Researchers at Stockholm University have discovered that sleep affects how old you feel, with important health implications. The study is published in the scientific journal Proceedings of the Royal Society B.
Feeling young is not just a matter of perception: it is actually related to objective health outcomes. Previous studies have shown that feeling younger than one’s actual age is associated with longer, healthier lives. There is even support for subjective age to predict actual brain age, with those feeling younger having younger brains.
“Given that sleep is essential for brain function and overall well-being, we decided to test whether sleep holds any secrets to preserving a youthful sense of age,” says Leonie Balter, researcher at the Department of Psychology, Stockholm University.
In the first study, 429 individuals aged 18 to 70 were asked how old they felt, how many days in the past month they had not gotten enough sleep, and how sleepy they were.
It turned out that for each night with insufficient sleep in the past month, participants felt on average 0.23 years older.
In a second study, the researchers tested whether it was indeed the lack of sleep causing participants to feel older. They conducted an experimental sleep restriction study involving 186 participants aged 18 to 46. Participants restricted their sleep to four hours a night for two nights and another time slept sufficiently for two nights, with nine hours in bed each night.
After sleep restriction, participants felt on average 4.4 years older compared to when having enjoyed sufficient sleep.
The effects of sleep on subjective age appeared to be related to how sleepy they felt. Feeling extremely alert was related to feeling 4 years younger than one’s actual age, while extreme sleepiness was related to feeling 6 years older than one’s actual age.
“This means that going from feeling alert to sleepy added a striking 10 years to how old one felt,” says Leonie Balter, and states that the implications for our daily lives are clear:
“Safeguarding our sleep is crucial for maintaining a youthful feeling. This, in turn, may promote a more active lifestyle and encourage behaviours that promote health, as both feeling young and alert are important for our motivation to be active.”
Scientists have uncovered a key step in the wound healing process that becomes disabled in diseases like diabetes and ageing. Importantly, the research published in Nature reveals a molecule involved in the healing of tissues that leads to a drastic acceleration of wound closure, up to 2.5 times faster, and 1.6 times more muscle regeneration.
The immune system has a critical role in orchestrating tissue healing. As a result, regenerative strategies that control immune components have proved effective. This is particularly relevant when immune dysregulation that results from conditions such as diabetes or advanced age impairs tissue healing following injury. Nociceptive sensory neurons have a crucial role as immunoregulators and exert both protective and harmful effects depending on the context. However, how neuro–immune interactions affect tissue repair and regeneration following acute injury was unclear.
Lead researcher, Associate Professor Mikaël Martino, from Monash University’s Australian Regenerative Medicine Institute (ARMI) in Melbourne, Australia, said the discovery “could transform regenerative medicine, because it sheds light on the crucial role of sensory neurons in orchestrating the repair and regeneration of tissues, offering promising implications for improving patient outcomes.”
The cost of managing poorly healing wounds costs around $250 billion a year.
“In adults with diabetes alone – where poor blood flow can lead to quickly worsening wounds that are often very slow or impossible to heal – the lifetime risk of developing a diabetic foot ulcer (DFU), the most common diabetes-related wound, is 20 to 35 per cent and this number is rising with increased longevity and medical complexity of people with diabetes,” co-lead author, ARMI’s Dr Yen-Zhen Lu said.
Nociceptive sensory neurons, also called nociceptors, are the nerves in our body that sense pain.
These neurons alert us to potentially damaging stimuli in tissues by detecting dangers like tissue damage, inflammation, extremes in temperature, and pressure.
The researchers discovered that, during the healing process, sensory neuron endings grow into injured skin and muscle tissues, communicating with immune cells through a neuropeptide called calcitonin gene-related peptide (CGRP).
“Remarkably, this neuropeptide acts on immune cells to control them, facilitating tissue healing after injury,” Associate Professor Martino said.
Importantly they found that sensory neurons are crucial to the dissemination of CGRP because they showed that the selective removal of sensory neurons in mice reduce CGRP and significantly impairs skin wound healing and muscle regeneration following injury.
When the scientists administered an engineered version of CGRP to mice with neuropathy similar to that seen in diabetic patients, it led to rapid wound healing and muscle regeneration.
According to Associate Professor Martino, these findings hold significant promise for regenerative medicine, particularly for the treatment of poorly-healing tissues and chronic wounds.
