2016
DOI: 10.18632/aging.101011
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Abstract: Isoketals (IsoKs) are highly reactive γ-ketoaldehyde products of lipid peroxidation that covalently adduct lysine side chains in proteins, impairing their function. Using C. elegans as a model organism, we sought to test the hypothesis that IsoKs contribute to molecular aging through adduction and inactivation of specific protein targets, and that this process can be abrogated using salicylamine (SA), a selective IsoK scavenger. Treatment with SA extends adult nematode longevity by nearly 56% and prevents mult… Show more

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Cited by 20 publications
(95 citation statements)
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References 93 publications
(95 reference statements)
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“…In Figure 2 bottom, the list of pathways/clusters, and the details of the largest pathway are zoomed in. Regarding the first pathway, rapamycin reduces ets-7 transcription, which was shown to be necessary for the healthspan-promoting effects of salicylamine [ 54 ]. Furthermore, rapamycin upregulates the transcription factor daf-16 (a homolog to Foxo) and downregulates the daf-16 inhibitors akt-1 and akt-2, putatively leading to an improved stress- and immune-response and prolonged lifespan via the Insulin/IGF-1 pathway [ 55 ].…”
Section: Resultsmentioning
confidence: 99%
“…While LDEs are known contributors to spontaneous proteome damage during organismal ageing, any investigation of the potential for carbonyl scavengers to afford health benefits by suppressing such damage are complicated by the complexities and cost of performing lifespan extension studies in mammalian species. In recent times, the emergence of experimental approaches involving "simple" model organisms with short lifespans have allowed novel investigations of the effects of carbonyl-scavengers on the functional deficits that accompany ageing [79,80].…”
Section: Novel Cytoprotective Properties Of Hydralazinementioning
confidence: 99%
“…The nematode worm C. elegans (with an average adult lifespan of less than 3 weeks) is often used as a rapid in vivo model of aging. In N2 wild-type adult worms treated with 2-HOBA, median lifespan is increased 56% [140]. The precise mechanisms whereby 2-HOBA increases longevity need to be determined.…”
Section: Reactive Carbonyl Species Scavengers Ameliorate Diseasementioning
confidence: 99%
“…The precise mechanisms whereby 2-HOBA increases longevity need to be determined. However, 2-HOBA treatment fails to extend lifespan in worms where the gene for sirtuin SIR-2.1 is knocked out, suggesting that RCS modification of this deacetylase might be a major factor decreasing longevity [140]. Future studies are needed to determine if 2-HOBA and other 2-aminomethylphenols such as PPM will increase lifespan in mammals.…”
Section: Reactive Carbonyl Species Scavengers Ameliorate Diseasementioning
confidence: 99%
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