)際上是限制熱量攝取，它與被稱(chēng)為Sirtuins的酶的活性有關(guān),，而白藜蘆醇是一種能激活Sirtuin的化合物,。攝取較少熱量會(huì)導(dǎo)致較長(zhǎng)壽命，但卻有一個(gè)嚴(yán)重的副作用,，如用猴子做的研究表明,，攝取較少熱量會(huì)造成體能減少和不育。飲用紅酒也不是答案，因?yàn)榧t酒中所含白藜蘆醇太少,，在食量過(guò)度所產(chǎn)生的更明顯的副作用表現(xiàn)出來(lái)之前不會(huì)有任何效果,。但施用白藜蘆醇的果蠅仍然保持活躍，仍然有生育能力,，而且想吃多少就吃多少,，卻仍能活得長(zhǎng)一些。因此,，新研制的具有白藜蘆醇一樣性能的化合物也許正好能夠延長(zhǎng)壽命,，而又沒(méi)有人們所不希望的副作用。
Sirtuin activators mimic caloric restriction and delay ageing in metazoans
Caloric restriction extends lifespan in numerous species. In the budding yeast Saccharomyces cerevisiae this effect requires Sir2 (ref. 1), a member of the sirtuin family of NAD+-dependent deacetylases. Sirtuin activating compounds (STACs) can promote the survival of human cells and extend the replicative lifespan of yeast. Here we show that resveratrol and other STACs activate sirtuins from Caenorhabditis elegans and Drosophila melanogaster, and extend the lifespan of these animals without reducing fecundity. Lifespan extension is dependent on functional Sir2, and is not observed when nutrients are restricted. Together these data indicate that STACs slow metazoan ageing by mechanisms that may be related to caloric restriction.
Figure 1 Effect of polyphenolic STACs on sirtuins. a, Sir2 polypeptides from various species. The NAD+-binding pocket (grey), substrate-binding groove (black) and per cent homology to SIRT1 are shown. b, Effect of polyphenolic STACs (500 µM) on TSA-insensitive deacetylase activity in Drosophila S2 cells. c, Fold stimulation of SIR-2.1 by STACs (10 µM). d, Fold stimulation of Drosophila Sir2 by STACs (10 µM). Values are the mean of at least three determinations ( s.e.). e, f, Activation of C. elegans SIR-2.1 (e) and Drosophila Sir2 (f) by resveratrol ( s.e.). g, SIR-2.1 initial rate as a function of NAD+ concentration ( s.e.). AFU, arbitrary fluorescence units.
Figure 2 C. elegans survival on resveratrol. a, Survivorship of adult wild-type N2 C. elegans treated with resveratrol fed with heat-killed OP50 E. coli. b, Survivorship of sir-2.1 mutants treated with resveratrol fed with heat-killed OP50. Adult lifespan of sir-2.1 animals does not differ significantly from N2 controls. c, Survivorship of wild-type N2 C. elegans on 100 µM resveratrol fed with live OP50. d, Survivorship of sir-2.1 mutants on 100 µM resveratrol fed with live OP50. e, Fecundity of adult hermaphrodites on 100 µM resveratrol ( s.d.). f, Feeding rates of L4 larval and adult hermaphrodites treated with 100 µM resveratrol ( s.d.).
Figure 3 Survival of wild-type female D. melanogaster adults fed resveratrol or fisetin. a, Canton-S on 15% SY media. b, Canton-S on 5% SY media. c, yw on 3% CSY media. d, yw on 2% CSY media. e, yw on 3% CSY media. f, yw on 2% CSY media. g, Mean 5 day fecundity per female of Canton-S on 15% SY media resveratrol. h, Proportion of yw females feeding on diet resveratrol in crop-filling assay. i, Mean body mass of Canton-S flies on diet resveratrol (10 µM). Errors represent s.e.
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