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Enhanced glycogenesis is involved in cellular senescence via GSK3/GS modulation.

Authors
Seo, YH; Jung, HJ; Shin, HT; Kim, YM; Yim, H; Chung, HY; Lim, IK; Yoon, G
Citation
Aging cell, 7(6):894-907, 2008
Journal Title
Aging cell
ISSN
1474-97181474-9726
Abstract
Glycogen biogenesis and its response to physiological stimuli have often been implicated in age-related diseases. However, their direct relationships to cell senescence and aging have not been clearly elucidated. Here, we report the central involvement of enhanced glycogenesis in cellular senescence. Glycogen accumulation, glycogen synthase (GS) activation, and glycogen synthase kinase 3 (GSK3) inactivation commonly occurred in diverse cellular senescence models, including the liver tissues of aging F344 rats. Subcytotoxic concentrations of GSK3 inhibitors (SB415286 and LiCl) were sufficient to induce cellular senescence with increased glycogenesis. Interestingly, the SB415286-induced glycogenesis was irreversible, as were increased levels of reactive oxygen species and gain of senescence phenotypes. Blocking GSK3 activity using siRNA or dominant negative mutant (GSK3beta-K85A) also effectively induced senescence phenotypes, and GS knock-down significantly attenuated the stress-induced senescence phenotypes. Taken together, these results clearly demonstrate that augmented glycogenesis is not only common, but is also directly linked to cellular senescence and aging, suggesting GSK3 and GS as novel modulators of senescence, and providing new insight into the metabolic backgrounds of aging and aging-related pathogenesis.
MeSH terms
Age FactorsAminophenols/pharmacologyAnimalsCell Aging/drug effectsCell Aging/physiology*Cell LineDose-Response Relationship, DrugGlycogen/biosynthesis*Glycogen/metabolismGlycogen Synthase/deficiencyGlycogen Synthase/geneticsGlycogen Synthase/metabolismGlycogen Synthase/physiology*Glycogen Synthase Kinase 3/antagonists & inhibitorsGlycogen Synthase Kinase 3/physiology*HumansMaleMaleimides/pharmacologyRatsRats, Inbred F344
DOI
10.1111/j.1474-9726.2008.00436.x
PMID
18782348
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
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김유미임현이임인경윤계순
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