Hidden from sight, our cells battle challenges such as their environment, bacteria, viruses, too much or too little oxygen, and physiological stressors. Molecular systems protect cells under assault, but those systems can break down, especially with age.

To better understand how cells are protected from stress and damage, a team led by Northwestern University researchers studied the effect of resveratrol, a beneficial chemical found in red wine, on human cells in tissue culture.

The findings may help explain what happens in neurodegenerative diseases, which are age-related, when cell protection fails, proteins misfold, lots of damage accumulates and the system falls apart.

The researchers discovered a new molecular relationship critical to keeping cells healthy across a long span of time: a protein called SIRT1, important for caloric restriction and lifespan and activated by resveratrol, regulates heat shock factor 1 (HSF1), keeping it active. HSF1 in turn senses the presence of damaged proteins in the cell and elevates the expression of molecular chaperones to keep a cell’s proteins in a folded, functional state. Regulation of this pathway has a direct beneficial effect to cells, the research shows.

This role of SIRT1 — a protein already of great interest to pharmaceutical companies — was not previously known. The results will be published in the Feb. 20 issue of the journal Science.

“When SIRT1 levels are high, you are in a high-protection mode,” said Richard I. Morimoto, Bill and Gayle Cook Professor of Biochemistry, Molecular Biology and Cell Biology in Northwestern’s Weinberg College of Arts and Sciences. He led the research team.

“Ironically, triggering the stress response and perhaps maintaining the cell in a protective state over a long period of time can keep cells healthy,” said Morimoto. “The cell is protected against an accumulation of damage when HSF1 is more active.”

SIRT1 levels decrease as humans age, Morimoto explains. Cells can’t respond to stress as well. This decrease in SIRT1 may help explain why protein misfolding diseases, such as Alzheimer’s, Parkinson’s, Huntington’s and adult-onset diabetes, are diseases of aging.

“We now have a powerful way to think about addressing neurodegenerative diseases,” said Morimoto. “We have identified a pathway that can be manipulated to alter lifespan. Discovering this new basis for therapeutics is very exciting.”

The study found that among Medicare enrollees, the prevalence of total knee replacements increased by 58 percent overall. Despite the substantial increase in the rates of total knee replacements for both populations, total knee replacements among blacks was 37 percent lower than for whites in 2000, and remained virtually unchanged in 2006. In addition, the rates for total knee replacements were lowest among black men and highest among white women.

The Importance of Taking Action

According to the Arthritis Foundation, most Americans are unaware of the seriousness of arthritis and the impact it can have on their lives. Arthritis is the nation’s most common cause of disability and costs the U.S. economy more than $128 billion annually. Knee osteoarthritis, the most frequent form of lower extremity arthritis, contributes to 418,000 knee replacement procedures annually and in 2006 accounted for 496,000 hospital discharges and $19 billion in hospital costs.

“Nearly one in two adults may develop knee osteoarthritis over their lifetime, with an equal risk among blacks and whites,” said Patience White, MD, MA, chief public health officer for the Arthritis Foundation. “There are steps Americans can take now to prevent increasing disability from knee osteoarthritis and, if surgery becomes necessary, to better prepare themselves.”

Tips for Reducing Knee Pain

To reduce the pain and disability of arthritis, the Arthritis Foundation recommends the following:

* Understand the myth about physical activity and arthritis. Many people think that physical activity can worsen arthritis pain. Nothing could be farther from the truth. Done appropriately, physical activity can help decrease symptoms of knee osteoarthritis. In addition, physical activity is an important component of weight control and helps maintain healthy bones, muscles and joints. For joint-safe exercise programs, try the Arthritis Foundation’s Life Improvement Series land or water exercise programs offered at more than 1,700 locations nationwide.

* Control weight. For those already living with symptoms, losing 15 pounds can cut knee pain in half. Maintaining a healthy weight also can lower a person’s risk of osteoarthritis. In fact, one study showed that women who lost as little as 11 pounds halved their risk of developing knee osteoarthritis and its accompanying joint pain.1

* Discover techniques to manage your arthritis. Participate in the Arthritis Foundation Self-Help Program, a self-management course that teaches people with arthritis how to manage the pain and challenges that arthritis imposes. The course has been shown to lead to a 40 percent reduction in pain.

* Learn more. Contact your local local Arthritis Foundation office or visit www.arthritis.org to learn about programs offered in your area and to order free educational materials, including literature on arthritis in African Americans. For more actions you can take, visit take control of osteoarthritis (http://www.arthritis.org/prevent-osteoarthritis.php) to get started.

About the Arthritis Foundation

The Arthritis Foundation is the leading health organization addressing the needs of some 46 million Americans living with arthritis, the nation’s most common cause of disability. Founded in 1948, with headquarters in Atlanta, the Arthritis Foundation has multiple service points located throughout the country.

The Arthritis Foundation is the largest private, not-for-profit contributor to arthritis research in the world, funding more than $400 million in research grants since 1948. The foundation helps individuals take control of arthritis by providing public health education; pursuing public policy and legislation; and conducting evidence-based programs to improve the quality of life for those living with arthritis.

“I think we’re going to see an explosion in the next five years involving the dissection of these signaling pathways whose imbalance leads to Alzheimer’s disease,” said Buck Institute Faculty Member Dale Bredesen, MD, who led the California half of the French-Californian collaborative research. “We now believe that APP is part of a ‘plasticity module’ that functions in normal memory and forgetting, and that netrin-1 gives us an important starting point to restore the normal balance.”

“We believe that Alzheimer’s disease is somewhat analogous to cancer, which results from an imbalance between the normal processes that support cell survival and those that cause cell turnover,” said Patrick Mehlen, PhD, Director of the Apoptosis, Cancer and Development CNRS Laboratory at the University of Lyon and co-senior author of the study. “Our hope is that this research will lead to therapeutics that will be used to address this imbalance much earlier in the disease process.”

Research is underway to develop a drug based on the findings. The Buck Institute and the CNRS in Lyon are partnering with Neurobiological Technologies Inc., (NASDAQ: NTII) to bring the discovery from the laboratory to clinical trials.