Proteasome Activity and Content Decrease in Aged Skin and Up‐Regulation of Proteasome Subunits Reduces aging markers in the Dermal Fibroblast from the Elderly

In aged cells, the age‐related oxidized proteins is accumulated that indicates defects in the proteolytic machinery could contribute to the decline of protein turnover. Proteasome is the multicatalytic proteinase complex, which plays a central role in protein degradation. Recently aged‐related proteasome malfunction has been studied in replicative senescent lung fibroblasts. However, the change of proteasome activity and detail proteasome subunits in skin aging process has not yet been studied. To study the role of proteasome in skin aging we investigated proteasome activity and the level of oxidized proteins and proteasome subunits in the dermal fibroblasts from individuals ranging from 10 to 86 years of age. The proteasome activity changed with age in a biphasic manner, significantly decreasing to 50 years old and showing no change over 50 to 80 years old. Proteosome activity also showed a passage‐dependent biphasic change in replicative senescent human skin fibroblasts. We also confirmed that proteasome activity consists with the accumulation of oxidized and ubiqutinated protein. We observed declined proteasome activity is associated with the decrease of the expression of prteasome catalytic subunits (PSMB1 and PSMB5) and 19S regulatory subunits in aging skin fibroblasts. Finally, we found that up‐regulation of PSMB1 or PSMB5 in skin fibroblast from the elderly using Lenti‐virus gene delivery system decrease the aging markers, such as β‐gal staining, lipofuscin and p21 expression. Taken together, these findings suggest that malfunction of proteasome may contribute to aging process in the human skin and sustenance of normal proteasome activity could prevent or delay skin aging.