“By harnessing neuro-immune interactions, the team aims to develop innovative therapies that address one of the root causes of impaired tissue healing, offering hope to millions,” he said.
“This study has uncovered significant implications for advancing our understanding of the tissue healing process after acute injury. Harnessing the potential of this neuro-immuno-regenerative axis opens new avenues for effective therapies, whether as standalone treatments or in combination with existing therapeutic approaches. “
Photo by Inzmam Khan: https://www.pexels.com/photo/man-in-black-shirt-and-gray-denim-pants-sitting-on-gray-padded-bench-1134204/
Antipsychotic medications for serious mental illness like schizophrenia or bipolar disorder often causes metabolic side effects such as insulin resistance and obesity, leading some patients to discontinue the treatment.
Now, a pilot study led by Stanford Medicine researchers has found that a ketogenic diet not only restores metabolic health in these patients as they continue their medications, but it further improves their psychiatric conditions. The results, published in Psychiatry Research, suggest that a dietary intervention can be a powerful aid in treating mental illness.
“It’s very promising and very encouraging that you can take back control of your illness in some way, aside from the usual standard of care,” said Shebani Sethi, MD, associate professor of psychiatry and behavioral sciences and the first author of the new paper.
The senior author of the paper is Laura Saslow, PhD, associate professor of health behavior and biological sciences at the University of Michigan.
Making the connection
Sethi, who is board certified in obesity and psychiatry, remembers when she first noticed the connection. As a medical student working in an obesity clinic, she saw a patient with treatment-resistant schizophrenia whose auditory hallucinations quieted on a ketogenic diet.
That prompted her to dig into the medical literature. There were only a few, decades-old case reports on using the ketogenic diet to treat schizophrenia, but there was a long track record of success in using ketogenic diets to treat epileptic seizures.
“The ketogenic diet has been proven to be effective for treatment-resistant epileptic seizures by reducing the excitability of neurons in the brain,” Sethi said. “We thought it would be worth exploring this treatment in psychiatric conditions.”
A few years later, Sethi coined the term metabolic psychiatry, a new field that approaches mental health from an energy conversion perspective.
Meat and vegetables
In the four-month pilot trial, Sethi’s team followed 21 adult participants who were diagnosed with schizophrenia or bipolar disorder, taking antipsychotic medications, and had a metabolic abnormality – such as weight gain, insulin resistance, hypertriglyceridaemia, dyslipidaemia or impaired glucose tolerance. The participants were instructed to follow a ketogenic diet, with approximately 10% of the calories from carbohydrates, 30% from protein and 60% from fat. They were not told to count calories.
“The focus of eating is on whole non-processed foods including protein and non-starchy vegetables, and not restricting fats,” said Sethi, who shared keto-friendly meal ideas with the participants. They were also given keto cookbooks and access to a health coach.
The research team tracked how well the participants followed the diet through weekly measures of blood ketone levels, which are produced when the body breaks down fat instead of glucose for energy. By the end of the trial, 14 patients had been fully adherent, six were semi-adherent and only one was non-adherent.
Physical and mental improvement
The participants underwent a variety of psychiatric and metabolic assessments throughout the trial.
Before the trial, 29% of the participants met the criteria for metabolic syndrome, defined as having at least three of five conditions: abdominal obesity, elevated triglycerides, low HDL cholesterol, elevated blood pressure and elevated fasting glucose levels. After four months on a ketogenic diet, none of the participants had metabolic syndrome.
On average, the participants lost 10% of their body weight; reduced their waist circumference by 11% percent; and had lower blood pressure, body mass index, triglycerides, blood sugar levels and insulin resistance.
“We’re seeing huge changes,” Sethi said. “Even if you’re on antipsychotic drugs, we can still reverse the obesity, the metabolic syndrome, the insulin resistance. I think that’s very encouraging for patients.”
The psychiatric benefits were also striking. On average, the participants improved 31% on a psychiatrist rating of mental illness known as the clinical global impressions scale, with three-quarters of the group showing clinically meaningful improvement. Overall, the participants also reported better sleep and greater life satisfaction.
“The participants reported improvements in their energy, sleep, mood and quality of life,” Sethi said. “They feel healthier and more hopeful.”
The researchers were impressed that most of the participants stuck with the diet. “We saw more benefit with the adherent group compared with the semi-adherent group, indicating a potential dose-response relationship,” Sethi said.
