Culture

A study conducted in Brazil by researchers at the University of São Paulo (USP) and the University of Campinas (UNICAMP) shows that if 25% of an Atlantic rainforest fragment that is approximately 1 hectare is deforested, then the local temperature will increase by 1 °C. Clear-cutting the entire fragment would increase the local temperature by as much as 4 °C. The findings are published in the journal PLOS ONE.

"We were able to detect the warming effects of the climate due to the deforestation of Atlantic rainforest fragments, of which there are many in Southeast Brazil," Humberto Ribeiro da Rocha, principal investigator of the study, told. Rocha is a professor at the University of São Paulo Institute of Astronomy, Geophysics and Atmospheric Sciences (IAG-USP).

The investigation was conducted under the aegis of two projects supported by São Paulo Research Foundation
- FAPESP, one associated with its Research Program on Global Climate Change (RPGCC) and the other with its Research Program on Biodiversity Characterization, Conservation, Restoration and Sustainable Use (BIOTA-FAPESP).

According to Rocha, scientific evidence is already available that shows that the destruction of tropical forests leads to warmer air at a local scale, but this evidence is based on measurements taken in large areas, mainly by research conducted in the Amazon.

"No one had ever produced detailed information on the deforestation of small fragments or studies that take into account different levels of anthropization [transformation of the environment by human activity]," said Rocha, who is a member of the RPGCC's steering committee.

To fill this research gap, researchers analyzed the relationship between the degree of deforestation and local temperature increases in Atlantic rainforest remnants located in Serra do Mar, a mountain range that stretches along the northern coast of São Paulo state.

Land surface temperature (LST) was estimated using heat flux data continuously recorded around the globe by infrared optical sensors such as those on board NASA's Landsat Earth observation satellites.

Based on these data, the researchers calculated an annual average LST for tens of thousands of Atlantic rainforest samples, each with an area of approximately 1 hectare. The forest cover in these areas ranged from the entirety of the area being covered to no area having forest cover (deforested). These areas also displayed different degrees of anthropization, with a 1% variation gradient.

The calculations were performed during the PhD research of Raianny Leite do Nascimento Wanderley, under Rocha's supervision. They showed higher temperatures in less forested areas. Each 25% increase in the destruction of native vegetation resulted in an LST increase of 1 °C; thus, total deforestation was correlated with a warming of 4 °C.

"This detected pattern is interpreted as characterizing the impact of forest cover loss on the microclimate," Rocha said.

Impact on the forest

According to the researchers, the Atlantic rainforest fragments they studied were located at relatively higher altitudes and had proportionately more carbon stored in the ground than those in the Amazon rainforest areas. Deforestation of Atlantic rainforest areas can therefore jeopardize the biome's carbon balance.

"The Atlantic rainforest is currently in equilibrium and may even be marginally absorbing carbon from the atmosphere but could become a source of carbon emissions," said Carlos Joly (https://bv.fapesp.br/en/pesquisador/283/carlos-alfredo-joly/), a professor at UNICAMP and one of the authors of the study. Joly is a member of BIOTA-FAPESP's steering committee.

Rising temperatures in these forest fragments affect plant respiration more than photosynthesis. This also contributes to the release of larger amounts of carbon from the forest into the atmosphere, Joly explained.

"The two processes combined create a hazardous synergy that leads to a rise in carbon emissions from the forest to the atmosphere," he said.

The effects of deforestation-driven warming in Atlantic rainforest fragments may vary from one tree species to another, he added. Pioneer species, which survive under adverse conditions owing to their high reproductive capacity, usually display greater resilience to temperature changes.

"We don't have enough data yet to predict how long it will take, but in the long run, rising temperatures in Atlantic rainforest fragments due to deforestation could certainly influence the survival of tree species in the forest, albeit some species more than others," he said.

"The proportion of typical mature forest species may diminish, while that of pioneer or initial secondary species, which are more plastic, could increase."

Functions impaired

Considered one of the world's richest and most endangered forests, the Atlantic rainforest occupies 15% of Brazil's land mass in an area that is home to 72% of the population. The biome decreased by 113 square kilometers between 2017 and 2018, according to recent data from the Atlas da Mata Atlântica based on continuous monitoring by NGO Fundação SOS Mata Atlântica in partnership with the National Space Research Institute (INPE).

