Science
What Nearly Brainless Rodents Know About Weight Loss and Hunger

Do we really have free will when it comes to eating? It’s a vexing question that is at the heart of why so many people find it so difficult to stick to a diet.
To get answers, one neuroscientist, Harvey J. Grill of the University of Pennsylvania, turned to rats and asked what would happen if he removed all of their brains except their brainstems. The brainstem controls basic functions like heart rate and breathing. But the animals could not smell, could not see, could not remember.
Would they know when they had consumed enough calories?
To find out, Dr. Grill dripped liquid food into their mouths.
“When they reached a stopping point, they allowed the food to drain out of their mouths,” he said.
Those studies, initiated decades ago, were a starting point for a body of research that has continually surprised scientists and driven home that how full animals feel has nothing to do with consciousness. The work has gained more relevance as scientists puzzle out how exactly the new drugs that cause weight loss, commonly called GLP-1s and including Ozempic, affect the brain’s eating-control systems.
The story that is emerging does not explain why some people get obese and others do not. Instead, it offers clues about what makes us start eating, and when we stop.
While most of the studies were in rodents, it defies belief to think that humans are somehow different, said Dr. Jeffrey Friedman, an obesity researcher at Rockefeller University in New York. Humans, he said, are subject to billions of years of evolution leading to elaborate neural pathways that control when to eat and when to stop eating.
As they have probed how eating is controlled, researchers learned that the brain is steadily getting signals that hint at how calorically dense a food is. There’s a certain amount of calories that the body needs, and these signals make sure the body gets them.
The process begins before a lab animal takes a single bite. Just the sight of food spurs neurons to anticipate whether a lot of calories will be packed into that food. The neurons respond more strongly to a food like peanut butter — loaded with calories — than to a low-calorie one like mouse chow.
The next control point occurs when the animal tastes the food: Neurons calculate the caloric density again from signals sent from the mouth to the brainstem.
Finally, when the food makes its way to the gut, a new set of signals to the brain lets the neurons again ascertain the caloric content.
And it is actually the calorie content that the gut assesses, as Zachary Knight, a neuroscientist at the University of California San Francisco, learned.
He saw this when he directly infused three types of food into the stomachs of mice. One infusion was of fatty food, another of carbohydrates and the third of protein. Each infusion had the same number of calories.
In each case, the message to the brain was the same: The neurons were signaling the amount of energy, in the form of calories, and not the source of the calories.
When the brain determines enough calories were consumed, neurons send a signal to stop eating.
Dr. Knight said these discoveries surprised him. He’d always thought that the signal to stop eating would be “a communication between the gut and the brain,” he said. There would be a sensation of having a full stomach and a deliberate decision to stop eating.
Using that reasoning, some dieters try to drink a big glass of water before a meal, or fill up on low-calorie foods, like celery.
But those tricks have not worked for most people because they don’t account for how the brain controls eating. In fact, Dr. Knight found that mice do not even send satiety signals to the brain when all they are getting is water.
It is true that people can decide to eat even when they are sated, or can decide not to eat when they are trying to lose weight. And, Dr. Grill said, in an intact brain — not just a brainstem — other areas of the brain also exert control.
But, Dr. Friedman said, in the end the brain’s controls typically override a person’s conscious decisions about whether they feel a need to eat. He said, by analogy, you can hold your breath — but only for so long. And you can suppress a cough — but only up to a point.
Scott Sternson, a neuroscientist with the University of California in San Diego and Howard Hughes Medical Institute, agreed.
“There is a very large proportion of appetite control that is automatic,” said Dr. Sternson, who is also a co-founder of a startup company, Penguin Bio, that is developing obesity treatments. People can decide to eat or not at a given moment. But, he added, maintaining that sort of control uses a lot of mental resources.
“Eventually, attention goes to other things and the automatic process will wind up dominating,” he said.
As they probed the brain’s eating-control systems, researchers were continually surprised.
They learned, for example, about the brain’s rapid response to just the sight of food.
