However, clinical studies demonstrate a correlation between the presence of amyloid plaques in the brain and the severity of cognitive decline. It would seem that these amyloid plaques are found in the brains of young adults.

Few assessments of the effect of age on cognitive decline use data that spans over several years. This was the specific objective of the study led by researchers from Inserm and the University College London.

As part of the Whitehall II cohort study, medical data was extracted for 5,198 men and 2,192 women, aged between 45 and 70 at the beginning of the study, monitored over a 10-year period. The cognitive functions of the participants were evaluated three times over this time. Individual tests were used to assess memory, vocabulary, reasoning and verbal fluency.

The results show that cognitive performance (apart from the vocabulary tests) declines with age and more rapidly so as the individual’s age increases. The decline is significant in each age group.

For example, during the period studied, reasoning scores decreased by 3.6 % for men aged between 45 and 49, and 9.6 % for those aged between 65 and 70. The corresponding figures for women stood at 3.6% and 7.4% respectively.

The authors underline that evidence pointing to cognitive decline before the age of 60 has significant consequences.

“Determining the age at which cognitive decline begins is important since behavioural or pharmacological interventions designed to change cognitive aging trajectories are likely to be more effective if they are applied from the onset of decline.” underlines Archana Singh-Manoux.

“As life expectancy continues to increase, understanding the correlation between cognitive decline and age is one of the challenges of the 21st Century” she adds.

This research is part of the Whitehall II cohort study and focused on more that 7,000 people over a ten-year period.

Sources

Timing of onset of cognitive decline: results from Whitehall II prospective cohort study
Archana Singh-Manoux research director 1 2 3, Mika Kivimaki professor of social epidemiology 2, M Maria Glymour assistant professor 4, Alexis Elbaz research director 5 6, Claudine Berr research director7 8, Klaus P Ebmeier professor of old age psychiatry9, Jane E Ferrie senior research fellow10, AlineDugravot statistician 1
1Institut National de la Santé et de la Recherche Médicale (INSERM), U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, 94807 Villejuif Cedex, France;
2Department of Epidemiology and Public Health, University College London, London, UK;
3Centre de Gérontologie, Hôpital Ste Périne, AP-HP, France;
4Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA, USA;
5Institut National de la Santé et de la Recherche Médicale (INSERM), U708, F-75013, Paris, France;
6UPMC Univ Paris 06, UMR_S 708, F-75005, Paris;
7Institut National de la Santé et de la Recherche Médicale (INSERM) U1061 Université Montpellier 1, Montpellier,France;
8CMRR Languedoc-Roussillon, CHU Montpellier;
9Oxford University Department of Psychiatry, Warneford Hospital, Oxford, UK;
10University of Bristol, Bristol, UK
BMJ janvier 2012

Contact chercheur
Archana Singh Manoux
Email : Archana.Singh-Manoux@inserm.fr

Contact: Inserm Press Office
presse@inserm.fr
INSERM (Institut national de la santé et de la recherche médicale)

The vaccine was partially effective at preventing herpes simplex virus type 1 (HSV-1), but did not protect women from herpes simplex virus type 2 (HSV-2). There were less than half of the cases of genital herpes caused by HSV-1 – 58 percent fewer — in women who received the investigational vaccine compared to women who received the control vaccine.

“There is some very good news in our findings. We were partially successful against half of the equation – protecting women from genital disease caused by HSV-1,” said Robert Belshe, M.D., director of the Saint Louis University Center for Vaccine Development and lead author of the study.

“It’s a big step along the path to creating an effective vaccine that protects against genital disease caused by herpes infection. It points us in the direction to work toward making a vaccine that works on both herpes simplex viruses.”

Both HSV-1 and HSV-2 are members of the herpesvirus family. Typically, HSV-2 causes lesions and blisters in the genital area. HSV-1 generally causes sores in the mouth and lips, although it increasingly has been found to cause genital disease.

There currently is no cure or approved vaccine to prevent genital herpes infection, which affects about 25 percent of women in the United States and is one of the most common communicable diseases. Once inside the body, HSV remains there permanently. The virus can cause severe neurological disease and even death in infants born to women who are infected with HSV and the virus is a risk factor for sexual transmission of HIV.

The clinical trial of an investigational genital herpes vaccine was funded by the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health, along with GlaxoSmithKline (GSK), and conducted at 50 sites in the U.S. and Canada.

