Diminished Proteasomal Activity Causes Accelerated Aging

The proteasome is a cellular repair system that seems to be important in the evolution of longevity; here researchers show that impairing it causes accelerating aging. This is expected - aging is damage. Even if it fits with the established view, however, we should be wary of putting too much weight on studies that show shortened life span. There are all too many ways to reduce life span that have no application to extending life span, and the true proof of an interesting mechanism is to demonstrate increased maximum life span in mammals. Still, this is interesting work when held up against the broader context of what is known about the proteasome and the role of low level biochemical damage in aging: "The proteasome is a multicatalytic enzyme complex responsible for the degradation of both normal and damaged proteins. An age-related decline in proteasomal activity has been implicated in various age-related pathologies, including obesity and hepatic steatosis. The relevance of decreased proteasomal activity to aging and age-related diseases remains unclear, however, because suitable animal models are not available. In the present study, we established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity. Tg mice exhibited a shortened life span and developed age-related phenotypes. In Tg mice, polyubiquitinated and oxidized proteins accumulated. ... Our results provide the first in vivo evidence that decreased proteasomal chymotrypsin-like activity affects longevity and aggravates age-related metabolic disorders, such as obesity and hepatic steatosis."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22210478


Surprising since a number of common flavonoids reduce proteasomal activity.

Posted by: Lou Pagnucco at January 3rd, 2012 1:19 PM
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