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Discoveries

IN THIS ISSUE

Cell Metabolism
10/2022

Time-restricted eating improves health of firefighters

Professor Satchin Panda and team, in collaboration with UC San Diego and the San Diego Fire-Rescue Department, conducted a clinical trial and found that time-restricted eating improved measures of health and wellbeing in firefighters. Eating during a 10-hour window decreased firefighters’ “bad” cholesterol and alcohol intake, as well as improved their mental health, blood sugar, and blood pressure. The researchers also discovered that time-restricted eating may provide even greater benefits for those at risk for cardiometabolic disease and other chronic diseases.

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Nature Chemical Biology
10/2022

Anti-inflammatory molecules that decline in the aging brain

Aging involves complicated plot twists and a large cast of characters: inflammation, stress, metabolic changes, and many others. Professor Alan Saghatelian, Senior Research Associate Dan Tan, and colleagues, in collaboration with UC San Diego, revealed another factor implicated in the aging process—a class of lipids called SGDGs, which decline in the brain with age and may have anti-inflammatory effects. The finding could have implications for neurodegenerative disorders and other conditions that involve increased brain inflammation.

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Neuron
10/2022

Growing motor neurons guided by “love-hate relationship” with blood vessels

When neurons involved in movement—called motor neurons—form, they must build connections that reach from the brain, brainstem, or spinal cord all the way to the toes. Now, Professor Samuel Pfaff, his team, and colleagues at the San Raffaele Scientific Institute in Italy provide a new understanding of how a “push-pull” relationship with blood vessels—in which growing neurons both attract blood vessels to them while also pushing them out of the way—guides the growth and development of motor neurons. Their discovery has implications for diseases in which motor neuron connections are destroyed, such as amyotrophic lateral sclerosis (ALS) or spinal muscular atrophy (SMA).

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Nature Neuroscience
12/2022

The brain’s ability to perceive space expands like the universe

As we move about in our daily lives, we tend to think that we navigate space in a linear way—but our brain does not always act in a linear manner. Professor Tatyana Sharpee, graduate student Huanqiu Zhang, and colleagues discovered that time spent exploring an environment causes neural representations to grow in surprising ways. Neurons in the hippocampus, essential for spatial navigation, memory, and planning, represent space in a manner that conforms to a nonlinear hyperbolic geometry—a three-dimensional expanse that grows outward exponentially (like the interior of an expanding hourglass). This discovery provides valuable methods for analyzing data on neurocognitive disorders involving learning and memory, such as Alzheimer’s disease.

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PNAS
12/2022

Salk scientists develop compound that reverses gut inflammation in mice

A drug developed by Salk Institute researchers acts like a master reset switch in the intestines. The compound, called FexD, was previously found to lower cholesterol, burn fat, and ward off colorectal cancer in mice. Now, co-corresponding authors Professor Ronald Evans and Senior Staff Scientist Michael Downes and colleagues have found that FexD can also prevent and reverse intestinal inflammation in mouse models of inflammatory bowel disease, an umbrella diagnosis that includes both Crohn’s disease and ulcerative colitis. Their research provides new, important information about the complex link between gut health and inflammation that has the potential to lead to an inflammatory bowel disease therapeutic.

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Cell Stem Cell
12/2022

Deteriorating neurons are source of human brain inflammation in Alzheimer’s disease

Despite decades of research, Alzheimer’s disease remains a debilitating and eventually fatal dementia with no effective treatment options. Now, Professor Rusty Gage, graduate student Joseph Herdy, and colleagues have found that neurons from people with Alzheimer’s disease show deterioration and undergo a late-life stress process, called senescence. These neurons have a loss of functional activity, impaired metabolism, and increased brain inflammation. Additionally, the team discovered that targeting these deteriorating neurons with therapeutics could be an effective strategy for preventing or treating Alzheimer’s disease.

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Nature
12/2022

Genetic changes that turn “on” cancer genes

In addition to communicating with other cells, cells also have an internal monologue—one that occurs as they regulate gene activity. Assistant Professor Jesse Dixon, Postdoctoral Fellow Zhichao Xu, and colleagues have zeroed in on the specific mechanisms that activate oncogenes—altered genes that can cause normal cells to become cancerous. Cancer can be caused by genetic mutations, yet the impact of specific types, such as structural variants that break and rejoin DNA, can vary widely. The researchers found that genetic mutation activity depends on the distance between a particular gene and the sequences that regulate the gene, as well as on the activity level of the regulatory genetic sequences involved. The work advances the ability to predict and interpret which genetic mutations found in cancer genomes are causing the disease.

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Cell Metabolism
01/2023

Time-restricted eating reshapes gene expression throughout the body

Numerous studies have shown health benefits from time-restricted eating, making practices like intermittent fasting a hot topic in the wellness industry. Now, Professor Satchin Panda and team show how time-restricted eating influences gene expression across more than 22 regions of the body and brain in mice. The team found a system-wide, molecular impact of time-restricted eating in mice, and noted that the time-restricted eating aligned the circadian rhythms of multiple organs in the body. The findings have implications for a wide range of health conditions, such as diabetes, heart disease, and cancer.

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Nature
01/2023

Supplementation with amino acid serine eases neuropathy in diabetic mice

Approximately half of people with type 1 or type 2 diabetes experience peripheral neuropathy—weakness, numbness, and pain, primarily in the hands and feet. Now, working in mice, Professor Christian Metallo, Postdoctoral Fellow Michal Handzlik, and colleagues have identified another factor contributing to diabetes-associated peripheral neuropathy: altered amino acid metabolism. The researchers were able to alleviate neuropathy symptoms in diabetic mice by supplementing their diets with the amino acid serine. The findings may provide a new way to identify people at high risk for peripheral neuropathy, as well as a potential treatment option.

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Cell Metabolism
01/2023

Microprotein increases appetite in mice

Salk scientists study how biological processes, like metabolism, can be used to improve cancer treatment outcomes. Tiny proteins, called microproteins, have long been overlooked in obesity and metabolic disease research. Now, Professor Alan Saghatelian and colleagues at UC Irvine have discovered that both brown and white fat are filled with thousands of previously unknown microproteins. They also showed that administering one of these microproteins, called Gm8773, can increase appetite in mice. Their findings may lead to the development of a therapeutic to help people gain weight in certain disease situations, such as during chemotherapy for cancer.

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Nature
02/2023

Three hallmarks of aging work together to prevent cancer

Communication is key for warding off cancerous cells. As we age, the end caps of our chromosomes, called telomeres, gradually shorten. Professors Jan Karlseder and Gerald Shadel and colleagues have discovered that when telomeres become very short, they communicate with mitochondria, the cell’s powerhouses. This communication triggers a complex set of signaling pathways and initiates an inflammatory response that destroys cells that could otherwise become cancerous. These findings could lead to new ways of preventing and treating cancer, as well as designing better interventions to offset the harmful consequences of aging.

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