Mouse brain cells live long and prosper

Mouse brain cells scamper close to eternal life: They can actually outlive their bodies. Mouse neurons transplanted into rat brains lived as long as the rats did, surviving twice as long as the mouse’s average life span, researchers report online February 25 in the Proceedings of the National Academy of Sciences.

The findings suggest that long lives might not mean deteriorating brains. “This could absolutely be true in other mammals — humans too,” says study author Lorenzo Magrassi, a neurosurgeon at the University of Pavia in Italy.

The findings are “very promising,” says Carmela Abraham, a neuroscientist at Boston University. “The question is: Can neurons live longer if we prolong our life span?” Magrassi’s experiment, she says, suggests the answer is yes.

One theory about aging, Magrassi says, is that every species has a genetically determined life span and that all the cells in the body wear out and die at roughly the same time. For the neurons his team studied, he says, “We have shown that this simple idea is certainly not true.”

Magrassi’s team surgically transplanted neurons from embryonic mice with an average life span of 18 months into rats. To do so, the researchers slipped a glass microneedle through the abdomens of anesthetized pregnant mice. Then, using a dissecting microscope and a tool to illuminate the corn-kernel-sized mouse embryos, the researchers scraped out tiny bits of brain tissue and injected the neurons into fetal rat brains. After the rat pups were born, Magrassi and colleagues waited as long as three years, until the animals were near death, to euthanize the rats and dissect their brains.

The transplanted mouse cells had linked up with the rat brain cells and developed into mature, working neurons, though they did retain their characteristic small size. Also, because Magrassi’s team had tagged the mouse cells to glow green, the researchers could distinguish between mouse and rat neurons. The mouse cells lived twice as long as they would have in a mouse brain, and they showed signs of aging similar to those of neighboring rat neurons.

Figuring out what’s helping the neurons survive could lead researchers to treatments for human neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, Magrassi says.

Researchers identify potential target for age-related cognitive decline

Cognitive decline in old age is linked to decreasing production of new neurons. Scientists from the German Cancer Research Center have discovered in mice that significantly more neurons are generated in the brains of older animals if a signaling molecule called Dickkopf-1 is turned off. In tests for spatial orientation and memory, mice in advanced adult age whose Dickkopf gene had been silenced reached an equal mental performance as young animals.

The hippocampus – a structure of the brain whose shape resembles that of a seahorse – is also called the “gateway” to memory. This is where information is stored and retrieved. Its performance relies on new neurons being continually formed in the hippocampus over the entire lifetime. “However, in old age, production of new neurons dramatically decreases. This is considered to be among the causes of declining memory and learning ability”, Prof. Dr. Ana Martin-Villalba, a neuroscientist, explains.

Martin-Villalba, who heads a research department at the German Cancer Research Center (DKFZ), and her team are trying to find the molecular causes for this decrease in new neuron production (neurogenesis). Neural stem cells in the hippocampus are responsible for continuous supply of new neurons. Specific molecules in the immediate environment of these stem cells determine their fate: They may remain dormant, renew themselves, or differentiate into one of two types of specialized brain cells, astrocytes or neurons. One of these factors is the Wnt signaling molecule, which promotes the formation of young neurons. However, its molecular counterpart, called Dickkopf-1, can prevent this.

"We find considerably more Dickkopf-1 protein in the brains of older mice than in those of young animals. We therefore suspected this signaling molecule to be responsible for the fact that hardly any young neurons are generated any more in old age." The scientists tested their assumption in mice whose Dickkopf-1 gene is permanently silenced. Professor Christof Niehrs had developed these animals at DKFZ. The term "Dickkopf" (from German "dick" = thick, "Kopf" = head) also goes back to Niehrs, who had found in 1998 that this signaling molecule regulates head development during embryogenesis.

Discovery opens the door to a potential ‘molecular fountain of youth’

A new study led by researchers at the University of California, Berkeley, represents a major advance in the understanding of the molecular mechanisms behind aging while providing new hope for the development of targeted treatments for age-related degenerative diseases.

Researchers were able to turn back the molecular clock by infusing the blood stem cells of old mice with a longevity gene and rejuvenating the aged stem cells’ regenerative potential. The findings were published online in the journal Cell Reports.

The biologists found that SIRT3, one among a class of proteins known as sirtuins, plays an important role in helping aged blood stem cells cope with stress. When they infused the blood stem cells of old mice with SIRT3, the treatment boosted the formation of new blood cells, evidence of a reversal in the age-related decline in the old stem cells’ function.

