2014
DOI: 10.18632/aging.100683
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Abstract: The ketone body beta-hydroxybutyrate (βHB) is a histone deacetylase (HDAC) inhibitor and has been shown to be protective in many disease models, but its effects on aging are not well studied. Therefore we determined the effect of βHB supplementation on the lifespan of C. elegans nematodes. βHB supplementation extended mean lifespan by approximately 20%. RNAi knockdown of HDACs hda-2 or hda-3 also increased lifespan and further prevented βHB-mediated lifespan extension. βHB-mediated lifespan extension required … Show more

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Cited by 125 publications
(109 citation statements)
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References 100 publications
(132 reference statements)
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“…Following bleach synchronization, roughly 40 C. elegans eggs were placed in each of six 3 μm cell culture inserts, which were placed in shaken 6-well microplates with liquid S-medium containing 9 × 10 10 heat-killed HT115(DE3) E. coli per ml as described in (Edwards et al 2014). 3 of the wells were treated from the beginning of the lifespan with either 10 mM cytidine ( n = 163 worms) or 10 mM hypoxanthine ( n =366 worms) while the other 3 wells were left untreated as controls ( n =349 worms for the hypoxanthine control and n =112 worms for the cytidine control).…”
Section: Methodsmentioning
confidence: 99%
See 1 more Smart Citation
“…Following bleach synchronization, roughly 40 C. elegans eggs were placed in each of six 3 μm cell culture inserts, which were placed in shaken 6-well microplates with liquid S-medium containing 9 × 10 10 heat-killed HT115(DE3) E. coli per ml as described in (Edwards et al 2014). 3 of the wells were treated from the beginning of the lifespan with either 10 mM cytidine ( n = 163 worms) or 10 mM hypoxanthine ( n =366 worms) while the other 3 wells were left untreated as controls ( n =349 worms for the hypoxanthine control and n =112 worms for the cytidine control).…”
Section: Methodsmentioning
confidence: 99%
“…Despite these advancements in the field, there have been few global proteomic investigations of the C. elegans aging process, and even fewer metabolomic investigations of aging. Based on our previous findings regarding the role that dietary metabolites play in C. elegans lifespan extension and in an effort to add to the understanding of aging in this model organism (Edwards et al 2015; Edwards et al 2014; Edwards et al 2013), we chose to employ a mass spectroscopy-based approach to global endogenous metabolite identification in young versus aged C. elegans . We also pursued a mass spectrometry-based heavy isotope labeling approach for global protein quantification, with the goal of contextualizing the results from both “–omic” investigations using the C. elegans aging literature.…”
Section: Introductionmentioning
confidence: 99%
“…Furthermore, the ketone body D-β-hydroxybutyrate (β-OHB) (FIG. 5b) is a histone deacetylase inhibitor that was shown to extend lifespan in C. elegans , possibly through activating the SIR-2.1, AMPK, DAF-16–FOXO and SKN-1–NRF pathways 127 . The potential health benefits of β-OHB may be at least partially attributed to its ability to suppress oxidative stress by mediating increased histone acetylation at the FOXO3A and metallothionein 2 ( MT2 ) promoters 128 .…”
Section: Strategies For Improving Healthspanmentioning
confidence: 99%
“…The inflammasome activates inflammatory caspase and cytokines of the IL-1 family within a complex of proteins involved in inflammation and apoptosis. 38 The inflammasome has been seen as a natural immunity system that protects living organisms against alien substances and pathogenic microorganisms.…”
Section: Suppression Of Inflammasomementioning
confidence: 99%