In addition to the impact on biodiversity, the researchers stressed that even small-scale deforestation impairs important ecosystem services provided by the Atlantic rainforest, such as heat regulation.

"The forest is extremely important to maintaining milder temperatures on the local and regional scale. Changes in its functioning could disrupt this type of ecosystem service," Joly said.

Water supply may also be affected. The Atlantic rainforest is home to seven of Brazil's nine largest drainage basins, where rivers originate that flow into reservoirs that are responsible for almost 60% of the nation's hydroelectric power and supply water to 130 million people.

"The Atlantic rainforest doesn't produce water but protects the springs and permits the storage of water in reservoirs for consumption, power generation, agricultural irrigation and fishing, among other activities," Joly said.

Located in extremely rugged terrain, the Atlantic rainforest helps prevent landslides at times of heavy rain. "Destruction of these forest fragments or changes in their functioning could greatly diminish this protection," Joly said.

Deforestation of the biome, now reduced to 12.4% of its original size, is more severe in São Paulo state than in other areas owing to the construction of roads, gas pipelines and other kinds of infrastructure, he added. This area has also suffered from urban expansion, including the construction of both shantytowns and high-income gated communities.

As one of the most endangered biomes in South America, the Atlantic rainforest has been a focus for numerous studies regarding restoration in recent years. Most of the studies have been conducted by researchers affiliated with BIOTA-FAPESP, according to Joly.

The largest initiative to restore the biome is governed by the Atlantic Rainforest Restoration Pact, launched in 2009 as a multi-stakeholder movement to restore 15 million hectares by 2050.

"A great deal of knowledge has been acquired regarding restoration of the Atlantic rainforest. Evidently, we won't be able to replace everything that has been lost, but at least some of the biome's functions can be restored," Joly said.

(Boston)--There is a trend in modern medical school curriculum design to integrate the basic sciences and clinical sciences. Integrating basic science education with its clinical application from the initial stages of learning is thought to improve retention of information and facilitate the transfer of knowledge to the clinical setting.

Basic science educators are not clinicians, yet to accommodate integration they must adjust their content to mesh appropriately with its clinical application. While achievable, this is a challenge that requires intentional effort on the part of the basic science educators.

Researchers from Boston University School of Medicine (BUSM) believe a practical way to facilitate curricular integration is to create opportunities for basic science educators to learn about the clinical application of their area of expertise through shadowing and collaborations with clinician educators and to pair these initiatives with training in effective medical education practices.

"By shadowing clinician educators during patient care or clinical teaching, basic scientists can observe how clinicians apply basic science concepts. Such opportunities help basic science educators better understand how to prioritize and communicate information that has long-term relevance for their learners," explains corresponding author M. Isabel Dominguez, PhD, assistant professor of medicine at BUSM.

Most medical schools are wrestling with the challenge of integration in medical education. Dominguez along with co-author Ann Zumwalt, PhD, BUSM associate professor of anatomy & neurobiology, discuss practical strategies to develop these opportunities and how they bene?t educators.

They believe there are numerous ways that both individuals and institutions can create and facilitate such faculty development opportunities, both for basic science faculty who are full-time educators and those who engage in medical education part time. "Ultimately, these interventions and initiatives will bene?t both the institution's curriculum and the student learners impacted by the curriculum," adds Zumwalt.

Researchers at the University of Illinois at Urbana-Champaign are using a new application of an existing imaging technique that may help detect tumors in humans.

The technique, super-resolution ultrasound localization microscopy, was used to visualize the distribution of blood vessels and measure oxygen levels in tumors. The study was carried out in chicken embryos, but the researchers hope to extend the studies in humans.

The paper "Ultrasound localization microscopy of renal tumor xenografts in chicken embryo is correlated to hypoxia" was published in Scientific Reports.

ULM uses microbubbles, which are the size of red blood cells, to image tissues.

"We track these bubbles as they flow through blood vessels to obtain a higher resolution image than traditional ultrasounds," said Matthew Lowerison, a postdoctoral research associate in the Song Research Group at the Beckman Institute for Advanced Science and Technology.

Researchers have long known that tumors can be resistant to therapy because of their lower oxygen levels. "Red blood cells can flow through straight blood vessels quickly and efficiently. As a result, the delivery of oxygen and nutrients is efficient," Lowerison said. "In contrast, the blood vessels in tumors are twisted onto each other. It is chaotic and disorganized, and the delivery of oxygen is inefficient."

