Timing exercise according to a person’s natural propensity towards being a “morning lark” or an “night owl” could maximize its cardiovascular benefits, a randomized trial suggests.
Matching exercise according to individual body clocks maximized the sleep quality and several parameters of cardiovascular health of middle-aged adults with preclinical risk factors.
The findings highlight the added value of incorporating circadian biology into exercise plans to optimize health outcomes.
Reporting their findings in Open Heart, the researchers suggest that assessing for chronotype—the predisposition towards morningness or eveningness—should be considered when prescribing exercise for those at risk of cardiometabolic disease.
“Our study shows that when you exercise may be just as important as how you exercise,” researcher Arsalan Tariq, PhD, from the University of Lahore, explained to Inside Precision Medicine.
“Aligning workouts with an individual’s biological clock significantly amplifies cardiovascular and metabolic benefits, offering a simple way to personalize prevention and improve adherence.”
A person’s chronotype affects their sleeping patterns, hormonal secretion, and energy levels during the day through an internal timing mechanism.
This is regulated by the circadian clock in a system that influences various physiological processes including blood pressure, heart rate, glucose metabolism, and vascular function.
Tariq and team examined how timing exercise affected key indicators of cardiovascular health among at-risk middle-aged adults.
Participants were aged 40 to 60 years and had at least one cardiovascular risk factor, such as high blood pressure, overweight, or obesity. The group also included those with a family history of premature cardiovascular disease.
Participants were randomly assigned to exercise at a time that either matched or did not match their chronotype, between 8am and 11am or between 6pm and 9pm.
This consisted of five, 40-minute sessions per week of supervised moderate intensity aerobic exercise such as brisk or treadmill walking for 12 weeks.
Of the 134 participants who completed the 60 sessions, 70 were larks—34 of whom had exercise matched with chronotype—and 64 were owls, with 30 matched to chronotype.
Measurements taken at the start of the trial and three days after it finished showed particular improvements in sleep and systolic blood pressure among those matched with chronotype.
Sleep quality improved by 3.4 points in matched participants versus 1.2 in the unmatched on the Pittsburgh Sleep quality Index. Systolic blood pressure dropped by 10.8 mmHg compared with 5.5mmHg in matched versus unmatched groups, respectively.
Chronotype-aligned exercise also led to significantly greater improvements in diastolic blood pressure, heart rate variability, peak oxygen consumption, low-density lipoprotein, and fasting glucose compared with misaligned exercise.
“Personalized, time-matched exercise interventions may become a practical strategy in clinical and public health settings, potentially leading to better outcomes and improved engagement,” the researchers reported.
“Future research and guidelines may consider circadian factors as a core component of lifestyle-based disease prevention.”
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Studying mice, researchers at Toronto’s Sinai Health have found that semaglutide—the active ingredient in popular weight loss drugs that mimic the gut hormone GLP-1—acts directly on a subset of liver cells to improve organ function, and does so independently of weight loss. The finding challenges long-held assumptions about how GLP-1 medicines work in the liver and could reshape how physicians treat metabolic liver disease.
For years, the liver benefits of semaglutide have puzzled scientists. “Glucagon-like peptide-1 (GLP-1) medicines improve metabolic liver disease through weight-loss-dependent and -independent actions,” the authors wrote. The drug was known to lower blood sugar and promote weight loss, but patients’ livers were improving in ways that those effects alone could not explain. And as the authors further noted, “The therapeutic scope of GLP-1 medicines extends beyond glycemic control and weight loss, with benefits evident in people with atherosclerotic heart disease, heart failure with preserved ejection fraction (HFpEF), peripheral artery disease, diabetic kidney disease, knee osteoarthritis, and obstructive sleep apnea (OSA).” However, as the team further pointed out, “… the mechanisms by which GLP-1 medicines improve organ dysfunction remain incompletely understood.”
