SIRT1 stimulation by polyphenols is affected by their stability and metabolism
Language: 
English
Abstract: 

Silent information regulator two ortholog 1 (SIRT1) is the human ortholog of the yeast sir2 protein; one of the most important regulators of lifespan extension by caloric restriction in several organisms. Dietary polyphenols, abundant in vegetables, fruits, cereals, wine and tea, were reported to stimulate the deacetylase activity of recombinant SIRT1 protein and could therefore be potential regulators of aging associated processes. However, inconsistent data between effects of polyphenols on the recombinant SIRT1 and on in vivo SIRT1, led us to investigate the influence of (1) stability of polyphenols under experimental conditions and (2) metabolism of polyphenols in human HT29 cells, on stimulation of SIRT1. With an improved SIRT1 deacetylation assay we found three new polyphenolic stimulators. Epigallocatechin galate (EGCg, 1.76-fold), epicatechin galate (ECg, 1.85-fold) and myricetin (3.19-fold) stimulated SIRT1 under stabilizing conditions, whereas without stabilization, these polyphenols strongly inhibited SIRT1, probably due to H2O2 formation. Using metabolically active HT29 cells we were able to show that quercetin (a stimulator of recombinant SIRT1) could not stimulate intracellular SIRT1. The major quercetin metabolite in humans, quercetin 3-O-glucuronide, slightly inhibited the recombinant SIRT1 activity which explains the lack of stimulatory action of quercetin in HT29 cells. This study shows that the stimulation of SIRT1 is strongly affected by polyphenol stability and metabolism, therefore extrapolation of in vitro SIRT1 stimulation results to physiological effects should be done with caution.

Author(s): 
de Boer, Vincent C. J.
de Goffau, Marcus C.
Arts, Ilja C. W.
Hollman, Peter C. H.
Keijer, Jaap
Item Type: 
Journal Article
Publication Title: 
Mechanisms of Ageing and Development
Journal Abbreviation: 
Mech. Ageing Dev.
Publication Date: 
2006-07
Publication Year: 
2006
Pages: 
618-627
Volume: 
127
Issue: 
7
ISSN: 
0047-6374
DOI: 
10.1016/j.mad.2006.02.007
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 16603228

Turabian/Chicago Citation

Vincent C. J. de Boer, Marcus C. de Goffau, Ilja C. W. Arts, Peter C. H. Hollman and Jaap Keijer. 2006-07. "SIRT1 stimulation by polyphenols is affected by their stability and metabolism." Mechanisms of Ageing and Development 127: 7: 618-627. 10.1016/j.mad.2006.02.007.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.mad.2006.02.007 | issn = 0047-6374 | volume = 127 | pages = 618-627 | last = de Boer | first = Vincent C. J. | coauthors = de Goffau, Marcus C., Arts, Ilja C. W., Hollman, Peter C. H., Keijer, Jaap | title = SIRT1 stimulation by polyphenols is affected by their stability and metabolism | journal = Mechanisms of Ageing and Development | date = 2006-07 | pmid = | pmc = }} </ref>