The members of the Song group have used ULM to demonstrate that oxygen levels are lower in tumors compared to healthy tissue.

"This study is unique because we can image tissue that is deeper inside humans without losing image resolution," said Pengfei Song, an assistant professor of electrical and computer engineering and a full-time faculty member at the Beckman Institute. "Although this technique requires us to inject these microbubbles, they do not have toxicity problems as other imaging agents. Additionally, the microbubbles are approved by the Food and Drug Administration and are widely used in clinic around the world."

Currently the main challenge posed by this technique is the acquisition time. "We need to have a large data set to process the images," Lowerison said. "Although as engineers we are focused on getting the best possible images we can, this technique might work for doctors who want a better vascular image than the conventional imaging methods."

"We are starting to see good results when we use artificial intelligence and machine learning with these technologies, which can help to make this process faster," Song said. "Ultimately, we want to be able to use this technique in a clinical setting for cancer detection, diagnosis, and therapy evaluation."

An international team of scientists have discovered a new material that can be 3D printed to create tissue-like vascular structures.

In a new study published today in Nature Communications, led by Professor Alvaro Mata at the University of Nottingham and Queen Mary University London, researchers have developed a way to 3D print graphene oxide with a protein which can organise into tubular structures that replicate some properties of vascular tissue.

Professor Mata said: "This work offers opportunities in biofabrication by enabling simulatenous top-down 3D bioprinting and bottom-up self-assembly of synthetic and biological components in an orderly manner from the nanoscale. Here, we are biofabricating micro-scale capillary-like fluidic structures that are compatible with cells, exhibit physiologically relevant properties, and have the capacity to withstand flow. This could enable the recreation of vasculature in the lab and have implications in the development of safer and more efficient drugs, meaning treatments could potentially reach patients much more quickly."

Material with remarkable properties

Self-assembly is the process by which multiple components can organise into larger well-defined structures. Biological systems rely on this process to controllably assemble molecular building-blocks into complex and functional materials exhibiting remarkable properties such as the capacity to grow, replicate, and perform robust functions.

The new biomaterial is made by the self-assembly of a protein with graphene oxide. The mechanism of assembly enables the flexible (disordered) regions of the protein to order and conform to the graphene oxide, generating a strong interaction between them. By controlling the way in which the two components are mixed, it is possible to guide their assembly at multiple size scales in the presence of cells and into complex robust structures.

The material can then be used as a 3D printing bioink to print structures with intricate geometries and resolutions down to 10 ?m. The research team have demonstrated the capacity to build vascular-like structures in the presence of cells and exhibiting biologically relevant chemical and mechanical properties.

Dr. Yuanhao Wu is the lead researcher on the project, she said: "There is a great interest to develop materials and fabrication processes that emulate those from nature. However, the ability to build robust functional materials and devices through the self-assembly of molecular components has until now been limited. This research introduces a new method to integrate proteins with graphene oxide by self-assembly in a way that can be easily integrated with additive manufacturing to easily fabricate biofluidic devices that allow us replicate key parts of human tissues and organs in the lab."

Individuals who experience the loss of a partner are less likely to be diagnosed with melanoma but face an increased risk of dying from the disease, according to research published in the British Journal of Dermatology.

The researchers, led by the London School of Hygiene & Tropical Medicine and Aarhus University Hospital, investigated whether bereaved individuals had a higher risk of being diagnosed with, or dying from, melanoma than the non-bereaved. They used data from two large population-based studies between 1997 and 2017 in the UK and Denmark.

They found that melanoma patients who experienced bereavement had a 17% higher risk of dying from their melanoma compared with those who were not bereaved, with similar results seen in both the UK and Denmark.

This study also showed that those who had lost a partner were 12% less likely to be diagnosed with melanoma compared with non-bereaved persons, with 620 and 1667 bereaved diagnosed in the UK and Denmark respectively over the 20 year period, compared with 6430 and 16,166 non-bereaved.

While previous studies have suggested a link between various types of stress and progression of melanoma, which may have played a role in the finding, the researchers suggest that an alternative explanation could be that bereaved people no longer have a close person to help notice skin changes.

This delays detection of a possible melanoma, and therefore diagnosis, until the cancer has progressed to later stages, when it is generally more aggressive and harder to treat.

