NEW EVIDENCE OF AGE-RELATED DECLINE IN THE BRAIN'S MASTER CIRCADIAN CLOCK
ScienceDaily (July 18, 2011) - A new study of the brain's master circadian clock -- known as the suprachiasmatic nucleus, or SCN -- reveals that a key pattern of rhythmic neural activity begins to decline by middle age. The study, whose senior author is UCLA Chancellor Gene Block, may have implications for the large number of older people who have difficulty sleeping and adjusting to time changes.
"Aging has a profound effect on circadian timing," said Block, a professor of psychiatry and biobehavioral sciences and of physiological science. "It is very clear that animals' circadian systems begin to deteriorate as they age, and humans have enormous problems with the quality of their sleep as they age, difficulty adjusting to time-zone changes and difficulty performing shift-work, as well as less alertness when awake. There is a real change in the sleep-wake cycle.
"The question is, what changes in the nervous system underlie all of that? This paper suggests a primary cause of at least some of these changes is a reduction in the amplitude of the rhythmic signals from the SCN."
The SCN, located in the hypothalamus, is the central circadian clock in humans and other mammals and controls not only the timing of the sleep-wake cycle but also many other rhythmic and non-rhythmic processes in the body.
The UCLA research team examined the SCN in mice and found that while critical neural activity rhythms were already disrupted in middle age, the molecular mechanisms that generate these rhythms were not significantly altered.
"These results indicate that the outputs of the central circadian clock start to decline in middle age and suggest that the same may be true in humans," said study co-author Christopher Colwell, a UCLA professor of psychiatry and biobehavioral sciences who has conducted research with Block for many years. "Before this study, we did not know that the SCN was the site where the decline occurs."
In a technical tour de force, the research team successfully recorded electrical activity from the brain's SCN -- not in a Petri dish but in living animals. The research marks the first time this has been achieved in middle-aged animals and the first time scientists have watched the central biological clock of aging animals in action. The study was published July 13 in the Journal of Neuroscience, the journal of the Society for Neuroscience.
The scientists studied young mice, which were just a few months old, and middle-aged mice, which were more than a year old. SCN brain cells are electrically active during the day and electrically silent during the night in younger animals and younger people, the researchers said, but that difference is reduced with aging.
"The changes we observed in the electrical rhythm between the young and middle-aged animals, which are quite dramatic, occur even though we do not see significant changes in the underlying molecular rhythm," Block said. "Our hypothesis is that the age-related changes in the circadian timing system are primarily occurring, at least initially, at the level of the electrical output signaling, perhaps mediated by changes in the cell-membrane properties of SCN clock cells. This is good news, because it points where in the cell to look for the age-related 'lesion' and thus helps inform what type of measures may be available to reduce these age-related deficits."
Block and Colwell suspect the process is similar in humans.
The SCN keeps the system of multiple distributed circadian oscillators in synchrony, but disruptions in the SCN lead to disrupted sleep, as well as dysfunction in memory, the cardiovascular system, and the body's immune response and metabolism.
The SCN, Block said, can be imagined as a heavy pendulum that controls many light pendulums (oscillators), with rubber bands between them.
"If the central clock weakens, it's effectively like making those rubber bands thinner and weaker," Block said. "When the SCN ages and those rubber bands become weaker, it becomes hard for the SCN to synchronize all of these other oscillators."
In the young mice, the scientists found high levels of activity during the day and much lower activity levels during the night. In middle-aged mice, there was not nearly as large a difference in activity between the day and the night.
"In the middle-aged mice, they still have a circadian rhythm, but the amplitude is reduced," Block said. "During the nighttime, when electrical impulse activity levels are usually fairly low, the levels have increased. Thus, the difference between the highest levels of activity during the daytime and the lowest levels of activity during the nighttime is much smaller in the middle-aged mice."
Large numbers of people over the age of 65 regularly take sleeping pills, but the effects of taking such pills over many years is not known, said Colwell, who hopes the new research will lead to other options for getting a good night's sleep.
Colwell, Block and their team plan to pursue follow-up research on treatment options that could enhance the function of the circadian system with aging. They are studying the specific membrane channel changes in the SCN that are responsible for the electrical rhythm and also are looking at the circadian regulation of the heart and the mechanisms underlying neural activity rhythms in the SCN.
Their research could potentially lead to new ways of boosting the circadian output. It is possible, Colwell and Block said, that relatively simple approaches could be beneficial, such as exercising early in the morning, getting regular exposure to bright light, eating meals at consistent times and, when traveling, eating meals at the appropriate local time, regardless of whether one is hungry then.
