Rapid reversion of aging phenotypes by nicotinamide through possible modulation of histone acetylation.
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.
Matuoka
K
K
Institute of Medical Science, University of Tokyo, Japan. kmatuoka@mailhost.net
Chen
K Y
KY
Takenawa
T
T
D000107:Acetylation / Q000187:drug effects; D000123:Acetyltransferases / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009243:NAD / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009525:Niacin; D009536:Niacinamide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D010641:Phenotype; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D029701:Saccharomyces cerevisiae Proteins; D001616:beta-Galactosidase / Q000378:metabolism
D000975:Antioxidants; D004791:Enzyme Inhibitors; D006657:Histones; D016877:Oxidants; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D029701:Saccharomyces cerevisiae Proteins; D009243:NAD; D009536:Niacinamide; D009525:Niacin; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D001616:beta-Galactosidase; D006655:Histone Deacetylases