The study enrolled 8,323 women between ages 18 and 30 who did not have HSV-1 or HSV-2 infection at the start of the study. They were randomly assigned to receive either three doses of the investigational HSV vaccine that was developed by GSK or a hepatitis A vaccine, which was the control.

Participants were followed for 20 months and evaluated carefully for occurrence of genital herpes disease. In addition, all study participants were given blood tests to determine if asymptomatic infection with HSV-1 or HSV-2 occurred during the trial. Researchers found that two or three doses of the investigational vaccine offered significant protection against genital herpes disease caused by HSV-1. However the vaccine did not protect women from genital disease caused by HSV-2.

“We were surprised by these findings,” said Belshe, who also is a professor of infectious diseases and immunology at Saint Louis University School of Medicine. “We didn’t expect the herpes vaccine to protect against one type of herpes simplex virus and not another. We also found it surprising that HSV-1 was a more common cause of genital disease than was HSV-2.”

HSV-1 infection has become an increasingly common cause of genital disease, likely because more couples are engaging in oral sex. HSV-1 and HSV-2 are spread by direct contact – mouth to mouth, mouth to genitals and genitals to genitals – even when the infected person shows no symptoms, Belshe added.

Researchers are conducting laboratory tests on serum obtained from study participants as they continue to study why the vaccine protected women from genital disease caused by HSV-1 and not HSV-2.

One hypothesis, Belshe said, is HSV-1 is more easily killed by antibodies than is HSV-2. This means that the vaccine antibodies might work better against HSV-1 and result in protection from HSV-1 but not HSV-2.

Earlier studies of the investigational herpes vaccines showed it protected against genital herpes disease in women who were not infected with HSV-1 or HSV-2, but whose sexual partners were known to have genital herpes. Researchers believe the reason for the different outcome in the most recent clinical trial could be related to the fact that different populations were studied. The women in the earlier studies may have been protected due to immunologic or behavioral factors not present in the later study.

“It’s always important to confirm scientific findings in repeated studies, which is why we investigated the vaccine in a large, placebo controlled trial,” Belshe said. “Our findings confirmed the validity of the scientific process. You’ve got to have good scientific evidence that something actually works.”

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, infectious disease, liver disease, aging and brain disease and heart/lung disease.

Contact: Nancy Solomon
solomonn@slu.edu
314-977-8017
Saint Louis University

In other words, that so-called serum response factor (Srf) translates the mechanical signal of work into a chemical one.

“This signal from the muscle fiber controls stem cell behavior and participation in muscle growth,” says Athanassia Sotiropoulos of Inserm in France. “It is unexpected and quite interesting.” It might also lead to new ways to combat muscle atrophy.

Sotiropoulos’ team became interested in Srf’s role in muscle in part because their earlier studies in mice and humans showed that Srf concentrations decline with age. That led them to think Srf might be a culprit in the muscle atrophy so common in aging.

The new findings support that view, but Srf doesn’t work in the way the researchers had anticipated. Srf was known to control many other genes within muscle fibers. That Srf also influences the activities of the satellite stem cells came as a surprise.

Mice with muscle fibers lacking Srf are no longer able to grow when they are experimentally overloaded, the new research shows. That’s because satellite cells don’t get the message to proliferate and fuse with those pre-existing myofibers.

Srf works through a network of genes, including one known as Cox2. That raises the intriguing possibility that commonly used Cox2 inhibitors – think ibuprofen – might work against muscle growth or recovery, Sotiropoulos notes.

Treatments designed to tweak this network of factors might be used to wake muscle stem cells up and enhance muscle growth in circumstances such as aging or following long periods of bed rest, she says. Most likely, such therapies would be more successfully directed not at Srf itself, which has varied roles, but at its targets.

“It may be difficult to find a beneficial amount of Srf,” she says. “Its targets, interleukins and prostaglandins, may be easier to manipulate.”

Contact: Elisabeth (Lisa) Lyons
elyons@cell.com
617-386-2121
Cell Press

“For too long, patients and families have suffered from debilitating, incurable diseases and we know that stem cell research offers hope to millions of Americans across the country. I am committed to supporting responsible stem cell research now, and in the future,” said President Obama in his response to the questionnaire.

“I strongly support adult stem cell research,” said Gingrich. “I will oppose at every turn any process of destroying embryos.”

