Extremely Long-Lived Proteins May Provide Insight into Cell Aging

One of the big mysteries in biology is why cells age. Now scientists at the Salk Institute for Biological Studies report that they have discovered a weakness in a component of brain cells that may explain how the aging process occurs in the brain. The scientists discovered that certain proteins, called extremely long-lived proteins (ELLPs), which are found on the surface of the nucleus of neurons, have a remarkably long lifespan. While the lifespan of most proteins totals two days or less, the Salk Institute researchers identified ELLPs in the rat brain that were as old as the organism, a finding they reported on February 2, 2012 in Science. The Salk scientists are the first to discover an essential intracellular machine whose components include proteins of this age. Their results suggest the proteins can last an entire lifetime, without being replaced. ELLPs make up the transport channels on the surface of the nucleus; gates that control what materials enter and exit. Their long lifespan might be an advantage if not for the wear-and-tear that these proteins experience over time. Unlike other proteins in the body, ELLPs are not replaced when they incur aberrant chemical modifications and other damage. Damage to the ELLPs weakens the ability of the three-dimensional transport channels that are composed of these proteins to safeguard the cell's nucleus from toxins, says Dr. Martin Hetzer, a professor in Salk's Molecular and Cell Biology Laboratory, who headed the research. These toxins may alter the cell's DNA and thereby the activity of genes, resulting in cellular aging. Funded by the Ellison Medical Foundation and the Glenn Foundation for Medical Research, Dr. Hetzer's research group is the only lab in the world that is investigating the role of these transport channels, called the nuclear pore complex (NPC), in the aging process.
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