Neuroscientists had found in mice a few thousand neurons in the hypothalamus, deep in the brain, that responded to hunger. But how are they regulated? They knew from previous studies that fasting turned these hunger neurons on and that the neurons were less active when an animal was well fed.
Their theory was that the neurons were responding to the body’s fat stores. When fat stores were low — as happens when an animal fasts, for example — levels of leptin, a hormone released from fat, also are low. That would turn the hunger neurons on. As an animal eats, its fat stores are replenished, leptin levels go up, and the neurons, it was assumed, would quiet down.
The whole system was thought to respond only slowly to the state of energy storage in the body.
But then three groups of researchers, independently led by Dr. Knight, Dr. Sternson and Mark Andermann of Beth Israel Deaconess Medical Center, examined the moment-to-moment activity of the hunger neurons.
They began with hungry mice. Their hunger neurons were firing rapidly, a sign the animals needed food.
The surprise happened when the investigators showed the animals food.
“Even before the first bite of food, the activity of those neurons shut off,” Dr. Knight said. “The neurons were making a prediction. The mouse looks at food. The mouse predicts how many calories it will eat.”
The more calorie-rich the food, the more neurons turn off.
“All three labs were shocked,” said Dr. Bradford B. Lowell, who worked with Dr. Andermann at Beth Israel Deaconess. “It was very unexpected.”
Dr. Lowell then asked what might happen if he deliberately turned off the hunger neurons even though the mice hadn’t had much to eat. Researchers can do this with genetic manipulations that mark neurons so they can turn them on and off with either a drug or with a blue light.
These mice would not eat for hours, even with food right in front of them.
Dr. Lowell and Dr. Sternson independently did the opposite experiment, turning the neurons on in mice that had just had a huge meal, the mouse equivalent of a Thanksgiving dinner. The animals were reclining, feeling stuffed.
But, said Dr. Andermann, who repeated the experiment, when they turned the hunger neurons on, “The mouse gets up and eats another 10 to 15 percent of its body weight.” He added, “The neurons are saying, ‘Just focus on food.’”
Researchers continue to be amazed by what they are finding — layers of controls in the brain that ensure eating is rigorously regulated. And hints of new ways to develop drugs to control eating.
One line of evidence was discovered by Amber Alhadeff, a neuroscientist at the Monell Chemical Senses Center and the University of Pennsylvania. She recently found two separate groups of neurons in the brainstem that respond to the GLP-1 obesity drugs.
One group of neurons signaled that the animals have had enough to eat. The other group caused the rodent equivalent of nausea. The current obesity drugs hit both groups of neurons, she reports, which may be a factor in the side effects many feel. She proposes that it might be possible to develop drugs that hit the satiety neurons but not the nausea ones.
Alexander Nectow, of Columbia University, has another surprise discovery. He identified a group of neurons in the brainstem that regulate how big a meal is desired, tracking each bite of food. “We don’t know how they do it,” he said.
“I’ve been studying this brainstem region for a decade and a half,” Dr. Nectow said, “but when we went and used all of our fancy tools, we found this population of neurons we had never studied.”
He’s now asking if the neurons could be targets for a class of weight loss drugs that could upstage the GLP-1s.
“That would be really amazing,” Dr. Nectow said.

Science
Just 5 minutes a day of these exercises can sharpen your brain as you age

Exercise has long been linked with stronger brains and reduced risk of dementia and other cognitive diseases. But new research suggests that older adults can significantly improve brain health with only a few minutes of daily movement.
Researchers from the University of South Australia and the U.S.-based AdventHealth Research Institute found that as few as five minutes of moderate-to-vigorous exercise a day correlated to significantly better cognitive performance. The study, published in the British journal Age & Ageing in early April, examined data from hundreds of people 65 to 80 years old.
Researchers found that “huff-and-puff” movements, like running or lap swimming, were associated with better brain functions including information processing, focusing and multitasking and short-term memory. They also found that even a few minutes of moderate exercise like walking improves brain functions.