Each year, 197,000 people are diagnosed with melanoma globally. Melanoma makes up around 5% of all cancer cases in the UK and Denmark. The survival rate of melanoma patients is relatively high, depending on what stage the cancer is at detection. Early detection and treatment are crucial for improving survival.

Angel Wong, lead author and Research Fellow at the London School of Hygiene & Tropical Medicine, said:

"Many factors can influence melanoma survival. Our work suggests that melanoma may take longer to detect in bereaved people, potentially because partners play an important role in spotting early signs of skin cancer.

"Support for recently bereaved people, including showing how to properly check their skin, could be vital for early detection of skin cancer, and thus improved survival."

The researchers also encourage family members or caregivers to perform skin examinations for the remaining partner, and call for clinicians to lower their threshold for undertaking skin examinations in bereaved people.

They acknowledge the study's limitations, including the lack of information on some risk factors of melanoma, such as sun exposure or family history, but consider that this had limited impact on the conclusions drawn from this study.

Dr Walayat Hussain of the British Association of Dermatologists said:

"Detecting melanoma early can greatly improve survival and partners are key to this. Those without a partner should be vigilant in checking their skin, particularly in hard to reach locations such as the back, scalp, and ears.

"Skin cancer is a disease which is most common in older people, who are also most likely to be bereaved, so targeting skin checking advice at this group should be a priority."

Electrical stimulation benefited women with constipation in a recent clinical trial published in Alimentary Pharmacology & Therapeutics.

In the trial, 33 women with constipation that had not improved with standard treatment received either real or sham electrical stimulation on the stomach and back for 1 hour each day for 6 weeks. The women did not know whether they were receiving the real or the sham treatment. Treatment was successful in 53% of the women in the first group but only 12% in the second. Furthermore, the improvement in symptoms lasted for at least 3 months after the treatment ended, and there were no reported side effects.

"This treatment is very promising and offers patients a well-tolerated alternative to laxative medications," said lead author Judith S. Moore, PhD, RN, of Monash University in Australia.

Psychological stress has been proposed as a risk factor for melanoma, but clinical evidence is limited. A recent British Journal of Dermatology study funded by the European Academy of Dermatology and Venereology looked for a potential link between the death of a partner, which is one of the most stressful life events, and melanoma. The research was carried out by the London School of Hygiene & Tropical Medicine and Aarhus University Hospital in Denmark.

In the study, which included information from the UK Clinical Practice Research Datalink and Danish nationwide registries, investigators found that partner bereavement was linked with a decreased risk of being diagnosed with melanoma, but with an increased risk of dying after being diagnosed.

"The study findings are interesting and may relate to bereaved people no longer having someone to help with skin examinations, leading to delays in diagnosis, although we cannot rule out stress being important in melanoma progression," said senior author Sinéad Langan, PhD, of the London School of Hygiene and Tropical Medicine.

To address obesity worldwide, changes are needed in both the availability of treatments and the attitudes of clinicians. That's the conclusion of a survey-based study of health professionals.

In the Clinical Obesity study, investigators surveyed 274 respondents from a total of 68 low, middle, and high income countries. Respondents in most countries stated that there were professional guidelines for obesity treatment, but adequate services were lacking, especially in lower income countries and in rural areas of most countries.

Lack of treatment was attributed to a broad range of issues including: no clear care pathways from primary care to specialty services; absent or limited specialty services in some regions; potentially high costs to patients; long waiting times for surgery; and stigma or blame experienced by patients.

Few countries were willing to define obesity as a disease.

"The lack of investment in clinical services shows a critical failure of government to respect and protect our right to good health," said senior author Tim Lobstein, PhD, of the World Obesity Federation. "Without substantial investment in the treatment of obesity, the demands on health services will increase dramatically--not only because of the rising numbers of people suffering obesity and its consequences, but because the duration of experiencing obesity greatly increases the risk of more disabling diseases requiring greater intensity of interventions".

Use of antibiotics during pregnancy does not appear to affect children's weight in subsequent years, but use during infancy may increase their risk of becoming overweight or obese. The findings come from an analysis published in the journal Obesity.

When investigators examined all relevant published studies that looked at the use of antibiotics during pregnancy or infancy and children's later weight--which included 23 observational studies involving 1,253,035 participants--they did not find a link between prenatal antibiotic use and childhood overweight or obesity. An increased risk of overweight or obesity was seen in analyses limited to the use of antibiotics in the second trimester, however, as well as in the use of antibiotics during infancy.