Alternative fuel for the brain
There is increasing evidence that psychiatric diseases such as schizophrenia and bipolar disorder stem from metabolic deficits in the brain, which affect the excitability of neurons, Sethi said. The researchers hypothesise that just as a ketogenic diet improves the rest of the body’s metabolism, it also improves the brain’s metabolism.
“Anything that improves metabolic health in general is probably going to improve brain health anyway,” Sethi said. “But the ketogenic diet can provide ketones as an alternative fuel to glucose for a brain with energy dysfunction.”
Likely there are multiple mechanisms at work, she added, and the main purpose of the small pilot trial is to help researchers detect signals that will guide the design of larger, more robust studies.
As a physician, Sethi cares for many patients with both serious mental illness and obesity or metabolic syndrome, but few studies have focused on this undertreated population. She is founder and director of the metabolic psychiatry clinic at Stanford Medicine.
“Many of my patients suffer from both illnesses, so my desire was to see if metabolic interventions could help them,” she said. “They are seeking more help. They are looking to just feel better.”
Replacing sugar with artificial and natural sweeteners in foods has been the subject of a great deal of controversy, due to conflicting reports about their potential to increase appetite. But according to a significant new study published in eBioMedicine, it does not in fact make people hungrier as is often held – and also helps to reduce blood sugar levels.
Previous studies into whether sugar replacement with sweeteners increase appetite have been carried out but did not provide robust evidence. But the researchers say that their study, which meets the gold standard level of proof in scientific investigation, provides very strong evidence that sweeteners and sweetness enhancers do not negatively impact appetite and are beneficial for reducing sugar intake.
The double blind randomised controlled trial found that consuming food containing sweeteners produced a similar reduction in appetite sensations and appetite-related hormone responses as sugary foods. Additionally, it was found to provide some benefits such as lowering blood sugar, which may be particularly important in people at risk of developing type 2 diabetes.
The trial was led by the University of Leeds in collaboration with the The Rhône-Alpes Research Center for Human Nutrition. It is the latest study to be published by the SWEET consortium of 29 European research, consumer and industry partners which is working to develop and review evidence on long term benefits and potential risks involved in switching over to sweeteners and sweetness enhancers in the context of public health and safety, obesity, and sustainability. It was funded by Horizon Europe.
Lead author Catherine Gibbons, Associate Professor in the University of Leeds’ School of Psychology, said: “Reducing sugar consumption has become a key public health target in the fight to reduce the rising burden of obesity-related metabolic diseases such as type 2 diabetes.
“Simply restricting sugar from foods without substitution may negatively impact its taste or increase sweet cravings, resulting in difficulties sticking to a low-sugar diet. Replacing sugars with sweeteners and sweetness enhancers in food products is one of the most widely used dietary and food manufacturing strategies to reduce sugar intake and improve the nutritional profile of commercial foods and beverages.”
Principal investigator Graham Finlayson, Professor of Psychobiology in the University of Leeds’ School of Psychology, said: “The use of sweeteners and sweetness enhancers has received a lot of negative attention, including high profile publications linking their consumption with impaired glycaemic response, toxicological damage to DNA and increased risk of heart attack and stroke. These reports contribute to the current befuddlement concerning the safety of sweeteners and sweetness enhancers among the general public and especially people at risk of metabolic diseases.
“Our study provides crucial evidence supporting the day-to-day use of sweeteners and sweetness enhancers for body weight and blood sugar control.”
Until now, virtually all studies of the effects of sweeteners and sweetness enhancers on appetite and glycaemia have been conducted using beverages as the vehicle. Few studies include volunteers with overweight or obesity and few have included volunteers of both sexes.
Most studies have only compared a single sweetener, mostly aspartame, with a control, and very few studies have examined the effect of repeated daily intake of a known sweetener or sweetness enhancer in the normal diet.
The study, which is the first of its kind, looked at the effects of consuming biscuits containing either sugar or two types of food sweetener: natural sugar substitute Stevia, or artificial sweetener Neotame on 53 adult men and women with overweight or obesity. Participants were all aged 18 to 60, with overweight or obesity.
The trial consisted of three two-week consumption periods, where participants consumed biscuits with either fruit filling containing sugar; natural sugar substitute Stevia, or artificial sweetener Neotame, each separated by a break of 14–21 days. Day 1 and day 14 of the consumption periods took place in the lab.