“Our key finding was that moving from doing zero minutes or very little moderate-to-vigorous physical activity to doing just five minutes a day — that’s where the biggest gain in cognitive function was seen,” said the study’s lead author, Maddison Mellow, a research associate at the University of South Australia.
The researchers distinguished between moderate and vigorous exercise by applying a simple test: whether subjects could still manage to speak full sentences after moving around. Vigorous exercise makes that impossible, said Audrey Collins, a postdoctoral research scientist at AdventHealth Research Institute and the paper’s co-lead author.
The study observed 585 people, all in good health. Their physical activity was measured using accelerometers they wore on their wrists; the researchers tested cognitive functions using online and paper-based tests.
Worth noting: This study also found a “strong relationship” between spending little to no time doing moderate to vigorous activity and poorer cognitive performance, Mellow said. One slightly surprising finding, she added, was that the cognitive performance gains from exercise don’t extend to longer-term memory and visual-spatial functions like judging distances or sizes.
The study was novel in that it categorized how people divided their days into three behaviors: sleep, sedentary and active. And though getting enough quality sleep is important to brain health in midlife and beyond, the researchers said that when forced to choose between minutes spent sleeping and minutes spent exercising, reducing sleep time to spend more time moving resulted in better brain function.
“It didn’t really matter, in this sample, where time was coming from, whether from sleep, sedentary behavior or light intensity physical activity,” Mellow said. “So long as time was being increased in moderate vigorous activity, that’s where the benefits were being shown for cognitive outcomes.”
With that in mind, what are some moderate or vigorous bursts of exercise for older adults to do every day? We consulted experts to give you five accessible options.
1. Walking
Two experts I spoke with each said the easiest way to clock those five daily minutes for brain health is by walking.
“Walking is No. 1, because that’s the easiest,” said E. Todd Schroeder, professor of clinical physical therapy and the director of the Clinical Exercise Research Center at USC. Very sedentary older adults may want to start with simple flat-ground walking at their normal pace, Schroeder says.
If you’re already a steady, regular walker, kick up the pace to elevate your heart rate into that all-important moderate category.
“A brisk walk is considered to be moderate activity,” said Rob Musci, an assistant professor of health and human sciences at Loyola Marymount University. On a scale of 1 to 10, moderate exercise is what you would consider being in the 4 to 6 range, Musci said.
To achieve a real huff-and-puff workout, walking or hiking briskly uphill is excellent, Schroeder said, because it also necessarily requires walking back down hill.
“That interval-type training is good,” he said, “where your heart rate goes up for a time then comes back down.”
2. Swimming
Swimming is a terrific way to get a full-body workout and raise your heart rate.
“It’s easy on the joints,” Shroeder said. “Even if you struggle with the technique of swimming, you can put on fins and get some at least moderate exercise.”
3. Cycling
Cycling can be on a stationary bike or an outdoor bike, many of which are now battery-assisted, making pedaling up hills almost too easy. One reason I like old-fashioned outdoor bikes, sans batteries, is that they also train balance and require your brain to keep you safe.
4. Resistance training
Lifting weights is one of the best ways to maintain muscle strength as we age, Musci said. Try these simple exercises you can easily do at home in fewer than three minutes. They include:
- Tossing a weighted ball from one hand to another (try it standing on one leg)
- Squats holding a kettlebell, dumbbell, a bag of oranges or nothing at all
- Weighted chest presses in boat pose
5. Gardening and housework
Gardening can be a great way to engage core muscles, encourage flexibility and practice fine motor skills. Even basic house cleaning, like scrubbing a bathtub or mopping a floor, can qualify as moderate exercise.
“Anything that gets your heart going is what we’re looking for,” Musci said. “You hear about all these high-end interventions, fitness programs and boot camps, but in reality, it’s just movement.”
The most important thing, he said, is “just getting off the couch.”
Von Zielbauer is the creator of Aging With Strength on Substack.
