2013
DOI: 10.18632/aging.100548
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Abstract: Compounds that delay aging in model organisms may be of significant interest to anti-aging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. We here aimed to test whether pharmaceutical concentrations of three fibrates, pharmacologically established serum lipid-lowering drugs and ligands of the nuclear receptor PPARalpha in mammals, are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditi… Show more

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Cited by 20 publications
(52 citation statements)
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References 26 publications
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“…Further discrepancies regarding the function and regulation of lipids in humans and C. elegans are summarized in Mullaney and Ashrafi [ 83 ]. Nevertheless, and quite surprisingly, numerous key components, functions and regulatory pathways regarding lipid metabolism are indeed comparable in C. elegans : Similarities in the regulation of membrane fluidity [ 84 ], of fat depletion after consumption of oats [ 85 ], legumes [ 86 ], and fibrates [ 87 ] as well as after exercise [ 88 ], and in the genetic background of obesity [ 89 91 ] and fat storage [ 92 ] are only a few examples. The adult worm is post-mitotic [ 93 ] but also many human diseases and cell senescence processes are associated with tissues that no longer divide, e.g., in the brain [ 94 , 95 ].…”
Section: Resultsmentioning
confidence: 99%
“…Further discrepancies regarding the function and regulation of lipids in humans and C. elegans are summarized in Mullaney and Ashrafi [ 83 ]. Nevertheless, and quite surprisingly, numerous key components, functions and regulatory pathways regarding lipid metabolism are indeed comparable in C. elegans : Similarities in the regulation of membrane fluidity [ 84 ], of fat depletion after consumption of oats [ 85 ], legumes [ 86 ], and fibrates [ 87 ] as well as after exercise [ 88 ], and in the genetic background of obesity [ 89 91 ] and fat storage [ 92 ] are only a few examples. The adult worm is post-mitotic [ 93 ] but also many human diseases and cell senescence processes are associated with tissues that no longer divide, e.g., in the brain [ 94 , 95 ].…”
Section: Resultsmentioning
confidence: 99%
“…Although no definitive PPAR homolog in C. elegans is known, it has a large number of nuclear hormone receptor (‘nhr’) genes with at least modest homology to PPARγ . Specifically, one study suggested that the effect of fibrates depended on intact nuclear hormone receptor (nhr-49) (Brandstadt et al, 2013). Further, our treatment of nematodes with fenofibrate resulted in dramatic decrease in worm fat content, a phenomenon predicted to result from its PPAR agonist activity.…”
Section: Resultsmentioning
confidence: 99%
“…Here a clear cluster emerged of four compounds that had both low total numbers of side effects and low maximum likelihoods of causing a side effect, while maintaining moderate lifespan extending potential. These geroprotectors included the autophagy inducer spermidine (Eisenberg et al 2009 ), the polyphenol gallic acid (Saul et al 2011 ), the glycolysis inhibitor d -glucosamine (Weimer et al 2014 ), and the lipid-lowering PPAR agonist clofibrate (Brandstädt et al 2013 ) (Fig. 4 b).…”
Section: Resultsmentioning
confidence: 99%