Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1.
Level 5 - mechanism / opinion, no new human data
Bench, in vitro enzymatic assays, and yeast model research without human clinical data.
PubMed 12297502 · doi:10.1074/jbc.M205670200
What was done
Investigated the effect of nicotinamide on yeast (*Saccharomyces cerevisiae*) transcriptional silencing, rDNA recombination, replicative life span, and Sir2 localization. Measured the in vitro enzymatic inhibition kinetics and IC50 of nicotinamide against yeast Sir2 and human SIRT1 histone deacetylases.
What was found
Nicotinamide inhibited yeast silencing, elevated rDNA recombination, and shortened yeast replicative life span to match that of a *sir2* null mutant. It caused delocalization of Sir2 even in G1-arrested yeast cells. In vitro, physiological concentrations of nicotinamide noncompetitively inhibited both yeast Sir2 and human SIRT1 with an IC50 < 50 µM, matching or exceeding known synthetic inhibitors.
Why it matters
Demonstrates that nicotinamide acts as an endogenous feedback inhibitor of Sir2 family deacetylases, establishing a direct biochemical link between NAD+ metabolism, heterochromatin maintenance, and cellular longevity.
Limits
All findings are based solely on in vitro enzymatic assays and yeast models; no mammalian in vivo or human data were evaluated. The abstract reports no exact lifespan curve statistics, variance metrics, or numerical recombination rates.
Cited by
- supports Unstabilized NR and NMN degrade into nicotinamide at room temperature, and high doses of nicotinamide inhibit sirtuins and PARP and impair DNA repair.