In the area of global competitiveness, Gingrich said, “Considering today’s American tax and regulatory systems, it is increasingly likely that the full implementation of the new [scientific] knowledge will first occur outside the United States and be imported by us. This will be tragic for Americans in lost health opportunities, lost jobs and prosperity, and unnecessarily higher healthcare costs.”

“To compete for the jobs and industries of our time, we have to make America the best place on earth to do business and out-innovate, out-educate, and out-build the rest of the world,” said Obama. “I have called for a level of research and development we haven’t seen since the height of the Space Race and sent budgets to Congress that helps us meet that goal.”

Obama and Gingrich also responded to questions about support for the National Institutes of Health, the Centers for Disease Control and Prevention, the Food and Drug Administration, science, technology, engineering and math education, and government investment in health research for military veterans. www.yourcandidatesyourhealth.org. All presidential candidates were invited to participate.

The responses from Obama and Gingrich largely reflect public sentiment on federal support for research. In new public opinion poll data, a vast majority of Americans (86%) believe investing in health research is important for job creation and economic recovery and (54%) say research is part of the solution to rising health care costs. Seventy-seven percent believe the U.S. is losing its global competitive edge in science and innovation. However, 60% say they are uninformed about their representatives’ positions on medical, health and scientific research.

“Unfortunately, many elected officials and candidates have failed to elevate these issues in their campaigns,” said Mary Woolley, president and CEO of Research!America. “The poll underscores Americans’ willingness to make research a high priority to address our economic and health challenges.”

In other polling data, most Americans say it’s important to increase funding for federal health research agencies — (86%) for the Centers for Disease Control and Prevention (CDC), (79%) for the Food and Drug Administration (FDA) and (75%) for the National Institutes of Health (NIH).

“Americans realize that massive spending cuts for federal agencies like the NIH would move our country in the wrong direction,” said Research!America’s chair, former Illinois Congressman John Porter. “A strong investment in research will yield more scientific discoveries, boost our global competitiveness and help lower health care costs. We need elected officials who will aggressively support and expand research and development.”

Additional findings from the public opinion poll include:

• 85% think research and innovation is important to their state economy.
• 48% say there is not enough government investment in health research for the benefit of military veterans and service members.
• 82% say it’s important to conduct medical or health research to eliminate health disparities.
• 73% believe the federal government should place more emphasis on increasing the number of young Americans who pursue careers in science, technology, engineering and mathematics.
• 61% favor expanding federal funding for research using embryonic stem cells.

About the Poll: Research!America commissioned JZ Analytics to conduct an online survey of 800 adults nationwide in October 2011. The sample is representative of the nation’s demographics, including geography, gender and ethnicity, with a theoretical error of ±3.0%. The full results can be found at http://www.researchamerica.org/uploads/December2011PollRelease.pdf

For more information about Your Candidates – Your Health, visit www.yourcandidatesyourhealth.org. Supporting partners include the American Heart Association, American Cancer Society Cancer Action Network, Alzheimer’s Association, Pfizer, American Association of Colleges of Pharmacy, American Association for Dental Research, Assurant, Brain & Behavior Research Foundation, Charles Drew University, Cold Spring Harbor Laboratory, Food Allergy Initiative, Howard Hughes Medical Institute, Leukemia & Lymphoma Society, Lovelace, National Alliance for Eye and Vision Research, National Alliance for Hispanic Health, New York-Presbyterian, Northeast Ohio Medical University, Society for Neuroscience, University of Michigan, University of North Carolina School of Medicine and Washington University School of Medicine.

About Us: Research!America is the nation’s largest not-for-profit public education and advocacy alliance working to make research to improve health a higher national priority. Founded in 1989, Research!America is supported by member organizations representing 125 million Americans. Visit www.researchamerica.org.

Contact: Suzanne Ffolkes
sffolkes@researchamerica.org
571-482-2710
Research!America

A study of 26 wealthy nations shows that countries with a higher density of fast food restaurants per capita had much higher obesity rates compared to countries with a lower density of fast food restaurants per capita.

“It’s not by chance that countries with the highest obesity rates and fast food restaurants are those in the forefront of market liberalization, such as the United States, the United Kingdom, Australia, New Zealand and Canada, versus countries like Japan and Norway, with more regulated and restrictive trade policies,” said Roberto De Vogli, associate professor in the U-M School of Public Health, and lead researcher of the study.