"Antibiotics should be used more cautiously for children than pregnant women," said senior author Yong Xu, MD, PhD, of The Affiliated Hospital of Southwest Medical University, in China.

In a study of Americans over age 50 years who died between 2004 and 2014, individuals who were characterized as lonely based on survey results were burdened by more symptoms and received more intense end-of-life care compared with non-lonely people.

In the 2,896-participant study, which is published in the Journal of the American Geriatrics Society, one-third of adults were lonely. In addition to having an increased likelihood of experiencing burdensome symptoms at the end of life, lonely individuals were more likely to use life support in the last 2 years of life (35.5% versus 29.4%) and more likely to die in a nursing home (18.4% versus 14.2%) than non-lonely individuals.

"Loneliness is a pervasive psychosocial phenomenon with profound implications for the health and wellbeing of older adults throughout the life continuum, and particularly at the end of life," said lead author Nauzley Abedini, MD, MSc, of the University of Michigan. "We must do more--as healthcare providers, but also as a society--to screen for and intervene on loneliness not just during the dying process, but before the end of life period."

To quickly identify victims of the 2018 Camp Fire, the deadliest wildfire in California's history, researchers used a technique called Rapid DNA Identification that can provide results within hours, compared with months to years required of conventional DNA analysis.

As reported in the Journal of Forensic Sciences, Rapid DNA Identification was used in a rented recreational vehicle outside the Sacramento morgue. Sixty-nine sets of remains were assessed, and of these, 62 (89.9%) generated DNA profiles that were screened against 255 family reference samples. In total, 58 victims were identified using Rapid DNA.

This work represents the first use of Rapid DNA Identification in a mass casualty event. It has since been utilized in the Conception Dive Boat fire in 2019.

"Rapid DNA enabled Sacramento County and Butte County to support the loved ones of the victims of the devastating Camp Fire," said Richard F. Selden, MD, PhD, Founder of ANDE Corporation. "What we've learned from this tragedy is that Rapid DNA Identification can and should be used routinely in mass casualty victim identification. Furthermore, by bringing DNA analysis from the laboratories to the field, Rapid DNA Identification can help reduce sexual assault and human trafficking, fight terrorism, and exonerate the innocent."

Middle school football players greatly reduce the chance of head injuries if they wear padded helmets and use safe tackling and blocking techniques, according to Rutgers researchers.

The study was published in the journal Neurosurgery.

With youth players representing 70 percent of all amateur and professional football participants, attention is turning to the safety of the sport for younger players. Concussions and other head injuries in football and other contact sports among older athletes have been linked to cognitive problems, including dementia, depression and chronic traumatic encephalopathy, a degenerative brain disease.

"Parents are understandably concerned that their young football players are putting themselves at risk for the same long-term brain or nervous system injuries that are reported in older players," said Robert Heary, director of the Center for Spine Surgery and Mobility at Rutgers New Jersey Medical School. "Although concussions causing readily observable signs and symptoms are of great concern to physicians examining football players during and after games, the effects of other head trauma with fewer symptoms also can result in long-term damage."

The researchers monitored 20 members of a youth football team in New Jersey who wore helmets equipped with a system that tracked the number and severity of impacts that each player sustained during their 20-practice, seven-game season. A tackling coach taught players and coaches safe methods for blocking, defeating blocks and tackling that reduced head contact for both offensive and defensive players. During practices, the players wore Guardian Caps, which are helmets fitted with a padded cover that lessen the number of high-energy head impacts.

There were 817 recorded impacts during the season -- an average of 41 impacts per player and about 20 minutes of full contact per practice -- but no concussions.

"The use of Guardian Caps, safe tackling techniques and the age of participants may have contributed to the very low number of impacts recorded and the complete lack of injuries," said Heary.

Scientists at UC Davis have used CRISPR technology to genetically engineer rice with high levels of beta-carotene, the precursor of vitamin A. The technique they used provides a promising strategy for genetically improving rice and other crops. The study was published today in the journal Nature Communications.

Rice is a staple food crop for more than half the world's population. Golden Rice, a genetically engineered rice with high levels of beta-carotene, has been approved for consumption in more than five countries, including the Philippines, where vitamin A deficiency in children is widespread. Because of the social impact of Golden Rice, the researchers chose the high beta-carotene trait as an example.

