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Jake Jacobson Adrian J. Lambert Manuel Portero‐Otín Reinald Pamplona Tapiwanashe Magwere Satomi Miwa Yasmine Driege Martin D. Brand Linda Partridge 《Aging cell》2010,9(4):466-477
Low environmental temperature and dietary restriction (DR) extend lifespan in diverse organisms. In the fruit fly Drosophila, switching flies between temperatures alters the rate at which mortality subsequently increases with age but does not reverse mortality rate. In contrast, DR acts acutely to lower mortality risk; flies switched between control feeding and DR show a rapid reversal of mortality rate. Dietary restriction thus does not slow accumulation of aging‐related damage. Molecular species that track the effects of temperatures on mortality but are unaltered with switches in diet are therefore potential biomarkers of aging‐related damage. However, molecular species that switch upon instigation or withdrawal of DR are thus potential biomarkers of mechanisms underlying risk of mortality, but not of aging‐related damage. Using this approach, we assessed several commonly used biomarkers of aging‐related damage. Accumulation of fluorescent advanced glycation end products (AGEs) correlated strongly with mortality rate of flies at different temperatures but was independent of diet. Hence, fluorescent AGEs are biomarkers of aging‐related damage in flies. In contrast, five oxidized and glycated protein adducts accumulated with age, but were reversible with both temperature and diet, and are therefore not markers either of acute risk of dying or of aging‐related damage. Our approach provides a powerful method for identification of biomarkers of aging. 相似文献
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Modulation of caveolae by insulin/IGF‐1 signaling regulates aging of Caenorhabditis elegans
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Hana Boocholez Lorna Moll Filipa Carvalhal Marques Ludmila Golodetzki Yuval Nevo Tayir Elami Ehud Cohen 《EMBO reports》2018,19(8)
Reducing insulin/IGF‐1 signaling (IIS) extends lifespan, promotes protein homeostasis (proteostasis), and elevates stress resistance of worms, flies, and mammals. How these functions are orchestrated across the organism is only partially understood. Here, we report that in the nematode Caenorhabditis elegans, the IIS positively regulates the expression of caveolin‐1 (cav‐1), a gene which is primarily expressed in neurons of the adult worm and underlies the formation of caveolae, a subtype of lipid microdomains that serve as platforms for signaling complexes. Accordingly, IIS reduction lowers cav‐1 expression and lessens the quantity of neuronal caveolae. Reduced cav‐1 expression extends lifespan and mitigates toxic protein aggregation by modulating the expression of aging‐regulating and signaling‐promoting genes. Our findings define caveolae as aging‐governing signaling centers and underscore the potential for cav‐1 as a novel therapeutic target for the promotion of healthy aging. 相似文献
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