From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Thu Jul 18 2002 - 06:13:58 MDT
Title
Rapid reversion of aging phenotypes by nicotinamide through possible
modulation of histone acetylation.
Source
Cellular & Molecular Life
Sciences. 58(14):2108-16, 2001 Dec.
Abstract
Aging appears to be an irreversible process. Here we report that nicotinamide
(NAA) can induce rapid and reversible reversion of aging phenotypes in human
diploid fibroblasts in terms of cell morphology and senescence-associated
beta-galactosidase activity. Although NAA seems to enhance the replicative
potential of the cells, it has little effect on their growth rate and
life span, suggesting that NAA action is rather separated
from the cellular replicative system. The effects are unique
to NAA: none ofthe NAA-related compounds examined (an NAD precursor/niacin,
NAD analogs, and poly(ADP-ribose) polymerase inhibitors) exerted similar
effects. Thus, NAD-related metabolism and poly(ADP-ribosyl)ation are unlikely
related to the NAA action. On the other hand, histone acetyltransferase (HAT)
activity was elevated in NAA-exposed cells, while in aged cells, HAT activity
and histone H4 acetylation were lowered. Taken together, the results suggest
that NAA may cause rejuvenation by restoring, at least in part, altered gene
expression in aged cells through its activation of HAT.
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