For example, in the United States, researchers reported 7.52 fast food restaurants per 100,000 people, and in Canada they reported 7.43 fast food restaurants per 100,000 people. The paper reported the obesity rates among US men and women were 31.3 percent and 33.2 percent, respectively. The obesity rates for Canadian men and women were 23.2 percent and 22.9 percent, respectively.

Compare that to Japan, with 0.13 fast food restaurants per 100,000 people, and Norway, with 0.19 restaurants per capita. Obesity rates for men and women in Japan were 2.9 percent and 3.3 percent, respectively. In Norway, obesity rates for men and women were 6.4 percent and 5.9 percent, respectively. The relationships remain consistent even when researchers controlled for variables such as income, income inequality, urban areas, motor vehicles and internet use per capita.

Obesity research largely overlooks the global market forces behind the epidemic, De Vogli said.

“In my opinion the public debate is too much focused on individual genetics and other individual factors, and overlooks the global forces in society that are shaping behaviors worldwide. If you look at trends overtime for obesity, it’s shocking,” De Vogli said.

“Since the 1980s, since the advent of trade liberalization policies that have indirectly…promoted transnational food companies…we see rates that have tripled or quadrupled. There is no biological, genetic, psychological or community level factor that can explain this. Only a global type of change can explain this.”

Researchers chose one fast food restaurant to use as a proxy measure for how many fast food restaurants were present per 100,000. The study is in no way an indictment of that restaurant, De Vogli said, but rather an indicator of fast food density in a particular area.

Fast food refers to food sold in restaurants or stores with preheated or precooked ingredients, and served to the customer in a packaged form. A typical fast food meal includes a hamburger, fries and a soft drink, the paper said. Fast food is usually high in fat and calories, and several studies have found associations between fast food intake and increased body mass index, weight gain and obesity. Obesity accounts for approximately 400,000 deaths each year in the United States alone. Fast food consumption is also related to insulin resistance and type II diabetes, another major worldwide public health threat.

The paper, “Globesization: ecological evidence on the relationship between fast food outlets and obesity among 26 advanced economies,” will be published in the December print issue of Critical Public Health. The study was funded by a grant from the Economic and Social Research Council.

For more on De Vogli: http://www.sph.umich.edu/iscr/faculty/profile.cfm?uniqname=rdevogli.

The University of Michigan School of Public Health has been promoting health and preventing disease since 1941, and is ranked among the top public health schools in the nation. Whether making new discoveries in the lab or researching and educating in the field, our faculty, students, and alumni are deployed around the globe to promote and protect our health. http://www.sph.umich.edu/

Contact: Laura Bailey
baileylm@umich.edu
734-764-1552
University of Michigan

Youths treated at hospital emergency rooms for suicidal behavior remain at very high risk for future suicide attempts. But despite the urgent need to provide them with mental health follow-up care, many don’t receive any such care after their discharge. Consequently, a major goal of the U.S. Department of Health and Human Service’s National Strategy for Suicide Prevention has been to increase rates of follow-up care after discharge for patients who come to the emergency department (ED) due to suicidal behavior.

Now, a new study by UCLA researchers shows that a specialized mental health intervention for suicidal youth can help. Reporting in the November issue of the journal Psychiatric Services, Joan Asarnow, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA, and colleagues show that a family-based intervention conducted while troubled youths were still being treated in the ED led to dramatic improvements in linking these youths to outpatient treatment following their discharge.

“Youths who are treated for suicidal behavior in emergency departments are at very high risk for future attempts,” said Asarnow, the study’s first author. “Because a large proportion of youths seen in the ED for suicide don’t receive outpatient treatment after discharge, the United States National Strategy for Suicide Prevention identifies the ED as an important suicide prevention site. So, a national objective is to increase the rates of mental health follow-up treatment for suicidal patients coming out of EDs.”

But how to encourage this with youths when they are at their most vulnerable? The study involved 181 suicidal youths at two EDs in Los Angeles County, with a mean age of 15. Sixty-nine percent were female, and 67 percent were from racial or ethnic minority groups. For 53 percent of the participants, their emergency department visit was due to a suicide attempt. The remainder were seen because they had thoughts of suicide.

The youths were randomly assigned to either the usual ED treatment or an enhanced mental health intervention that involved a family-based crisis-therapy session designed to increase motivation for outpatient follow-up treatment and improve the youths’ safety, supplemented by telephone contacts aimed at supporting families in linking to further outpatient treatment.

