Prenatal exposure to stress linked to accelerated cell aging

ScienceDaily (Aug. 1, 2011) — Young adults whose mothers experienced psychological trauma during their pregnancies show signs of accelerated aging, a UC Irvine-led study found.

The researchers discovered that this prenatal exposure to stress affected the development of chromosome regions that control cell aging processes. The study results, which appear online this week in the Proceedings of the National Academy of Sciences, point to the importance of maternal health and well-being during pregnancy.

"Our previous research on prenatal stress exposure has shown its effects on long-term metabolic, immune, endocrine and cognitive function," said the paper's lead author, Dr. Pathik D. Wadhwa, UCI professor of psychiatry & human behavior, obstetrics & gynecology, pediatrics, and epidemiology. "But this is the first to show the impact of prenatal stress on cell aging in humans, and it sheds light on an important biological pathway underlying the developmental origins of adult disease risk."

Study participants were healthy 25-year-old women and men born to mothers who had, during pregnancy, experienced psychosocial stress in the form of major, traumatic life events, such as the death or sudden severe illness of an immediate family member. Blood tests revealed that subjects' white blood cells had aged an average of three and a half more years -- five among women -- than those of individuals whose mothers had uneventful pregnancies.

This hastened aging was evidenced by the shortened length of telomeres, repetitive stretches of DNA-protein complexes that cap and protect the ends of chromosomes. Telomeres maintain chromosomal stability and control the processes that underlie cellular aging by functioning as a "clock" that regulates how many times a cell can divide. The shorter the telomere strands, the faster the cell ages.

The telomere maintenance system plays an important role in human disease and longevity, and scientists now know that telomere length is correlated to the risk of disease and premature mortality in humans. Truncated telomeres -- such as those found in the white blood cells of study participants -- can, for example, be a precursor to diabetes, cancer and coronary heart disease.

"These results indicate that stress exposure in intrauterine life is a significant predictor of adult telomere length -- even after accounting for other established prenatal and postnatal influences on telomere length," said Sonja Entringer, UCI assistant professor of pediatrics and first author on the paper.

A rapidly emerging body of human and animal research indicates that intrauterine conditions play an important role not only in all aspects of fetal development and health across gestation and birth, but also in a wide range of physical and mental health outcomes over an individual's entire lifespan.

Elizabeth H. Blackburn, Elissa S. Epel and Jue Lin of UC San Francisco and German researchers Robert Kumsta, Dirk H. Hellhammer and Stefan Wust contributed to the study, which was supported by the National Institutes of Health and the Barney & Barbro Fund.

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The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of California - Irvine, via EurekAlert!, a service of AAAS.

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How memory is lost: Loss of memory due to aging may be reversible

ScienceDaily (July 28, 2011) — Yale University researchers can't tell you where you left your car keys -- but they can tell you why you can't find them.

A new study published July 27 in the journal Nature shows the neural networks in the brains of the middle-aged and elderly have weaker connections and fire less robustly than in youthful ones. Intriguingly, the research suggests that this condition is reversible.

"Age-related cognitive deficits can have a serious impact on our lives in the Information Age as people often need higher cognitive functions to meet even basic needs, such as paying bills or accessing medical care," said Amy Arnsten, Professor of Neurobiology and Psychology and a member of the Kavli Institute for Neuroscience. "These abilities are critical for maintaining demanding careers and being able to live independently as we grow older."

As people age, they tend to forget things more often, are more easily distracted and disrupted by interference, and have greater difficulty with executive functions. While these age-related deficits have been known for many years, the cellular basis for these common cognitive difficulties has not been understood. The new study examined for the first time age-related changes in the activity of neurons in the prefrontal cortex (PFC), the area of the brain that is responsible for higher cognitive and executive functions.

Networks of neurons in the prefrontal cortex generate persistent firing to keep information "in mind" even in the absence of cues from the environment. This process is called "working memory," and it allows us to recall information, such as where the car keys were left, even when that information must be constantly updated. This ability is the basis for abstract thought and reasoning, and is often called the "Mental Sketch Pad." It is also essential for executive functions, such as multi-tasking, organizing, and inhibiting inappropriate thoughts and actions.

Arnsten and her team studied the firing of prefrontal cortical neurons in young, middle-aged and aged animals as they performed a working memory task. Neurons in the prefrontal cortex of the young animals were able to maintain firing at a high rate during working memory, while neurons in older animals showed slower firing rates. However, when the researchers adjusted the neurochemical environment around the neurons to be more similar to that of a younger subject, the neuronal firing rates were restored to more youthful levels.

Arnsten said that the aging prefrontal cortex appears to accumulate excessive levels of a signaling molecule called cAMP, which can open ion channels and weaken prefrontal neuronal firing. Agents that either inhibited cAMP or blocked cAMP-sensitive ion channels were able to restore more youthful firing patterns in the aged neurons. One of the compounds that enhanced neuronal firing was guanfacine, a medication that is already approved for treating hypertension in adults, and prefrontal deficits in children, suggesting that it may be helpful in the elderly as well.

Arnsten's finding is already moving to the clinical setting. Yale is enrolling subjects in a clinical trial testing guanfacine's ability to improve working memory and executive functions in elderly subjects who do not have Alzheimer's Disease or other dementias.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Yale University.

Journal Reference:

Min Wang, Nao J. Gamo, Yang Yang, Lu E. Jin, Xiao-Jing Wang, Mark Laubach, James A. Mazer, Daeyeol Lee, Amy F. T. Arnsten. Neuronal basis of age-related working memory decline. Nature, 2011; DOI: 10.1038/nature10243

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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