Drucker has been at the forefront of GLP-1 research since the 1980s when his pioneering discoveries helped lay the groundwork for the development of GLP-1 medicines. After transforming treatment of type 2 diabetes and obesity, semaglutide and other GLP-1 medicines have been approved for other conditions including MASH (metabolic dysfunction-associated steatohepatitis). MASH is a severe form of fatty liver disease in which fat build-up, inflammation, and tissue scarring can lead to cirrhosis and liver failure. It affects about 25% Canadian adults and because it is closely linked with obesity and type 2 diabetes, treatment typically includes lifestyle interventions to reduce weight. “The approval of semaglutide for MASH highlights the importance of understanding the hepatoprotective mechanisms of GLP-1 action,” the investigators stated.
Drucker and colleagues have now found that semaglutide acts directly on the liver to reduce inflammation and scarring and improve organ function in a way that is independent of weight loss. Their finding overturns a prevailing assumption in the field that liver cells do not carry the receptor that semaglutide binds to, meaning the drug had no direct route to the organ.
Postdoctoral researcher Maria Gonzalez-Rellan, PhD, spearheaded the work that combined sophisticated mouse models of MASH with deep molecular analyses of liver cells. Her work identified two cell types carrying semaglutide receptors: liver sinusoidal endothelial cells (LSECs) and immune T cells. Although LSECs account for only about 3% of liver cell volume, they proved to be the key driver of semaglutide’s liver benefits.
A pioneer in GLP-1 biology, Daniel Drucker, MD, has dedicated his career to understanding how the GLP-1 hormone, and the therapies derived from it, function in the body. His early discovery that GLP-1 stimulates insulin secretion in a glucose-dependent manner paved the way for today’s widely popular medications for type 2 diabetes and obesity. Drucker’s ongoing research continues to shine light on the less understood aspects of GLP-1 biology including its effects on the liver and in regulating inflammation. [Colin Dewar, Sinai Health]
LSECs line the tiniest blood vessels in the liver and are studded with pores that allow them to act as a molecular sieve, filtering substances passing between the liver and the bloodstream. Gonzalez-Rellan showed that semaglutide reversed MASH in mice that lacked the brain receptors controlling appetite, demonstrating that weight loss is not required for liver benefits. “Unexpectedly. semaglutide improves hepatic inflammation, fibrosis, and immune remodeling through actions on Glp1r+ pericentral liver sinusoidal ECs (LSECs) independent of changes in body weight (BW),” the team reported. “… we leveraged a unique model of GLP-1R deficiency, Glp1rWnt1-/- mice, which are resistant to GLP-1RA-induced weight loss. Remarkably, semaglutide markedly improved hepatic steatosis, fibrosis, and immune remodeling in the absence of weight reduction.”
In a further test, mice lacking LSEC receptors showed no liver improvement on semaglutide even after losing 20% of their body weight. Detailed molecular analyses of liver cell types showed that semaglutide shifts gene activity in LSCEs, prompting them to release anti-inflammatory molecules that act on the broader liver environment, pushing it toward a state more closely resembling a healthy, disease-free liver. “Together, the data using mouse models of MASH reveal an EC-specific, weight-loss-independent, semaglutide-regulated, GLP-1R-dependent intrahepatic network for improving liver health,” the scientists said.
“It turns out that the receptor responsible for these benefits is in a very specialized population of liver cells,” commented Drucker, who is also a professor of medicine at the University of Toronto. “And this receptor orchestrates the production of molecules that talk to many different types of liver cells to calm down the inflammatory environment that is the problem in metabolic disease.”
The findings carry practical implications. GLP-1 medicines have become widely prescribed, yet their mechanism of action in the body, beyond appetite suppression and blood sugar control, have remained incompletely understood. Knowing that semaglutide improves liver health independently of weight loss could influence prescribing decisions. “We’ve seen in clinical trials that patients who lose very little weight see the same reductions in liver inflammation, scarring and enzyme levels as those who lose a great deal of weight. Now we know why,” Drucker pointed out. In their paper the team concluded “Hence, semaglutide produces a broad proteomic remodeling of the liver, enabling restoration of metabolic homeostasis and suppression of fibrogenic and inflammatory programs. The strong concordance between single-cell transcriptional changes, bulk tissue proteomics, and biomarker signatures underscores the breadth of GLP-1R-mediated hepatic reprogramming.”
Physicians may choose lower doses that avoid the side effects associated with the higher doses needed for significant weight loss, potentially also lowering costs for patients, Drucker suggested adding “We’re not saying weight loss isn’t important because many things improve when patients lose weight. But we now know that weight shouldn’t be the only measure of success, because GLP-1 medicines will improve liver health whether or not the patient loses weight.”