Conventional plant genetic engineering uses a bacterium or a particle gun to transfer genes encoding desired traits into the plant genome. In this case, researchers would use a bacterium to take beta-carotene producing genes and transfer them into the rice genome. But those transgenes can integrate into random positions in the genome, which can result in reduced yields.

"Instead, we used CRISPR to precisely target those genes onto genomic safe harbors, or chromosomal regions that we know won't cause any adverse effects on the host organism," said first author Oliver Dong, a postdoctoral scholar in the UC Davis Department of Plant Pathology and Genome Center.

In addition, the researchers were able to precisely insert a very large fragment of DNA that does not contain marker genes. By contrast, conventional genetic engineering relies on the inclusion of marker genes in the inserted DNA fragment. These marker genes are retained when the plant is bred over generations, which can often trigger public concern and stringent regulations of the transgenic products before their entrance to the marketplace.

"Scientists have done targeted insertions before and without marker genes, but we haven't been able to do it with such big fragments of DNA," said Dong. "The larger the fragment of DNA, the more biological function or complex traits we can provide the plants."

Dong said this opens up the possibility that genes controlling multiple desirable traits, such as having high levels of beta-carotene as well as being disease-resistant or drought-tolerant, can be clustered at a single position within the genome. This can greatly reduce subsequent breeding efforts.

High blood pressure, or hypertension, affects everything from your arteries to your kidneys, from eyesight to sexual function. Among older adults, high blood pressure is also associated with cognitive decline as a result of interrupted blood flow to the brain, as well as strokes, heart attacks and impaired mobility.

A new Northwestern University-Tel Aviv University study has revealed that subjects who experienced relatively high blood pressure during young adulthood also experienced significant declines in cognitive function and gait in midlife (approximately 56 years old). The study cohort included about 200 young adults with an average age of 24 at the beginning of the study.

The research was led by Prof. Farzaneh A. Sorond and Dr. Simin Mahinrad of Northwestern University's Department of Neurology and Prof. Jeffrey Hausdorff of TAU's Sackler Faculty of Medicine, TAU's Sagol School of Neuroscience and Tel Aviv Medical Center's Center for the Study of Movement, Cognition, and Mobility at the Neurological Institute. The study was published in the American Heart Association's journal Circulation in March.

"We find that the deleterious effects of elevated blood pressure on brain structure and function begin in early adulthood. This demonstrates the need for preventive measures of high blood pressure even at this early age," explains Prof. Hausdorff. "We know that poor gait and cognitive function among older adults are associated with and predict multiple adverse health outcomes like cognitive decline, dementia, falls and death. Our study shows that the time to treat high blood pressure and to minimize future changes in gait and cognition is much earlier -- decades earlier -- than previously thought."

In addition, the study suggests that gait impairment may be an earlier hallmark of hypertensive brain injury than cognitive deficits.

For the study, the researchers assessed the blood pressure, gait and cognition of 191 participants from the Coronary Artery Risk Development in Young Adults study, a community-based cohort of young individuals followed over 30 years. In the last year of follow-up, gait was assessed using an instrumented gait mat; cognitive function was evaluated using neuropsychological tests; and the level of white matter intensity in the brain, a symptom of cardiovascular disease, was measured using MRIs. The impact of cumulative levels of high blood pressure was found to be independent of other vascular risk factors over the same 30-year period.

"Higher cumulative blood pressure was associated with slower walking speed, smaller step length and higher gait variability," Prof. Hausdorff says. "Higher cumulative blood pressure was also associated with lower cognitive performance in the executive, memory and global domains."

"Our takeaway is this: Even in young adults, blood pressure has significant implications, even at levels below the 'hypertension' threshold, and is important to assess and modify for future cognitive function and mobility," Prof. Hausdorff concludes.

STONY BROOK, NY, March 4, 2020 - A study using neuroimaging led by Stony Brook University professor and lead author Lilianne R. Mujica-Parodi, PhD, and published in PNAS, reveals that neurobiological changes associated with aging can be seen at a much younger age than would be expected, in the late 40s. However, the study also suggests that this process may be prevented or reversed based on dietary changes that involve minimizing the consumption of simple carbohydrates.