“We already know that sirtuins regulate aging, but our study is really the first one demonstrating that sirtuins can reverse aging-associated degeneration, and I think that’s very exciting,” said study principal investigator Danica Chen, UC Berkeley assistant professor of nutritional science and toxicology. “This opens the door to potential treatments for age-related degenerative diseases.”

Poor sleep in old age prevents the brain from storing memories

The connection between poor sleep, memory loss and brain deterioration as we grow older has been elusive. But for the first time, scientists at the University of California, Berkeley, have found a link between these hallmark maladies of old age. Their discovery opens the door to boosting the quality of sleep in elderly people to improve memory.

UC Berkeley neuroscientists have found that the slow brain waves generated during the deep, restorative sleep we typically experience in youth play a key role in transporting memories from the hippocampus – which provides short-term storage for memories – to the prefrontal cortex’s longer term “hard drive.”

However, in older adults, memories may be getting stuck in the hippocampus due to the poor quality of deep ‘slow wave’ sleep, and are then overwritten by new memories, the findings suggest.

“What we have discovered is a dysfunctional pathway that helps explain the relationship between brain deterioration, sleep disruption and memory loss as we get older – and with that, a potentially new treatment avenue,” said UC Berkeley sleep researcher Matthew Walker, an associate professor of psychology and neuroscience at UC Berkeley and senior author of the study published in the journal Nature Neuroscience.

Scientists Work To Unravel Mystery Behind Woman Who Doesn’t Grow

Twenty year old Brooke Greenberg hasn’t grown since age five. For the last 15 years mystified doctors have been unable to explain the cause for Brooke’s disorder that has kept her aging in check. At age twenty, she maintains the physical and mental appearance of a toddler.

Eric Shadt wants to solve this most bizarre of medical mysteries. Director of the Icahn Institute for Genomics and Multiscale Biology at the Mount Sinai Medical Center in New York, Shadt is leading research to uncover the genetic cause for Brooke’s condition.

Because hormones control many of the maturation processes, one of the first things the research team looked at was to see if Brooke’s own hormone levels might be abnormal. In a piece he wrote on Katie Couric’s website on whose show he and the Greenberg family recently appeared, Shadt explained that Brooke “has no apparent abnormalities in her endocrine system, no gross chromosomal abnormalities, or any of the other disruptions known to occur in humans that can cause developmental issues.”

The researchers are now painstakingly analyzing Brooke’s entire genome in search of unique mutations. Needless to say, it is a formidable undertaking. “Cracking the code on Brooke’s condition,” Shadt wrote, “is the proverbial searching for a needle in a haystack, since likely there is one or a small number of letters changed in Brooke’s genome that has caused her condition.”

How the brain copes with multi-tasking alters with age

The pattern of blood flow in the prefrontal cortex in the brains alters with age during multi-tasking, finds a new study in BioMed Central’s open access journal BMC Neuroscience. Increased blood volume, measured using oxygenated haemoglobin (Oxy-Hb) increased at the start of multitasking in all age groups. But to perform the same tasks, healthy older people had a higher and more sustained increase in Oxy-Hb than younger people.

Age related changes to the brain occur earliest in the prefrontal cortex, the area of the brain associated with memory, emotion, and higher decision making functions. It is changes to this area of the brain that are also associated with dementia, depression and other neuropsychiatric disorders. Some studies have shown that regular physical activity and cognitive training can prevent cognitive decline (use it or lose it!) but to establish what occurs in a healthy aging brain researchers from Japan and USA have compared brain activity during single and dual tasks for young (aged 21 to 25) and older (over 65) people.

Near infrared spectroscopy (NIRS) measurements of Oxy-Hb showed that blood flow to the prefrontal cortex was not affected by the physical task for either age group but was affected by the mental task. For both the young and the over 65s the start of the calculation task  coincided with an increase in blood volume which reduced to baseline once the task was completed.

The main difference between the groups was only seen when performing the physical and mental tasks at the same time - older people had a higher prefrontal cortex response which lasted longer than the younger group.

Hironori Ohsugi, from Seirei Christopher University, and one of the team who performed this research explained “From our observations during the dual task it seems that the older people turn their attention to the calculation at the expense of the physical task, while younger people are able to maintain concentration on both. Since our subjects were all healthy it seems that this requirement for increased activation of the prefrontal cortex is part of normal decrease in brain function associated with aging. Further study will show whether or not dual task training can be used to maintain a more youthful brain.”

(Image: Photos.com)

Study shows cogntive benefit of lifelong bilingualism

Seniors who have spoken two languages since childhood are faster than single-language speakers at switching from one task to another, according to a study published in the January 9 issue of The Journal of Neuroscience. Compared to their monolingual peers, lifelong bilinguals also show different patterns of brain activity when making the switch, the study found.