Balkhy is the director of the World Health Organization’s Eastern Mediterranean region, an entity that includes several of the countries caught up in the conflict between the United States, Israel, and Iran. The problems it has been posing — not just to individuals’ health and safety but to entire health care systems — are robbing her of sleep.
From designing drugs with a simple text prompt to running experiments guided by extended reality, a new wave of agentic AI is transforming the modern lab. Our editors discuss the latest autonomous systems accelerating biological discovery. In business deals, Gilead Sciences has acquired Tubulis in a transaction worth up to $5 billion, strengthening the buyer’s position in antibody–drug conjugates for cancer. Correspondingly, Eli Lilly and Biogen are each making billion-dollar-plus bets, acquiring Centessa, a sleep disorder drug developer, and Apellis, known for its work in immunology and rare diseases. Our episode rounds out by unpacking the dynamic obesity drug market, where intensifying competition from Novo Nordisk’s Wegovy pill is prompting Lilly to temper the 2026 sales outlook for its oral obesity drug, Foundayo.
Listed below are links to the GEN stories referenced in this episode of Touching Base:
BackgroundPostherpetic neuralgia (PHN) is often accompanied by depression, creating a vicious cycle that exacerbates symptoms and contributes to suboptimal treatment outcomes, even with interventional therapies. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in alleviating both pain and mood disturbances. However, its efficacy in enhancing prognosis when used alongside interventional neuromodulation therapy for PHN accompanied by depression remains inadequately explored and requires further investigation.ObjectiveThis study aims to generate preliminary evidence on the efficacy and safety of rTMS in enhancing prognosis and alleviating pain in patients with PHN and mild to moderate depression undergoing interventional neuromodulation therapy.MethodsThis study is a single-center, randomized, double-blind, placebo-controlled trial involving 174 adult patients with PHN. Participants will be randomly assigned, stratified by interventional neuromodulation therapy, to either the rTMS group (n=87) or the control group (n=87). Both groups will undergo either 10 Hz rTMS or sham stimulation for five consecutive days. The primary outcome is the incidence of poor prognosis at 3 months post-discharge. Secondary outcomes include the incidence of poor prognosis at 6 months post-discharge; Visual Analog Scale (VAS) sleep scores; short-form McGill Pain Questionnaire (SF-MPQ) scores; Self-Rating Depression Scale (SDS) scores; patient satisfaction; Pain Disability Index (PDI) scores; Multidimensional Fatigue Inventory-20 (MFI-20) scores; pregabalin oral doses; and the need for tramadol or antidepressants. Safety outcomes will include assessments of headache, pain at the stimulation site, neck pain, insomnia, muscle soreness, dizziness, nausea, tinnitus, irritability, tachycardia (heart rate > 100 bpm), and epilepsy. Data will be analyzed using a modified intention-to-treat approach.DiscussionThis study aims to provide preliminary evidence on the efficacy and safety of 10 Hz rTMS in improving prognosis and alleviating pain in PHN patients with mild to moderate depression undergoing interventional pain management.Trial registrationhttps://www.chictr.org.cn/bin/project/edit?pid=261070, identifier ChiCTR2500096978.
Post-stroke insomnia (PSI) is a critical biological barrier to neurorehabilitation afflicting over half of all stroke survivors. Traditional sedatives often force clinicians into a therapeutic dilemma between sleep efficacy and cognitive suppression. The microbiota-gut-brain (MGB) axis has recently emerged as a transformative target to resolve this impasse. Acute stroke triggers profound autonomic dysfunction, causing immediate intestinal barrier collapse. This “leaky gut” facilitates the systemic translocation of lipopolysaccharides (LPS) and activates the NLRP3 inflammasome. The resulting inflammatory storm hijacks central tryptophan metabolism via the indoleamine 2,3-dioxygenase (IDO) enzyme. This “tryptophan steal” diverts serotonin precursors toward neurotoxic kynurenine pathways, driving severe cortical hyperarousal. Sleep fragmentation then prevents the glymphatic system from clearing metabolic waste, further exacerbating neuroinflammation. To break this vicious cycle of neurotoxicity, we propose a phase-dependent therapeutic framework. During the highly vulnerable acute phase, interventions must prioritize gut barrier protection using postbiotics to mitigate infection risks under CNS injury-induced immunodepression (CIDS), often discussed as stroke-induced immunosuppression. As patients enter the chronic phase, therapy shifts toward metabolic restoration using live therapeutics, such as washed microbiota transplantation (WMT) and next-generation psychobiotics like Akkermansia muciniphila. Targeting the MGB axis offers a mechanism-based strategy to achieve precision sleep medicine, restoring the biological foundation necessary for optimal neuroplasticity and recovery.
