Northwestern University scientists have shown that elevated levels of special protective proteins that respond to stress in a cell (known as molecular chaperones) promote longevity. Acute stress triggers a cascading reaction inside cells that results in the repair or elimination of misfolded proteins, prolonging life by preventing or delaying cell damage.
The findings are published online today (Dec. 10) by Molecular Biology of the Cell, a publication of the American Society for Cell Biology. The article will appear in print in the journal's February 2004 issue.
"Sustained stress definitely is not good for you, but it appears that an occasional burst of stress or low levels of stress can be very protective," said Richard I. Morimoto, John Evans Professor of Biology, who co-authored the paper with lead author James F. Morley, a graduate student in Morimoto's lab. "Brief exposure to environmental and physiological stress has long-term benefits to the cell because it unleashes a great number of molecular chaperones that capture all kinds of damaged and misfolded proteins."
Stressors also include elevated temperatures, oxygen stress, bacterial and viral infections, and exposure to toxins such as heavy metals, all of which challenge the environment of the cell. A master protein called heat shock factor senses the stress and responds by turning on the genes that encode molecular chaperones.
Proteins are basic components of all living cells. To do its job properly, each protein first must fold itself into the proper shape. In this process, the protein is assisted by molecular chaperones that function to prevent misfolding, or, in the case of already misfolded proteins, to detect them and prevent their further accumulation. Mutations or environmental stress enhances protein damage. If misfolded or damaged proteins accumulate beyond a certain critical point, neurodegenerative diseases such as Huntington's, Parkinson's, Alzheimer's and Lou Gehrig's diseases can result.
Morimoto and Morley studied C. elegans, a transparent roundworm whose biochemical environment is similar to that of human beings and whose genome, or complete genetic sequence, is known. In their experiments, the researchers found that when heat shock factor, the master gene that controls the expression of all chaperones, was underexpressed in adult animals, longevity was suppressed. When heat shock factor was overexpressed, lifespan increased. The results suggest that heat shock factor has significant beneficial effects to the organism as a whole.
"The heat shock response is identical in all life on Earth," said Morimoto, who was the first to clone a human heat shock gene in 1985.
The research was supported by the National Institute of General Medical Sciences, the National Institute of Neurological Disease and Stroke, Huntington's Disease Society of America and the Daniel F. and Ada L. Rice Foundation.
Journal
Molecular Biology of the Cell