SIRT1, TOR und das Altern von Wirbelsäulen: Versuche mit klein-Molekülen
Final Report Abstract
In the present project, we tested the effects of dietary restriction, resveratrol and rapamycin in two different strains of the short-lived fish Nothobranchius furzeri. In particular, we used the strain "GRZ" that is highly inbred and has a median lifespan of ~3 months and the strain MZM0410 that is more outbred and has a median lifespan on ~8 months. The results were as following: -Dietary restriction pronged lifespan in the GRZ strain, but had a mixed effects in the MZM0410 strain by increasing early mortality but decreasing late mortality. -Resveratrol prolonged lifespan in the GRZ strain, but not in the MZM0410 strain. -Rapamycin mixed with the food inhibited TOR activity, but did not prolong lifespan in either strain. The different response of the two strain to the treatments were surprising and led us to further investigate the fast-aging phenotype of the GRZ strain as compared to the MZM-0410 strain. We analyzed the captive lifespan of wild-derived strains originating from the entire distribution range of N. furzeri, including the region from where the GRZ stain was originally isolated and found that no wild-derived strain shows a lifespan of ~3 months. We conclude that that GRZ phenotype is not a natural phenotype. In addition, we found that the GRZ shows accelerated onset of age-related neoplasias. Finally, we characterized the adult neuronal stem cells of N. furzeri in relation to their localization, the effects of aging and expression of selected microRNAs.
Publications
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Effects of dietary restriction on mortality and age-related phenotypes in the short-lived fish Nothobranchius furzeri. Aging Cell. 2009 Apr;8(2):88-99
Terzibasi E, Lefrangois C, Domenici P, Hartmann N, Graf M, Cellerino A
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The short-lived annual fish Nothobranchius furzeri shows a typical teleost aging process reinforced by high incidence of age-dependent neoplasias. Exp Gerontol. 2011 Apr;46(4):249-56
Di Cicco E, Terzibasi Tozzini E, Rossi G, Cellerino A
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Adult neurogenesis in the shortlived teleost Nothobranchius furzeri: localization of neurogenic niches,molecular characterization and effects of aging. Aging Cell. 2012 Apr;11(2):241-51
Terzibasi Tozzini E, Baumgart M, Battistoni G, Cellerino A
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Brain derived neurotrophic factor: mRNA expression and protein distribution in the brain of the teleost Nothobranchius furzeri. J Comp Neurol. 2013 Aug 24 [Epub ahead of print]
D'Angelo L, de Girolamo P, Lucini C, Terzibasi Tozzini E, Baumgart M, Castaldo L, Cellerino A
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Parallel evolution of senescence in annual fishes in response to extrinsic mortality. BMC Evol Biol. 2013 Apr 3;13:77
Terzibasi Tozzini E, Dorn A, Ng'oma E, Polacik M, Blazek R, Reichwald K, Petzold A, Watters B, Reichard M, Cellerino A
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Regulation of microRNA expression in the neuronal stem cell niches during aging of the short-lived annual fish Nothobranchius furzeri. Frontiers in Cellular Neuroscience. 2014 Feb 5. 8:51
Terzibasi Tozzini E, Savino A, Ripa R, Battistoni G, Baumgart M and Cellerino A
