Introduction:

The ubiquitin-proteasome system participates in the regulation of essential cellular processes, such as apoptosis and anti-oxidant response, which contribute to cardiac aging. However, the effect of aging on proteasome function in the mammalian heart is poorly understood.

Objective:

Aim of the study was to identify whether proteasome function is altered during aging in murine hearts.

Methods:

Proteasome activities and assembly in hearts of two age groups of male mice (17±1 vs. 113±9 weeks; mean±SEM; n=5) were compared in a blinded study.

Results:

Heart weight and heart weight to body weight ratio were not different between the two age groups. Remarkably, the ATP-dependent chymotrypsin-like 26S proteasome activity was 84±12% (mean±SEM) higher in aging hearts (p=0.002), whereas there was only a trend towards an increase in the corresponding 20S proteasome activity (+27±13%, p=0.1). Analysis of assembled proteasome subunits with proteolytic activity via fluorescent probes indicated a trend towards increased incorporation of 20S subunits with chymotrypsin-like activity (+41±16%, p=0.06) into proteasomes, supporting the observation made in the 20S proteasome assay. These results suggest that aging alters the composition of cardiac 20S proteasome subpopulations. Overall, incorporation of proteolytic 20S subunits into proteasome complexes was unchanged, indicating that the significantly increased 26S chymotrypsin-like activity was regulated at the 19S proteasome level (26S complexes = 19S + 20S). In conclusion, 26S proteasome function is associated with aging in murine hearts. Additional studies will reveal whether this functional alteration of proteasome complexes has a causal role in cardiac aging and function.