The results of the study show that the enhanced mental health intervention was associated with higher rates of follow-up treatment. Of the participants in the enhanced intervention, 92 percent received follow-up treatment after discharge, compared with 76 percent in the standard ED treatment arm – a clinically significant difference.

While the results are positive, the study is only a first step, according to Asarnow, who also directs UCLA’s Youth Stress and Mood Program.

“The results underscore the urgent need for improved community outpatient treatment for suicidal youths,” she said. “Unfortunately, the follow-up data collected at about two months after discharge did not indicate clinical or functioning differences among youths who received community outpatient treatment and those who did not.”

Still, Asarnow said, the data from the new study underscores the critical importance of this work. To address the need for effective follow-up treatment for troubled youths, the UCLA Youth Stress and Mood Program has major research trials in progress aimed at evaluating outpatient treatments for preventing suicide and suicide attempts.

Funding for the study was provided by the Centers for Disease Control and Prevention, the National Institute of Mental Health and the American Foundation for Suicide Prevention.

Other authors included Larry Baraff, Robert Suddath, John Piacentini, Mary Jane Rotheram-Borus and Lingqi Tang, all of UCLA; Michele Berk and Charles Grob of Harbor – UCLA Medical Center, Los Angeles Biomedical Research Institute; Mona Devich-Navarro of Santa Monica College; and Daniel Cohen of Johns Hopkins University.

Asarnow reports receiving honoraria from Hathaways-Sycamores, Casa Pacifica, the California Institute of Mental Health and the Melissa Institute. Piacentini has received royalties from Oxford University Press for treatment manuals and from Guilford Press and the American Psychological Association Press for books on child mental health. In addition, he has received a consultancy fee from Bayer Schering Pharma. The other authors report no competing interests.

The UCLA Department of Psychiatry and Biobehavioral Sciences is the home within the David Geffen School of Medicine at UCLA for faculty who are experts in the origins and treatment of disorders of complex human behavior. The department is part of the Semel Institute for Neuroscience and Human Behavior at UCLA, a world-leading interdisciplinary research and education institute devoted to the understanding of complex human behavior and the causes and consequences of neuropsychiatric disorders.

For more news, visit the UCLA Newsroom and follow us on Twitter.

Contact: Mark Wheeler
mwheeler@mednet.ucla.edu
310-794-2265
University of California – Los Angeles

Medicaid, which is jointly funded by the federal and state governments, covers the health care costs of eligible low-income individuals and families. The Affordable Care Act of 2010 expands Medicaid to cover additional low-income adults in all states by 2014.

“The lower estimate of Medicaid enrollees suggests that the ACA will not be as successful as envisioned in insuring low-income Americans; the high-end estimate implies that the federal cost of expanding Medicaid eligibility will be a good deal higher than expected and accounted for,” said Arnold Epstein, John H. Foster Professor of Health Policy and Management and chair, Department of Health Policy and Management at HSPH and the study’s senior author.

The study was published online October 26, 2011, and will appear in the November print edition of Health Affairs.

The HSPH researchers, including lead author Benjamin Sommers, assistant professor of health policy and economics, and Katherine Swartz, professor of health economics and policy, created a simulation model to determine the range of reasonable projections, estimating eligibility, participation, and population growth using prior research and other data.

The researchers’ model predicts that the number of people enrolling in Medicaid under health reform may vary by more than 10 million, with a “best-guess” estimate of 13.4 million, and a possible range of 8.5 million to 22.4 million. Their model estimates that annual federal spending for new Medicaid enrollees will range from $34 billion to $98 billion in 2019, and that 4,500 to 12,100 new physicians will be needed to care for new enrollees.

Prior research shows that a decreasing number of doctors are willing to treat new Medicaid patients, due to low reimbursement rates. This suggests that policymakers will need to take additional steps to ensure that there are enough providers to care for new Medicaid enrollees.

Last year, Medicaid covered nearly 69 million Americans, at an annual cost of over $400 billion. This means that even with the highest-cost estimate of $98 billion, Sommers and colleagues project that the Medicaid expansion under the ACA will represent less than one-quarter of total spending in the program.

