Ascorbic acid deficiency accelerates aging of hepatic stellate cells with up-regulation of PPARγ.

Senescent cells have been observed in certain aged or damaged tissues. However, the information about the effects of aging on liver cells is limited. In the present study, we have examined age-related histological changes in the livers of senescence marker protein knockout (SMP30-/-) mice, which are considered as a murine aging model due to the more sensitive response to apoptotic reagents and due to their shorter life span. In livers of old SMP30-/- mice, numerous hepatic stellate cells (HSCs) were hypertrophic and contained abundant microvesicular lipid droplets in cytoplasm. We have found that the expression of peroxisome proliferators-activated receptor γ (PPARγ), which is a protein related to lipid metabolism and HSC quiescence, was increased in hypertrophic HSCs by aging and vitamin C (VC) deficiency, whereas these phenomena were dramatically reduced by antioxidant treatment. Therefore, these prominent phenotypic changes can be considered as aging markers in the livers of animals which are subjected to antioxidant property evaluation.