Possible interventions may involve discovering ways to improve the sleep cycle of aging people and their ability to better handle time-zone changes, perhaps by boosting the amplitude of the SCN. New pharmaceutical approaches may be developed, the scientists said. Future research may reveal which approaches are likely to be most effective.
Co-authors of the study included lead scientist Takahiro Nakamura, a former UCLA postdoctoral scholar in Colwell and Block's laboratory, who is currently on the faculty of Japan's Teikyo Heisei University; Takashi Kudo, a UCLA postdoctoral scholar; and Tamara Cutler, a UCLA undergraduate student who works in Colwell and Block's lab.
The research was funded by the National Institutes of Health and by UCLA.
Implications for patients with neurological disorders such as Parkinson's
In related research, Colwell and his colleagues have documented that changes similar to those that occur as we age also occur in mouse models of neurodegenerative disorders like Huntington's disease and Parkinson's disease.
"With many neurological disorders, patients have a hard time sleeping during the night and staying awake during the day," said Colwell, who was a postdoctoral fellow in Block's lab in the early 1990s at the University of Virginia. "One of the main clinical complaints of patients with Huntington's disease and Parkinson's disease is they cannot sleep and do not respond well to sleeping pills. We think the same dysfunction we see with normal aging occurs much earlier and more severely with these patients, and we hope that the treatment strategies we develop for aging can be applied to help patients with neurodegenerative diseases as well. If we learn what is going wrong, then we may be able to develop treatments."
Colwell's research on Huntington's disease was published earlier this year in the journal Experimental Neurology, and his research on Parkinson's has been accepted for publication in the same journal.
Undergraduate works in laboratory of Colwell and Block
Tamara Cutler, a UCLA senior majoring in neuroscience and physiological science, co-authored the new SCN research. So what is it like for an undergraduate to conduct research with distinguished scientists, including the university's chancellor?
"Working in the laboratory of Professor Colwell and Chancellor Block has been rewarding, demanding and priceless," Cutler said. "I joined the lab with the usual book knowledge of a life sciences student, a nearly boundless enthusiasm for research and a love for solving puzzles of every kind. Professor Colwell, Chancellor Block, the postdocs (Dawn Loh and Takshi Kudo) and the graduate students all invested time in my training and provided me with many fantastic opportunities to develop a strong set of skills.
"Since joining the lab, I have learned numerous techniques and been allowed to perform my own experiments from start to finish while working on my honors thesis. I have been treated as a valuable member of the lab and have been encouraged to make intellectual contributions to our research, which I am certain has greatly accelerated my growth as a scientist. Being granted a co-authorship on this manuscript as an undergraduate is very meaningful to me because it is not handed out lightly here.
"Dr. Colwell and Chancellor Block are really extraordinary scientists and renowned figures in the circadian research community, and it has been my great privilege to learn from them. I know my time here in the Colwell-Block lab has transformed me from someone who merely learns science into someone who can actually do science. I still have years of training ahead, but the journey thus far has been priceless.
WORLD POPULATION TO SURPASS 7 BILLION IN 2011; EXPLOSIVE POPULATION GROWTH MEANS CHALLENGES FOR DEVELOPING NATIONS
Science Daily (July 28, 2011) - Global population is expected to hit 7 billion later this year, up from 6 billion in 1999. Between now and 2050, an estimated 2.3 billion more people will be added -- nearly as many as inhabited the planet as recently as 1950. New estimates from the Population Division of the Department of Economic and Social Affairs of the United Nations also project that the population will reach 10.1 billion in 2100.
These sizable increases represent an unprecedented global demographic upheaval, according to David Bloom, Clarence James Gamble Professor of Economics and Demography at the Harvard School of Public Health, in a review article published July 29, 2011 in Science.
Over the next forty years, nearly all (97%) of the 2.3 billion projected increase will be in the less developed regions, with nearly half (49%) in Africa. By contrast, the populations of more developed countries will remain flat, but will age, with fewer working-age adults to support retirees living on social pensions.
"Although the issues immediately confronting developing countries are different from those facing the rich countries, in a globalized world demographic challenges anywhere are demographic challenges everywhere," said Bloom.
The world's population has grown slowly for most of human history. It took until 1800 for the population to hit 1 billion. However, in the past half-century, population jumped from 3 to 7 million. In 2011, approximately 135 million people will be born and 57 million will die, a net increase of 78 million people.
Considerable uncertainty about these projections remains, Bloom writes. Depending on whether the number of births per woman continues to decline, the ranges for 2050 vary from 8.1 to 10.6 billion, and the 2100 projections vary from 6.2 to 15.8 billion.
Population trends indicate a shift in the "demographic center of gravity" from more to less developed regions, Bloom writes. Already strained, many developing countries will likely face tremendous difficulties in supplying food, water, housing, and energy to their growing populations, with repercussions for health, security, and economic growth.
