INCREASED TRANSCRIPTION OF THE ASTROCYTE GENE GFAP DURING MIDDLE-AGE IS ATTENUATED BY FOOD RESTRICTION - IMPLICATIONS FOR THE ROLE OF OXIDATIVE STRESS

Glial fibrillary acidic protein (GFAP)? an intermediate filament of as trocytes, shows increased expression during aging, Because we found th at chronic food restriction retards the increase of GFAP mRNA in aging rats and because food restriction decreases the load of oxidized prot eins and lipids in association with increased life span, we investigat ed the regulation of GFAP during oxidative stress and aging. First, we showed that food restriction decreased the transcription of GFAP in a ging rats. This result generalizes effects of food restriction on age changes of transcription; whether transcription decreases during aging as in hepatic genes, or increases during aging as in astrocytic GFAP, food restriction attenuates the age change, Moreover, food restrictio n decreased microglial activation during aging, which suggested the hy pothesis that GFAP expression is sensitive to oxidative stress. Becaus e GFAP transcription in cultured glia is increased by oxidative stress in response to hydrogen peroxide and cysteamine whether or not microg lia were present, we conclude that responses of GFAP to oxidative stre ss in astrocytes do not depend on microglial activation. The results i mplicate oxidative stress in the increased expression of GFAP during a ging, but also in responses to brain injury. Published bf Elsevier Sci ence Inc.