Science
Biden is diagnosed with 'aggressive' form of prostate cancer

WASHINGTON — Former President Biden has been diagnosed with an “aggressive form” of prostate cancer, his office said Sunday, a devastating development after having dropped his bid for reelection last summer over widespread concerns over his age and health.
Biden’s personal office said he was examined last week after the president reported a series of concerning symptoms.
“Last week, President Joe Biden was seen for a new finding of a prostate nodule after experiencing increasing urinary symptoms. On Friday, he was diagnosed with prostate cancer, characterized by a Gleason score of 9 (Grade Group 5) with metastasis to the bone,” the office said in a statement.
“While this represents a more aggressive form of the disease, the cancer appears to be hormone-sensitive, which allows for effective management. The President and his family are reviewing treatment options with his physicians,” the statement added.
The former president, 82, had been making his first public appearances since leaving office in recent weeks, including a public address and a lengthy sit-down on ABC’s “The View,” and also hired a communications strategist to help burnish his legacy amid the publication of a series of books critically examining his time at the White House.
Biden has a tragic personal history with cancer, losing his son, Beau Biden, to glioblastoma in 2015, when he was serving as vice president. At that time, he launched the “cancer moonshot,” a government-wide push for improved cancer treatments that he relaunched during his presidency.
The spread of cancer to the bones will make Biden’s cancer difficult to cure. But its receptiveness to hormone treatments could help his medical team inhibit the cancer’s growth, at least temporarily.
Biden dropped out of the 2024 race in July under immense pressure from leadership in the Democratic Party after a disastrous debate with the Republican presidential nominee, Donald Trump, laid bare concerns over his age and acuity.
Within hours of dropping out of the race, Biden endorsed his vice president, Kamala Harris, to run in his place. She quickly coalesced the party around her nomination and avoided a primary battle, but lost to Trump in November.
In a post on X, Harris said she and her husband, Doug Emhoff, were saddened to learn of Biden’s diagnosis. “We are keeping him, Dr. Biden, and their entire family in our hearts and prayers during this time,” she wrote. “Joe is a fighter — and I know he will face this challenge with the same strength, resilience, and optimism that have always defined his life and leadership. We are hopeful for a full and speedy recovery.”
Last week on “The View,” Biden said he took responsibility for Trump’s return to power, because he was in office at the time. “I do, because, look, I was in charge and he won. So, you know, I take responsibility,” he said.
But he continued to reject criticisms that he and his team worked to conceal the effects of his age on his performance as president, saying he was not surprised by Harris’ loss and suggesting he still believes he could have beaten Trump had he stayed in the race.
“It wasn’t a slam dunk,” he said, referring to President Trump’s victory. “Let me put it this way. He’s had the worst 100 days any president’s ever had. And I would not say honesty has been his strong point.”
Trump expressed concern about Biden’s condition in a Truth Social post Sunday. “Melania and I are saddened to hear about Joe Biden’s recent medical diagnosis. We extend our warmest and best wishes to Jill and the family, and we wish Joe a fast and successful recovery,” he wrote.
California Gov. Gavin Newsom was among the many politicians from both parties who posted their warm wishes and prayers for the former president. “Our hearts are with President Biden and his entire family right now. A man of dignity, strength, and compassion like his deserves to live a long and beautiful life. Sending strength, healing and prayers his way,” Newsom wrote on X.
House Speaker Mike Johnson (R-La.) wrote on X: “This is certainly sad news, and the Johnson family will be joining the countless others who are praying for the former President in the wake of his diagnosis.”
Biden was spending the weekend in Delaware with family, an aide said.
Science
Nearly half of Pasadena Unified schools have contaminated soil, district finds

Eleven of the 23 Pasadena Unified School District schools, where students have been back on campus since January, have contaminated soil after the Eaton fire, the district found.
More than 40% of the schools had lead at levels exceeding the state’s health-based limits for residential soil, and more than 20% had arsenic levels beyond what L.A. County considers acceptable, according to the results released Wednesday.
