New insights into how cells cope with stress could help combat neurological diseases and reduce the ravages of aging. Scientists have known for years that moderate stressors, such as a calorie-restricted diet, increase lifespan in a variety of organisms. Now new research is illuminating how this works at the molecular level. A particular protein is key in regulating at least one aspect of the stress response and may be a good model for anti-aging drugs. "What we have here is an essential protective pathway that now looks like a very effective therapeutic target," said biologist Richard Morimoto of Northwestern University. Most research on this protein, called sirtuin1 (SIRT1), has concentrated on its ability to regulate and protect mitochondria — cellular power generators that are corroded over time by reactive oxygen molecules. But SIRT1 also protects DNA in the cell nucleus. Morimoto’s findings, published Thursday in Science, give a precise mechanical explanation for the effects. Cells have evolved a particular response to stay alive in adverse conditions. When a cell starts getting too hot, too hungry or too oxygen-deprived, certain proteins migrate into the nucleus. There, they latch onto sections of DNA and cause heat-shock proteins to be produced. Heatshock proteins — so named because they were first discovered in cells experiencing high temperatures — cruise around the cell, fixing damaged or improperly folded proteins. "Proteins are very delicate," Morimoto said. "Any change in the environment causes them to misfold." Repairing proteins keeps cells, and the body, in top shape. Animals exposed to only minor stresses — such as a calorie-restricted diet — reap the benefits and live longer. "A little stress is good," said lead author Sandy Westerheide, also of Northwestern. "You don’t want to overdo it, though." Normally the repair process falls off quickly,