The findings suggest the value of regular stimulating mental activity across the lifetime. As people age, cognitive flexibility — the ability to adapt to unfamiliar or unexpected circumstances — and related “executive” functions decline. Recent studies suggest lifelong bilingualism may reduce this decline — a boost that may stem from the experience of constantly switching between languages. However, how brain activity differs between older bilinguals and monolinguals was previously unclear.

In the current study, Brian T. Gold, PhD, and colleagues at the University of Kentucky College of Medicine, used functional magnetic resonance imaging (fMRI) to compare the brain activity of healthy bilingual seniors (ages 60-68) with that of healthy monolingual seniors as they completed a task that tested their cognitive flexibility. The researchers found that both groups performed the task accurately. However, bilingual seniors were faster at completing the task than their monolingual peers despite expending less energy in the frontal cortex — an area known to be involved in task switching.

“This study provides some of the first evidence of an association between a particular cognitively stimulating activity — in this case, speaking multiple languages on a daily basis — and brain function,” said John L. Woodard, PhD, an aging expert from Wayne State University, who was not involved with the study. “The authors provide clear evidence of a different pattern of neural functioning in bilingual versus monolingual individuals.”

The researchers also measured the brain activity of younger bilingual and monolingual adults while they performed the cognitive flexibility task.

Overall, the young adults were faster than the seniors at performing the task. Being bilingual did not affect task performance or brain activity in the young participants. In contrast, older bilinguals performed the task faster than their monolingual peers and expended less energy in the frontal parts of their brain.

“This suggests that bilingual seniors use their brains more efficiently than monolingual seniors,” Gold said. “Together, these results suggest that lifelong bilingualism may exert its strongest benefits on the functioning of frontal brain regions in aging.”

(Image: Harriet Russell)

Why Do Age-Related Macular Degeneration Patients Have Trouble Recognizing Faces?

Abnormalities of eye movement and fixation may contribute to difficulty in perceiving and recognizing faces among older adults with age-related macular degeneration (AMD), suggests a study “Abnormal Fixation in Individuals with AMD when Viewing an Image of a Face” appearing in the January issue of Optometry and Vision Science, official journal of the American Academy of Optometry. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

Unlike people with normal vision focus, those with AMD don’t focus on “internal features” (the eyes, nose and mouth) when looking at the image of a face, according to the study by William Seiple, PhD, and colleagues of Lighthouse International, New York.

When Viewing Famous Face, AMD Patients Focus on External Features

The researchers used a sophisticated technique called optical coherence tomography/scanning laser ophthalmoscopy (OCT-SLO) to examine the interior of the eye in nine patients with AMD. Age-related macular degeneration is the leading cause of vision loss in older adults. It causes gradual destruction of the macula, leading to blurring and loss of central vision.

Previous studies have suggested that people with AMD have difficulty perceiving faces. To evaluate the possible role of abnormal eye movements, Dr Seiple and colleagues used the OCT-SLO equipment to make microscopic movies of the interior of the eye (fundus, including the retina and macula) as the patients viewed one of the world’s most famous faces: the Mona Lisa.

This technique allowed the researchers to record eye movements and where the patients looked (fixations) while looking at the face. They compared the findings in AMD patients to a control group of subjects with normal vision.

The results showed significant differences in eye movement patterns and fixations between groups. The AMD patients had fewer fixations on the internal features of the Mona Lisa’s face—eyes, nose, and mouth. For controls, an average of 87 percent of fixations were on internal features, compared to only 13 percent on external features. In contrast, for AMD patients, 62 percent of fixations were on internal features while 38 percent were on external features.

The normal controls also tended to make fewer and shorter eye movements (called saccades) than AMD patients. The differences between groups did not appear to be related to the blurring of vision associated with AMD.

Some older adults with AMD report difficulties perceiving faces. While the problem in “processing faces” is certainly related to the overall sensory visual loss, the new evidence suggests that specific patterns of eye movement abnormalities may also play a role.

Dr Seiple and colleagues note that “abnormal scanning patterns when viewing faces” have also been found in other conditions associated with difficulties in face perception, including autism, social phobias, and schizophrenia. The authors discuss the possible mechanisms of the abnormal scanning patterns in AMD, involving the complex interplay between the eyes and brain in governing eye movement and interpreting visual information.

A previous study suggested that drawing attention to specific characteristics—such as the internal facial features—may increase fixations on internal features and improve face perception. Dr Seiple and coauthors conclude, “That report gives hope that eye movement control training and training of allocation of attention could improve face perception and eye scanning behavior in individuals with AMD.”