Participants were instructed to arrive in the lab after an overnight fast, a blood sample was taken to establish baseline levels of glucose, insulin and appetite-related hormones. They were also asked to rate their appetite and food preferences.
After consuming the biscuits, they were asked to rate how full they felt over several hours. Glucose and insulin levels were measured, as were ghrelin, glucagon-like peptide 1 and pancreatic polypeptide – hormones associated with the consumption of food.
The results from the two sweetener types showed no differences in appetite or endocrine responses compared to sugar, but insulin levels measured over two hours after eating were reduced, as were blood sugar levels.
Researchers have discovered a gene on the Y chromosome that contributes to the greater incidence of heart failure in men when the Y chromosome is lost to ageing.
Y chromosome loss in men occurs progressively throughout life and can be detected in approximately 40% of 70-year-old men. In 2022, Kenneth Walsh, PhD, at University of Virginia discovered that this loss can contribute to heart muscle scarring and lead to heart failure. (That finding was the first to directly link Y chromosome loss to a specific harm to men’s health; Y chromosome loss is increasingly thought to play a role in diseases ranging from Alzheimer’s to cancer.)
In an important follow-up finding published in Nature Cardiovascular Research, Walsh and his team have discovered how Y chromosome loss triggers changes in heart immune cells that make the cells more likely to cause scarring and heart failure.
Further, the researchers found they could reverse the harmful heart changes by giving lab mice a drug that targets the process of fibrosis that leads to the heart scarring, which could lead to a similar treatment for men.
“Our previous work identified that it was loss of the entire Y chromosome that contributed to heart disease in men,” said Walsh, the director of UVA’s Hematovascular Biology Center. “This new work identified a single gene on the Y chromosome that can account for the disease-promoting effects of Y chromosome loss.”
About Y chromosome loss
Unlike women, who have two X chromosomes, men have an X and a Y. For a long time, the genes found on the Y chromosome were not thought to play important roles in disease. Sex hormones, scientists thought, explained the differences in certain diseases in men and women. But Walsh’s groundbreaking work has helped change that perception. It also suggested an explanation for why heart failure is more common in men than women. (Cardiovascular disease, which includes heart failure, is the leading cause of death worldwide.)
Y chromosome loss occurs in only a small percentage of affected men’s cells. This results in what is called “mosaicism,” where genetically different cells occur within one individual. Researchers aren’t entirely sure why this partial Y chromosome loss occurs, but predominantly it strikes elderly men and men who smoke compared to those who don’t.
To better understand the effects of Y chromosome loss, Walsh and his team examined genes found on the Y chromosome to determine which might be important to heart scarring. One gene they looked at, Uty, helps control the operating instructions for immune cells called macrophages and monocytes, the scientists determined. When the Uty gene was disrupted, either individually or through Y chromosome loss, that triggered changes in the immune cells in lab mice. Suddenly, the macrophages were much more “pro-fibrotic,” or prone to scarring. This accelerated heart failure as well, the scientists found.
“The identification of a single gene on the Y chromosome provides information about a new druggable target to treat fibrotic diseases,” said Walsh, of UVA’s Division of Cardiovascular Medicine and Robert M. Berne Cardiovascular Research Center.
Walsh and his team were able to prevent the harmful changes in the mice’s macrophages by giving them a specially designed monoclonal antibody. This halted the harmful changes in the heart, suggesting the approach might, with further research, lead to a way to treat or avoid heart failure and other fibrotic diseases in men with Y chromosome loss.
“Currently, we are working with our clinician colleagues in the Division of Cardiovascular Medicine at UVA to assess whether loss of the Y chromosome in men is associated with greater scarring in the heart,” Walsh said. “This research will provide new avenues for understanding the causes of heart disease.”
Based on their findings, Walsh and his team believe that a small group of genes found on the Y chromosome may have big effects on a wide array of diseases. Their new work identifies mechanisms that may lead to this, and they are hopeful that further research will provide a much better understanding of unknown causes of sickness and death in men.
“This research further documents the utility of studying the genetics of mutations that are acquired after conception and accumulate throughout life,” Walsh said. “These mutations appear to be as important to health and lifespan as the mutations that are inherited from one’s parents. The study of these age-acquired mutations represents a new field of human genetics.”
