The proteasome, which digests used-up, ubiquitinated proteins in implementing cellular protein turnover, can be treated with oleuropein from extra virgin olive oil or olive fruit.
Carnosine helps reverse proteasomal decline and protects proteins from carbonylation that can jam proteasomes. Proteasomes can be clogged by a diet rich in arachidonic acid, and are better preserved by caloric restricted diets [Gaczynska M, Osmulski PA, Ward WF, 2001].
There are also indications that the proteasome can be fouled by advanced glycation end products. Carbonylated proteins can interfere with the proteasome. [R.Gonzalez-Dosal, MD Sorensen, B.F.C. Clark, S. Rattan, P. Kristensen, 2006]. "By inhibiting the proteasome, carbonylated proteins could interfere with cell cycle progression and control.... Protein carbonylation thus becomes a potentially terminal condition." - LifeExtension, 2001.
Furthermore, there is evidence that the proteasome can be degraded by the lipid oxidation product 4-hydroxy-2-nonenal [B.Friguet, 2002], and degradation of proteasome performance by cell loading with ceroid (lipofuscin originating in alcholic wastes) or lipofuscin has also been demonstrated.
It is also known that the glycooxidation product carboxymethyllysine inactivates the 26s proteasome. (See the formation of carboxymethyllysine.) Partial inhibition of proteasomes in young cells can lead to cellular senescence [N Chondrogianni, FLL Stratford, IP Trougakos, B Friguet, AJ Rivett, ES Gonos, 2003].
"We demonstrate that oleuropein, the major constituent of Olea europea leaf extract, extra virgin olive oil and olives, enhances the proteasome activities in vitro stronger than other known chemical activators, possibly through conformational changes of the proteasome.
Moreover,continuous treatment of early passage human embryonic fibroblasts with oleuropein decreases the intracellular levels of reactive oxygen species (ROS), reduces the amount of oxidized proteins through increased proteasome-mediated degradation rates and retains proteasome function during replicative senescence.
Importantly, oleuropein-treated cultures exhibit a delay in the appearance of senescence morphology and their life span is extended by approximately 15%." - [M Katsiki, N Chondrogianni, I Chinou, AJ Rivett, ES Gonos, 2007].
Note that this partly explains the good results obtained by Jeanne Calment with olive oil as a skin rub and tends to promote extra virgin olive oil as a salad dressing component.
Also see Olive Oil, health benefits, antioxidant hydroxytyrosol, squalene, oleic acid.
Testing the garbage accumulation theory of ageing: mitotic activity protects cells from death induced by inhibition of autophagy by Yuri Stroikin, Helge Dalen, Ulf T. Brunk and Alexei Terman, Biogerontology, Vol.6, No.1, Jan 2005.
Accumulation of garbage such as lipofuscin eventually results in cell death by apoptosis. The removal of oxidatively damaged cellular structures and garbage usually takes place via lysosomes, proteasomes, and cytosolic proteases, but this is inherently imperfect. Accumulation of lipofuscin and damaged mitochondria leads to enhancement of oxidative stress and damage to cellular DNA. Proteasome activity could be enhanced by repeated mild heat shock with life-extending effect.
See also Enhancing proteasome activity. Note that defective proteasome function is viewed as a causal factor in the cellular degeneration occurring in neurodegenerative disorders [AL Bulteau, B Friguet, 2004], and amyloid beta has been shown to inhibit proteasome activity in Alzheimer's Disease [ S Ohb, HS Honga, E Hwanga, HJ Simb, W Leec, SJ Shina, I Mook-Jung, 2005].
Certainly resveratrol, which prevents accumulation of amyloid beta, could be useful in preserving proteasome function. Note that the failure of proteasomes results in the accumulation of damaged proteins into Lewis bodies often seen in Parkinson's disease, senile dementia, and some forms of Alzheimer's Disease.