To better understand how diet influences brain aging, the research team focused on the presymptomatic period during which prevention may be most effective. In the article titled "Diet modulates brain network stability, a biomarker for brain aging, in young adults," they showed, using large-scale life span neuroimaging datasets, that functional communication between brain regions destabilizes with age, typically in the late 40's, and that destabilization correlates with poorer cognition and accelerates with insulin resistance. Targeted experiments then showed this biomarker for brain aging to be reliably modulated with consumption of different fuel sources: glucose decreases, and ketones increase, the stability of brain networks. This effect was replicated across both changes to total diet as well as after drinking a fuel-specific calorie-matched supplement.

"What we found with these experiments involves both bad and good news," said Mujica-Parodi, a Professor in the Department of Biomedical Engineering with joint appointments in the College of Engineering & Applied Sciences and Renaissance School of Medicine at Stony Brook University, and a faculty member in the Laufer Center for Physical and Quantitative Biology. "The bad news is that we see the first signs of brain aging much earlier than was previously thought. However, the good news is that we may be able to prevent or reverse these effects with diet, mitigating the impact of encroaching hypometabolism by exchanging glucose for ketones as fuel for neurons."

What the researchers discovered, using neuroimaging of the brain, is that quite early on there is breakdown of communication between brain regions ("network stability").

"We think that, as people get older, their brains start to lose the ability to metabolize glucose efficiently, causing neurons to slowly starve, and brain networks to destabilize," said Mujica-Parodi. "Thus, we tested whether giving the brain a more efficient fuel source, in the form of ketones, either by following a low-carb diet or drinking ketone supplements, could provide the brain with greater energy. Even in younger individuals, this added energy further stabilized brain networks."

To conduct their experiments, brain network stability was established as a biomarker for aging by using two large-scale brain neuroimaging (fMRI) datasets totaling nearly 1,000 individuals, ages 18 to 88. Destabilization of brain networks was associated with impaired cognition and was accelerated with Type 2 diabetes, an illness that blocks neurons' ability to effectively metabolize glucose. To identify the mechanism as being specific to energy availability, the researchers then held age constant and scanned an additional 42 adults under the age of 50 years with fMRI. This allowed them to observe directly the impact of glucose and ketones on each individual's brain.

The brain's response to diet was tested in two ways. The first was holistic, comparing brain network stability after participants had spent one week on a standard (unrestricted) vs. low carb (for example: meat or fish with salad, but no sugar, grains, rice, starchy vegetables) diet. In a standard diet, the primary fuel metabolized is glucose, whereas in a low-carb diet, the primary fuel metabolized is ketones. However, there might have been other differences between diets driving the observed effects. Therefore, to isolate glucose vs. ketones as the crucial difference between the diets, an independent set of participants was scanned before and after drinking a small dose of glucose on one day, and ketones on the other, where the two fuels were individually weight-dosed and calorically matched. The results replicated, showing that the differences between the diets could be attributed to the type of fuel they provide to the brain.

Additional findings from the study included the following: Effects of brain aging emerged at age 47, with most rapid degeneration occurring at age 60. Even in younger adults, under age 50, dietary ketosis (whether achieved after one week of dietary change or 30 minutes after drinking ketones) increased overall brain activity and stabilized functional networks. This is thought to be due to the fact that ketones provide greater energy to cells than glucose, even when the fuels are calorically matched. This benefit has previously been shown for the heart, but the current set of experiments provides the first evidence for equivalent effects in the brain.

"This effect matters because brain aging, and especially dementia, are associated with "hypometabolism," in which neurons gradually lose the ability to effectively use glucose as fuel. Therefore, if we can increase the amount of energy available to the brain by using a different fuel, the hope is that we can restore the brain to more youthful functioning. In collaboration with Dr. Eva Ratai at Massachusetts General Hospital, we're currently addressing this question, by now extending our studies to older populations," said Mujica-Parodi.

"Additional research with collaborators at Children's National, under the direction of Dr. Nathan Smith, focuses on discovering the precise mechanisms by which fuel impacts signaling between neurons. Finally, in collaboration with Dr. Ken Dill and Dr. Steven Skiena, at Stony Brook, we're working on building a comprehensive computational model that can incorporate our understanding of the biology, from individual neurons to whole brains to cognition, as it develops."

The research is currently funded under a new $2.5 million National Science Foundation BRAIN Initiative "Frontiers" grants (numbers (NSFECCS1533257 and NSFNCS-FR 1926781) awarded to Stony Brook, as well as by the W. M. Keck Foundation, which originally funded the team in 2017 with a $1 million seed grant designed to jump-start "pioneering discoveries in science, engineering, and medical research."