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<![CDATA[Stroke recovery lasts years; learn why fatigue, sleep, hormones and cognition demand ongoing rehab beyond 90 days—and how progress can continue.]]>
In a new study published in Nature Communications titled, “Modelling synaptic dysfunction in childhood dementia using human iPSC-derived cortical networks,” researchers from Flinders University in Adelaide have uncovered how hyperactive and dysregulated synaptic circuits emerge in the brain tissue of children impacted by Sanfilippo syndrome, a common form of childhood dementia.
In Australia, an estimated 1400 children currently live with childhood dementia, with hundreds of thousands of cases worldwide. Sanfilippo syndrome is a rare genetic condition that causes fatal brain damage. Children typically reach early developmental milestones before rapidly losing cognitive skills, speech, and mobility. Early symptoms often include hyperactivity and sleep disturbance.
Alterations in synaptic communication play key roles in neurodegenerative disease progression and cognitive decline. Yet few studies have explored how excitation and inhibition synaptic imbalances contribute to pediatric neurodegenerative disorders.
Cedric Bardy, PhD, professor and head of the Laboratory for Human Neurophysiology and Genetics at the South Australian Health, describes the study findings as “significant progress.”Chronic overactivity in the brain appears to be a fundamental mechanism contributing to cognitive deterioration in children with Sanfilippo syndrome.
Using human stem cell-derived cortical neurons and electrophysiology, the team demonstrated that excitatory synapses in the neurons of affected children become abnormally active during early brain development.
While these neurons initially developed and functioned normally, they became increasingly overactive over time. Brain cell networks showed bursts of intense, highly synchronized electrical activity as they matured, mirroring the hyperactivity and neurological symptoms seen in children with the condition.
“This hyperactivity offers a clear biological explanation for early behavioral changes, and it brings us closer to understanding the complex mechanisms contributing to childhood dementia,” said Bardy.
Results also demonstrated that these neurons are vulnerable to stress. When exposed to mild nutrient deprivation, excitatory synaptic abnormalities increased, suggesting that common illnesses or physiological stressors may accelerate neurological decline.
“Our research shows that disrupted synaptic communication is not simply a byproduct of degeneration. It is an early driver of the disease,” Bardy says.
Childhood Dementia Initiative CEO and founder, Megan Maack, is a co-author of the study and has been involved in guiding the project since its inception.
“This research is significant not just for Sanfilippo syndrome, but for the field of childhood dementia as a whole,” said Maack. “By identifying the precise cellular mechanisms driving the disease, we are moving towards a personalized medicine approach—the kind of targeted treatment strategy that has transformed outcomes for children with cancer.”
Researchers are now evaluating whether drugs that are already on the market for use in other conditions could be repurposed for childhood dementia. Bardy says the team has already demonstrated that these synaptic imbalances can be corrected with certain medications in the laboratory, indicating that they represent a genuine therapeutic target.
![A pioneer in GLP-1 biology Dr. Daniel Drucker has dedicated his career to understanding how the GLP-1 hormone, and the therapies derived from it, function in the body. His early discovery that GLP-1 stimulates insulin secretion in a glucose-dependent manner paved the way for today's widely popular medications for type 2 diabetes and obesity. Dr. Drucker's ongoing research continues to shine light on the less understood aspects of GLP-1 biology including its effects on the liver and in regulating inflammation. [Colin Dewar, Sinai Health]](https://www.genengnews.com/wp-content/uploads/2026/04/Low-Res_Drucker_LTRI_Colin_Dewar-225x300.jpeg)