“In the end, Medicaid enrollment will be determined largely by the extent to which federal and state efforts encourage or discourage eligible people from enrolling,” Swartz said. “The budget scoring rules require CBO to produce one cost number but that number is an estimate. Policymakers are better served if they have the range of cost estimates so possible higher costs are anticipated.”

Support for the study was provided in part by the Agency for Healthcare Research and Quality.

“Policy Makers Should Prepare for Major Uncertainties in Medicaid Enrollment, Costs, and Needs for Physicians Under Health Reform,” Benjamin Sommers, Katherine Swartz, and Arnold Epstein, Health Affairs, November, 2011.

Visit the HSPH website for the latest news, press releases and multimedia offerings.

Harvard School of Public Health (http://www.hsph.harvard.edu) is dedicated to advancing the public’s health through learning, discovery, and communication. More than 400 faculty members are engaged in teaching and training the 1,000-plus student body in a broad spectrum of disciplines crucial to the health and well being of individuals and populations around the world. Programs and projects range from the molecular biology of AIDS vaccines to the epidemiology of cancer; from risk analysis to violence prevention; from maternal and children’s health to quality of care measurement; from health care management to international health and human rights. For more information on the school visit: http://www.hsph.harvard.edu

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“More than a quarter of people in mortgage default or foreclosure are over 50,” says the study’s principal investigator, Dawn E. Alley, PhD, assistant professor of epidemiology and public health at the University of Maryland School of Medicine. “For an older person with chronic conditions like diabetes or hypertension, the types of health problems we saw are short term consequences of falling behind on a mortgage that could have long-run implications for that person’s health.”

The study was prompted in part by the rapid rise in foreclosure rates that began in 2007 following a dramatic increase in subprime lending. By 2009, 2.21 percent of all homes in the United States, a total of more than 2.8 million properties, were in some stage of foreclosure. Previous research had shown that home ownership is associated with better health while financial strain is associated with worse health and higher death rates.

“This study has pinpointed an issue that until now has been somewhat under the radar, but which threatens to become a major public health crisis if not addressed,” says E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and dean of the University of Maryland School of Medicine. “Through research such as this, faculty epidemiologists and public health specialists provide valuable information and perspectives that are useful for government and private policy makers as they work to meet the health and economic needs of Americans.”

The researchers examined data from the Health and Retirement Study, a nationally representative panel study of Americans older than age 50. In 2008, 2,474 participants were asked if they had fallen more than two months behind on mortgage payments since 2006. The survey included questions designed to measure psychological impairment, general health status and access to important health-relevant resources. In predicting these health outcomes, researchers controlled for demographic factors, health behaviors, chronic diseases, sources of debt and annual household income.

Among participants who were mortgage delinquent, 22 percent developed elevated depressive symptoms over the two-year period compared to only three percent of non-delinquent respondents. Twenty-eight percent of mortgage-delinquent participants reported food insecurity compared to four percent in the non-delinquent group. In addition, the delinquent group reported much higher levels of cost-related medication non-adherence (32 percent compared to five percent).

The study also found that lower-income and minority homeowners were at higher risk for mortgage default. “Our results suggest that the housing crisis may be making health disparities worse,” says Dr. Alley, “because these groups had poorer health, lower incomes and higher levels of debt even before the current mortgage crisis.” The researchers note that it will likely take decades for African American and Hispanic communities to recover the wealth lost during the housing crisis and that minority communities are disproportionately affected by declining home values and lost tax revenue.

The study began just as mortgage delinquencies and subsequent home foreclosures began to rise in the United States, driven mainly by increases in mortgage payments related to adjustable rate loans. Dr. Alley says the health picture is much worse today because rising mortgage defaults are compounded by unemployment. “Recent data from the Centers for Disease Control and Prevention show that the number of Americans with depression has been increasing along with rising unemployment.”

Dr. Alley adds that mortgage counselors are seeing a rising tide of health issues. “We did a separate nationwide survey of mortgage counselors and found that almost 70 percent of them said many of the clients they worked with were depressed or hopeless. About a third of them said they had worked with someone in the last month who expressed intent for self harm or suicide. These are very serious and clearly ongoing issues.”

This study was supported by the National Institutes of Health. It was conducted with support, resources and use of facilities from the Philadelphia Veterans Affairs Medical Center in conjunction with the Organized Research Center on Aging at the University of Maryland School of Medicine.

