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Diet-derived advanced glycation end products or lipofuscin disrupts proteostasis and reduces life span in Drosophila melanogaster

Tsakiri, Eleni N., Iliaki, Kalliopi K., Höhn, Annika, Grimm, Stefanie, Papassideri, Issidora S., Grune, Tilman, Trougakos, Ioannis P.·2013·Free Radical Biology and Medicine
DOI 10.1016/j.freeradbiomed.2013.08.186
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Abstract

Advanced glycation end product (AGE)-modified proteins are formed by the nonenzymatic glycation of free amino groups of proteins and, along with lipofuscin (a highly oxidized aggregate of covalently cross-linked proteins, sugars, and lipids), have been found to accumulate during aging and in several age-related diseases. As the in vivo effects of diet-derived AGEs or lipofuscin remain elusive, we sought to study the impact of oral administration of glucose-, fructose-, or ribose-modified albumin or of artificial lipofuscin in a genetically tractable model organism. We report herein that continuous feeding of young Drosophila flies with culture medium enriched in AGEs or in lipofuscin resulted in reduced locomotor performance and in accelerated rates of AGE-modified proteins and carbonylated proteins accumulation in the somatic tissues and hemolymph of flies, as well as in a significant reduction of flies health span and life span. These phenotypic effects were accompanied by reduced proteasome peptidase activities in both the hemolymph and the somatic tissues of flies and higher levels of oxidative stress; furthermore, oral administration of AGEs or lipofuscin in flies triggered an upregulation of the lysosomal cathepsin B, L activities. Finally, RNAi-mediated cathepsin D knockdown reduced flies longevity and significantly augmented the deleterious effects of AGEs and lipofuscin, indicating that lysosomal cathepsins reduce the toxicity of diet-derived AGEs or lipofuscin. Our…

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Metadata

Authors
Tsakiri, E. N., Iliaki, K. K., Höhn, A., Grimm, S., Papassideri, I. S., Grune, T., & Trougakos, I. P.
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2013-12
Volume
65
Pages
1155-1163
ISSN
0891-5849
DOI
10.1016/j.freeradbiomed.2013.08.186
Cited by
64
References
3
Language
en
Licence
Funders
EU-FP7 Capacities (REGPOT-CT-2011-284460)

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CoChat. (2026). Citation check: Diet-derived advanced glycation end products or lipofuscin disrupts proteostasis and reduces life span in Drosophila melanogaster. https://app.cochat.ai/papers/10.1016/j.freeradbiomed.2013.08.186
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Tsakiri, E. N., Iliaki, K. K., Höhn, A., Grimm, S., Papassideri, I. S., Grune, T., & Trougakos, I. P. (2013). Diet-derived advanced glycation end products or lipofuscin disrupts proteostasis and reduces life span in Drosophila melanogaster. Free Radical Biology and Medicine. https://doi.org/10.1016/j.freeradbiomed.2013.08.186