The district found lead at more than three times the state’s allowable limit of 80 milligrams per kilogram of soil next to Blair High School’s tennis courts and more than double the limit at four elementary schools. Lead, when inhaled through dust or ingested from dirt-covered hands, can cause permanent brain and nerve damage in children, resulting in slowed development and behavioral issues.
Arsenic, a known carcinogen, was found at a concentration of 92 mg/kg at San Rafael Elementary School. The county has used 12 mg/kg as a reference level, based on an estimate of the highest naturally occurring arsenic levels in all of Southern California. The naturally occurring background level of arsenic in Altadena and Pasadena ranges from 4 to 10 mg/kg, according to a 2019 study by the U.S. Geological Survey.
There is no safe exposure level for arsenic or lead.
“I’m worried about her safety,” said Nicole Maccalla of her daughter, a sixth-grader at Octavia E. Butler Magnet, which is located less than a mile from the Eaton fire burn area. “I would really like to have assurances that she’s physically safe while she’s at school.”
Instead, what she got was a map of the school posted by the district showing lead levels 40% and 70% above the allowable limit in soil samples taken next to the school entrance and near the outdoor lunch tables, respectively.
“If, literally, you’ve got to walk by lead to walk up the steps to school, then how many kids are walking through that with their shoes and then walking into the classroom?” Maccalla said. “It’s not like these are inaccessible areas that are gated off.”
Maccalla made the hard decision to let her daughter return to school in January despite early fears — worrying that the trauma of changing schools directly after the fire would be too much.
Along with other concerned parents, Maccalla has been pushing for both soil and indoor testing for months at school board meetings. It was only after the L.A. County Department of Public Health announced in April that it had found 80% of properties had lead levels exceeding the state’s standards in some areas downwind that the district hired the environmental firm Verdantas to conduct testing at schools.
“The school board has been very resistant to any request for testing from parents,” she said. “The superintendent kept saying it’s safe.” The parents’ response: “Prove it.”
The district released test results for 33 properties it owns — some with district schools and children’s centers, others with charter and private schools, some rented to nonprofits — that were all largely unscathed by the fires. On the 22 properties with public schools, students have been back in the classroom since late January. The full results with maps for each school can be seen on the school district’s website.
The district stated on its website there was “no indication that students or staff were exposed to hazardous levels of fire-related substances in the soil,” noting that any contamination found was highly localized. (For example, although seven samples at Blair High School identified elevated lead levels, 21 samples did not.)
Health agencies also advised the district that soil covered with grass or cement was unlikely to pose a health risk.
In response to the results, the district stated it would restrict access to contaminated areas, complete follow-up sampling and work on remediation over the summer. No classroom instruction would be affected.
“We want to be abundantly clear: Safety is not negotiable,” Pasadena Unified School District Supt. Elizabeth Blanco said in a press release. “That’s why we’re moving forward with both urgency and care.”
For Maccalla, it’s too little too late. “I would like to know what their plan is for monitoring the health of the children, given you’ve got kids that have already been playing outside in that soil for four months straight,” she said. “So what’s their health crisis mitigation plan?”
The test results also found high levels of chromium — which, in some chemical configurations, is a carcinogen — on one campus. Another had high levels of a class of contaminants called polycyclic aromatic hydrocarbons, which can cause headaches, coughing, skin irritation and, over long periods of exposure, can come with an increased risk of cancer.
Three of the five properties with the district’s children’s centers also had elevated levels of heavy metals — two with lead, one with arsenic.
When Maccalla — who has spent much of her time after the fire volunteering with the community advocacy group Eaton Fire Residents United — first saw the map of her daughter’s school, she began to formulate a plan to rally volunteers to cover the contaminated areas with mulch and compost before school buses arrive again Monday morning. (That is an expert-approved remediation technique for fire-stricken soil.)
“If the district is not going to do it, the state’s not going to do it, our county’s not going to do it, our city’s not going to do it,” she said, “well, the citizens will. We absolutely will.”
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