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Vol. LXIV, No. 4
February 17, 2012
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Digest

Probable Mechanism Underlying Resveratrol Activity Found

NIH researchers and their colleagues have identified how resveratrol, a naturally occurring chemical found in red wine and other plant products, may confer its health benefits. The authors present evidence that resveratrol does not directly activate sirtuin 1, a protein associated with aging. Rather, the authors found that resveratrol inhibits certain types of proteins known as phosphodiesterases, enzymes that help regulate cell energy.

These findings may help settle the debate regarding resveratrol’s biochemistry and pave the way for resveratrol-based medicines. The chemical has received significant interest from pharmaceutical companies for its potential to combat diabetes, inflammation and cancer. The study appeared in the Feb. 3 issue of Cell.

“Resveratrol has potential as a therapy for diverse diseases such as type 2 diabetes, Alzheimer’s disease and heart disease,” said lead author Dr. Jay H. Chung, chief of the Laboratory of Obesity and Aging Research, NHLBI. “However, before researchers can transform resveratrol into a safe and effective medicine, they need to know exactly what it targets in cells.”

Gene Regulator in Brain’s Executive Hub Tracked Across Lifespan

For the first time, scientists have tracked the activity, across the lifespan, of an environmentally responsive regulatory mechanism that turns genes on and off in the brain’s executive hub. Among key findings of the study by NIH scientists: genes implicated in schizophrenia and autism turn out to be members of a select club of genes in which regulatory activity peaks during an environmentally sensitive critical period in development. The mechanism, called DNA methylation, abruptly switches from off to on within the human brain’s prefrontal cortex during this pivotal transition from fetal to postnatal life. As methylation increases, gene expression slows down after birth.

Epigenetic mechanisms like methylation leave chemical instructions that tell genes what proteins to make—what kind of tissue to produce or what functions to activate. Although not part of our DNA, these instructions are inherited from our parents. But they are also influenced by environmental factors, allowing for change throughout the lifespan.

“Developmental brain disorders may be traceable to altered methylation of genes early in life,” explained Dr. Barbara Lipska of the National Institute of Mental Health, lead author of the study. “For example, genes that code for the enzymes that carry out methylation have been implicated in schizophrenia. In the prenatal brain, these genes help to shape developing circuitry for learning, memory and other executive functions which become disturbed in the disorders. Our study reveals that methylation in a family of these genes changes dramatically during the transition from fetal to postnatal life—and that this process is influenced by methylation itself, as well as genetic variability. Regulation of these genes may be particularly sensitive to environmental influences during this critical early life period.”

Lipska and colleagues reported their work Feb. 2 online in the American Journal of Human Genetics.

Caffeine Consumption Linked to Estrogen Changes

Caffeine Consumption Linked to Estrogen Changes

Asian women who consumed an average of 200 milligrams or more of caffeine a day—the equivalent of roughly two cups of coffee—had elevated estrogen levels when compared to women who consumed less, according to a study of reproductive age women by researchers at NIH and other institutions.

However, white women who consumed 200 milligrams or more of caffeine a day had slightly lower estrogen levels than women who consumed less. Black women who consumed 200 milligrams or more of caffeine a day were found to have elevated estrogen levels, but this result was not statistically significant.

The changes in estrogen levels among the women who took part in the study did not appear to affect ovulation. Studies conducted in animals had suggested that caffeine might interfere with ovulation. The study was published online in the American Journal of Clinical Nutrition.

“The results indicate that caffeine consumption among women of child-bearing age influences estrogen levels,” said Dr. Enrique Schisterman of NICHD. “Short term, these variations in estrogen levels among different groups do not appear to have any pronounced effects. We know that variations in estrogen level are associated with such disorders as endometriosis, osteoporosis and endometrial, breast and ovarian cancers. Because long-term caffeine consumption has the potential to influence estrogen levels over a long period of time, it makes sense to take caffeine consumption into account when designing studies to understand these disorders.”


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