Model of Protein Charge Predicts Aging Associated Proteins

Researchers here use a model to predict aging-associated proteins, those in which damaged and misfolded molecules are noticeable prevalent in aged tissues. Since the model turns up proteins already known to be associated with aging, some of the others in the list may also be worth looking at, and the overall effort can be taken as supporting evidence for some theories on the relative importance of various mechanisms in aging:

Certain proteins known to be associated with aging and age-related diseases such as Alzheimer's disease and cancer are also at a high risk for destabilization caused by oxidation. This finding provides an understanding of how oxidative damage, which is a natural process in aging cells, affects proteins. It could also prove to be a foundation to a better understanding of age-related diseases. When people turn about 80 years of age, approximately half of the body's proteins are damaged by oxidation. Oxidation occurs because of random chemical degradations that are associated with converting food to energy in the presence of oxygen. Oxidation in the human body, mediated by free radicals, damages cellular proteins, lipids, DNA, and other cellular structures that contribute to disease processes.

Researchers used physics principles and computer analysis to evaluate protein electrostatics, or charges. They found that short, highly charged proteins are particularly susceptible to large destabilization and that even a single oxidation event within these proteins is sufficient to unfold its normally balled-up, folded structure. "Our paper explains the molecular mechanism by which natural chemical processes of aging affect our proteins. Our method predicts which proteins are the most at risk of unfolding when they get damaged. We then applied the principle in searching protein databases. Interestingly, we found that the proteins most at-risk for oxidative unfolding included 20 proteins that span a wide-spectrum of functionalities, all of which had been known by researchers previously to be associated with aging." The list of proteins includes telomerase proteins, which play a major role in aging of cells and cancer development by the extending of telomeres; and histones, which are DNA-binding proteins known to be relevant for many processes, including memory loss and cancer. The research could be a first step toward finding other proteins, not currently suspected, that are susceptible to high oxidation, instability and age-related diseases. The proteins could prove to be the key to targeted treatments against certain age-related diseases.



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