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Archive - 11 - 2010

Scientists Discover Molecular 'Switch' That Contributes to Cellular Aging Process

Posted by dlife on Tue, Nov 30, 10, 10:28 PM 0 Comment

November 30, 2010 (EurekAlert) - A team of Harvard School of Public Health (HSPH) scientists report finding a molecular "switch" that can "turn off" some cellular processes that are protective against aging and metabolic diseases. While more research is needed, the findings may open doors for new drug treatments to halt or slow development of metabolic diseases like type 2 diabetes or heart disease. The research findings appear in the December 1, 2010 issue of Cell Metabolism. Scientists want to better understand why some people often those who are older, overweight, or obese develop metabolic syndrome, a condition characterized by a group of risk factors, including high blood glucose, high cholesterol, insulin resistance, fatty liver, and increased abdominal fat. This condition increases the risk of heart disease, type 2 diabetes, and other diseases, including cancer. Using genetically altered mouse models, senior author Chih-Hao Lee, assistant professor of genetics and complex diseases at HSPH, first author Shannon Reilly, an HSPH graduate student, and their colleagues focused on the role of the protein SMRT (silencing mediator of retinoid and thyroid hormone receptors) in the aging process. They found aged cells accumulate more SMRT and wanted to see if SMRT increases the damaging effects of oxidative stress on mitochondria, the cell component that converts food and oxygen into energy and powers metabolic activities. Oxidative stress is a cellular process that damages DNA, protein, and other cell functions and can lead to age-related diseases such as type 2 diabetes, Alzheimer's, Parkinson's, and atherosclerosis. In laboratory experiments, Reilly, Lee, and colleagues found that in older animals SMRT acts like a "switch," turning off the protective cellular activities of proteins known as peroxisome proliferator-activated receptors (PPARs). PPARs help regulate genes that promote fat burning to maintain lipid (blood fat) balance and reduce oxidative stress. The researchers were able to reduce the negative effects of oxidative stress by giving antioxidants or drugs known to turn the protective activities of PPARs back on. The scientists knew that oxidative damage causes the body to age. What they did not know is why aged cells have more oxidative damage. "The significance of our study is that we show SMRT facilitates this process," Lee said. "In other words, the normal metabolic homeostasis is maintained, in part, by PPARs. SMRT acts as a metabolic switch to turn off PPAR activities when the cells age." PPAR drugs have been used to increase insulin sensitivity and lower blood lipid levels. "Our study shows PPARs might also be used to boost the body's ability to handle oxidative stress," Lee said. "With what we have learned, we believe SMRT is one of the key players that causes age-dependent decline in mitochondrial function by blocking PPAR activity, and we've found a way to boost the body's ability to better handle metabolic and oxidative stress," Lee said. "This finding is significant since increased oxidative stress, coupled with reduced metabolic function, contributes to the aging process and the development of age-related metabolic diseases." In collaboration with epidemiologists at HSPH, the team found genetic variations in the human SMRT gene that are associated with risk of type 2 diabetes. "Through this study we were able to validate that our findings in the animal model apply to human diseases," Lee said.

Belly Fat Puts Women at Risk for Osteoporosis

Posted by dlife on Tue, Nov 30, 10, 01:44 PM 0 Comment

November 30, 2010 (EurekAlert) - For years, it was believed that obese women were at lower risk for developing osteoporosis, and that excess body fat actually protected against bone loss. However, a study presented today at the annual meeting of the Radiological Society of North America (RSNA) found that having too much internal abdominal fat may, in fact, have a damaging effect on bone health."We know that obesity is a major public health problem," said the study's lead author, Miriam A. Bredella, M.D., a radiologist at Massachusetts General Hospital and assistant professor of radiology at Harvard Medical School in Boston. "Now we know that abdominal obesity needs to be included as a risk factor for osteoporosis and bone loss."According to the Centers for Disease Control and Prevention (CDC), approximately 72 million American adults are considered obese. The CDC defines obesity as having a body mass index (BMI) of 30 or more. Obesity is associated with many health problems including cardiovascular diseases, diabetes, high cholesterol, asthma, sleep apnea and joint diseases. Yet despite all the health issues, it was commonly accepted that women with increased body weight were at lower risk for bone loss.But not all body fat is the same. Subcutaneous fat lies just below the skin, and visceral or intra-abdominal fat is located deep under the muscle tissue in the abdominal cavity. Genetics, diet and exercise are all contributors to the level of visceral fat that is stored in the body. Excess visceral fat is considered particularly dangerous, because in previous studies it has been associated with increased risk for heart disease.Dr. Bredella and colleagues set out to evaluate the abdominal subcutaneous, visceral and total fat, as well as bone marrow fat and bone mineral density, in 50 premenopausal women with a mean BMI of 30. Each woman underwent an MR spectroscopy exam to evaluate the bone marrow fat of the L4, the fourth vertebra in the lumbar section of the spine. Then, the bone mineral density of the L4 was assessed using quantitative computed tomography (QCT), which measures bone mass and is used to assess bone loss.The imaging revealed that women with more visceral fat had increased bone marrow fat and decreased bone mineral density. However, there was no significant correlation between either subcutaneous fat or total fat and bone marrow fat or bone mineral density. "Our results showed that having a lot of belly fat is more detrimental to bone health than having more superficial fat or fat around the hips," Dr. Bredella said.According to the National Women's Health Information Center, 10 million Americans have osteoporosis and 18 million more have low bone mass, placing them at risk for the disease."It is important for the public to be aware that excess belly fat is a risk factor for bone loss, as well as heart disease and diabetes," Dr. Bredella said.While bone loss is more common in women, the research team is currently conducting a study to determine whether belly fat is also a risk factor for bone loss in men.

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