Alley DE, Lloyd J, Pagan JA, Pollack CE, Shardell M, Cannuscio C. “Mortgage delinquency and changes in access to health resources and depressive symptoms in a nationally representative cohort of Americans older than 50 years.” American Journal of Public Health. Published online October 20, 2011. doi: 10.2105/AJPH.2011. 300245

Contact: Bill Seiler
bseiler@umm.edu
410-328-8919
University of Maryland Medical Center

The new study, published Oct. 17 in Cancer Cell, identifies the protein SIRT2 as a tumor suppressor linked to gender-specific tumor development in mice. Along with two other “sirtuin” proteins previously linked to cancer, the new finding suggests the existence of a rare “family” of tumor suppressors.

Cancer is primarily a disease of aging, with the majority of cancer cases occurring in people over 50. However, the biological processes that underlie this association are not clear.

In the late-1990s, sirtuins were linked to extended lifespan observed in several species maintained on a calorically restricted diet. These nutrient-sensing proteins seemed to defend against aging-related cellular damage.

“The single most important prognostic factor in cancer is increasing age,” said Gius, a professor of Radiation Oncology and associate professor of Cancer Biology at Vanderbilt-Ingram. “It seems logical that the genes that play a role in aging – or perhaps better stated, anti-aging – would be connected to cancer.”

While at the NIH’s National Cancer Institute, Gius and colleagues found that when they eliminated SIRT3 – a sirtuin localized in the mitochondria, the cellular “power plants” – the mice developed ER/PR positive breast tumors, the most common type of breast cancer in postmenopausal women.

In the new study, Gius’ lab – working with senior author Chu-Xia Deng, Ph.D., and colleagues at the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases – investigated the physiological functions of SIRT2 by eliminating the protein in cultured cells and in mice.

They found that SIRT2-deficient mice developed tumors in multiple tissues – and, strangely, male mice and female mice developed tumors in different tissues. Lack of SIRT2 in female mice led to mammary (breast) tumors, while male mice lacking SIRT2 developed a range of gastrointestinal tumors (in the liver, pancreas, colon and stomach).

“It’s kind of a startling observation, that you’d knock a protein out, and you’d get gender-specific tumors, suggesting a physiological connection between gender and the function of sirtuin proteins” Gius said.

From human cancer data, the investigators showed that SIRT2 was also decreased in human cases of breast cancer, gastrointestinal tumors (which were not broken down by gender), and several other cancer types.

While the mechanism underlying the gender-specific tumors was not determined, the researchers did find evidence that SIRT2 acted as a tumor suppressor in cultured cells. Specifically, the protein appeared to regulate an important part of the machinery involved in cell division – a protein complex called APC/C. Loss of SIRT2 led to “genomic instability,” or an abnormal segregation of chromosomes during cell division. While the cells at first showed reduced proliferation, their growth rate gradually increased and the cells showed signs of malignant transformation.

Previous studies indicated that two other members of the sirtuin family – SIRT1 and SIRT3 – have tumor suppressor functions. These findings suggest that a third member of this protein family acts as a tumor suppressor.

“You don’t normally find families of tumor suppressor genes,” Gius said. “They’re kind of lone wolves…it’s just not common to find a family of (tumor suppressor) genes, especially ones connected to aging.”

Because the mammary tumors that develop in female mice appear similar to the most common type of breast cancer (luminal breast cancers), Gius believes these mice could provide a much-needed animal model for that disease.

His group plans to investigate whether SIRT2 is a “driver” of luminal breast cancer and, if so, to use the mice as a model for investigating chemopreventive agents.

“Ultimately, we could possibly identify subgroups of women who might benefit from the agents we validate in mice,” he said.

The research was supported by grants from the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases, the National Cancer Institute, the National Center for Research Resources, and from the Department of Defense.

Contact: Melissa Marino
melissa.marino@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center

TITLE: Signaling via the prostaglandin E2 receptor EP4 exerts neuronal and vascular protection in a mouse model of cerebral ischemia

AUTHOR CONTACT:
Katrin Andreasson
Stanford University School of Medicine, Stanford, California, USA.
Phone: 650.723.1922; Fax: 650.498.6262; E-mail: kandreas@stanford.edu.

View this article at: http://www.jci.org/articles/view/46279?key=403ec32a48be38dd5d20

Contact: Karen Honey
press_releases@the-jci.org
734-546-5242
Journal of Clinical Investigation