Increase of oxidatively modified protein is associated with a decrease of proteasome activity and content in aging...

Area of Science:

• Cellular biology
• Dermatology
• Biochemistry

Background:

• The aging process involves cellular damage and impaired protein homeostasis.
• The proteasome is crucial for degrading damaged proteins.

Purpose of the Study:

• To investigate the role of proteasome function in epidermal cell aging.
• To determine if proteasome activity declines with age and replicative senescence.

Main Methods:

• Assaying modified protein levels (oxidized, glycated, 4-hydroxy-2-nonenal) in epidermal cells from donors of varying ages.
• Measuring proteasome activity (chymotrypsin-like, peptidylglutamyl-peptide hydrolase) and content via immunoblotting and ELISA.
• Assessing proteasome function in cultured keratinocytes during serial passaging.
• Correlating proteasome content with the aging marker senescence-associated β-galactosidase.

Main Results:

• Epidermal cells from older donors exhibited higher levels of oxidized, glycated, and 4-hydroxy-2-nonenal-modified proteins.
• Proteasome activity, specifically chymotrypsin-like and peptidylglutamyl-peptide hydrolase, decreased in aging keratinocytes.
• A reduction in proteasome content was observed in aging cells, correlating with decreased activity.
• Serial passaging of keratinocytes led to decreased proteasome activity and content.
• An inverse relationship was found between senescence-associated β-galactosidase and proteasome content in both cell cultures and skin.

Conclusions:

• Proteasome function is downregulated in aging epidermal cells both in vivo and in vitro.
• This age-related decline in proteasome activity contributes to the accumulation of modified proteins.
• Proteasome downregulation is associated with replicative senescence and cellular aging in keratinocytes.