"The demographic picture is indeed complex, and poses some formidable challenges," Bloom said. "Those challenges are not insurmountable, but we cannot deal with them by sticking our heads in the sand. We have to tackle some tough issues ranging from the unmet need for contraception among hundreds of millions of women and the huge knowledge-action gaps we see in the area of child survival, to the reform of retirement policy and the development of global immigration policy. It's just plain irresponsible to sit by idly while humankind experiences full force the perils of demographic change."
'GOOD FAT' MOST PREVALENT IN THIN CHILDREN
ScienceDaily (Aug. 11, 2011) - Researchers at Joslin Diabetes Center and Children's Hospital Boston have shown that a type of "good" fat known as brown fat occurs in varying amounts in children -- increasing until puberty and then declining -- and is most active in leaner children.
The study used PET imaging data to document children's amounts and activity of brown fat, which, unlike white fat, burns energy instead of storing it. Results were published in The Journal of Pediatrics.
"Increasing the amount of brown fat in children may be an effective approach at combating the ever increasing rate of obesity and diabetes in children," said Aaron Cypess, MD, PhD, an assistant investigator and staff physician at Joslin and senior author of the paper.
In 2009, Cypess' team demonstrated in The New England Journal of Medicine for the first time that brown fat is metabolically active in adult humans. Previously, it was thought that brown fat was present only in babies and children. Their study showed it was found in between 3 and 7.5 percent of adults, with higher rates among women.
In this new study, the researchers reviewed PET scans that had been conducted on 172 children ages 5 to 21 at Children's Hospital Boston. Active brown fat was detected in 44 percent of the children, with the rate about the same for girls and boys. Children aged 13 to 15 had the highest percentage of detectable brown fat and the highest brown fat activity. But in addition, body mass index (BMI) was correlated inversely with brown fat activity, meaning that the thinnest children had the highest brown fat activity.
While the 2009 study of adults showed brown fat was more active in cold weather, in keeping with its role of burning energy to generate heat, the new study in children showed outdoor temperature had no effect on brown fat activity.
The increase in brown fat activity from childhood to adolescence and its inverse correlation with obesity suggest brown fat may play a prominent role in pediatric metabolism, energy balance and weight regulation, the authors said.
"We believe that the ability to non-invasively evaluate brown fat activity in vivo with PET imaging provides a better understanding of its prominent role in pediatric physiology, and may possibly provide insights into the treatment of childhood obesity," said first author Laura Drubach, MD, of Children's Hospital program in Nuclear Medicine and Molecular Imaging.
Cypess said the goal is to first search for nonpharmacological ways to increase brown fat activity, perhaps by setting indoor temperatures colder in homes where obese children live. Perhaps certain foods could also play a role in increasing brown fat levels, he said. If not, the development of new drugs might be the answer, he added.
A 2010 Joslin study identified cells in mice that can be triggered to transform into brown fat.
"We might be able to combat the obesity and diabetes epidemics if we find safe ways of increasing brown fat activity," Cypess said. "This might be an additional tool in the fight." However, he said there are still many questions to be answered. For example, it is not known whether the relationship between BMI and brown fat is that children have more brown fat because they are thin or if having more brown fat causes children to be thin. "That's the billion dollar question," he said. "But we do know that brown fat is a core component of pediatric and likely adult metabolism."
RECENT DEVELOPMENTS MENTAL HEALTH DISORDERS AMONG WOMEN
SYDNEY, Aug. 5 (UPI) -- Rape, sexual assault, intimate partner violence and stalking increase the lifetime risk of mental health disorders among women, Australian researchers say.
Study leader Dr. Susan Rees of the University of New South Wales' School of Psychiatry and colleagues analyzed survey data of 4,451 women ages 16-85.
About 15 percent of Australian women report sexual assault, while 9 percent report being raped, 8 percent report physical intimate partner violence and 10 percent report stalking.
The study, published in the Journal of the American Medical Association, shows the four most common types of gender-based violence are strongly associated with a wide range of problems for women, including more severe current mental disorder, higher rates of three or more lifetime mental disorders, physical disability, mental disability, impaired quality of life and overall disability.
"It was the strength of these associations that was most shocking. There is an overwhelming link between gender violence and key indicators of women's mental health, well being and risk of suicide attempts," Rees says in a statement. "For women exposed to two types of gender-based violence the lifetime rate of mental disorder was 69 percent and for three or more types of gender-based violence, it was 89.4 percent. This compares with a rate of 28 percent for women who have not experienced violence. The link with gender-based violence was particularly strong for post-traumatic stress disorder."
