For hundreds of thousands of years, humans evolved to meet the physical and psychological demands of hunter-gatherer life, which required frequent movement, short bursts of intense stress and daily exposure to natural settings. Industrialization has altered these conditions within only a few centuries by adding noise, air and light pollution, microplastics, pesticides, continuous sensory input, artificial lighting, processed foods and long periods of sitting.

"In our ancestral environments, we were well adapted to deal with acute stress to evade or confront predators," says Colin Shaw, who leads the Human Evolutionary EcoPhysiology (HEEP) research group with Daniel Longman. "The lion would come around occasionally, and you had to be ready to defend yourself -- or run. The key is that the lion goes away again."

Modern stressors such as traffic, workplace pressure, social media and persistent noise activate the same biological pathways that once helped humans survive predators. Unlike the rapid resolution our ancestors experienced, these stressors rarely subside. "Our body reacts as though all these stressors were lions," Longman explains. "Whether it's a difficult discussion with your boss or traffic noise, your stress response system is still the same as if you were facing lion after lion. As a result, you have a very powerful response from your nervous system, but no recovery."

Industrialization and Its Impact on Health and Reproduction

In their review, Shaw and Longman evaluate research suggesting that the shift toward industrial and urban living is reducing human evolutionary fitness. Evolutionary success depends on both survival and reproduction, and the authors argue that both have been negatively influenced since industrialization began.

They highlight falling fertility rates across much of the world and increasing rates of inflammatory and autoimmune conditions as evidence that modern environments are placing stress on human biology. "There's a paradox where, on the one hand, we've created tremendous wealth, comfort and healthcare for a lot of people on the planet," Shaw says, "but on the other hand, some of these industrial achievements are having detrimental effects on our immune, cognitive, physical and reproductive functions."

One of the most studied examples is the steady decline in sperm count and sperm motility observed since the 1950s. Shaw notes that these trends appear to be linked to environmental exposures. "This is believed to be tied to pesticides and herbicides in food, but also to microplastics," he says.

Searching for Solutions That Support Human Wellbeing

Technological and environmental conditions continue to change far more rapidly than biological evolution can respond to. "Biological adaptation is very slow. Longer-term genetic adaptations are multigenerational -- tens to hundreds of thousands of years," Shaw says.

According to the researchers, this means the mismatch between human physiology and modern living conditions will not correct itself through natural evolutionary processes. Instead, they argue that societies must take active steps to reduce these pressures by strengthening connections to nature and creating healthier, more sustainable environments.

Addressing this mismatch requires both cultural and environmental changes. Shaw suggests treating nature as a crucial component of public health and protecting or restoring landscapes that resemble those in which humans originally evolved. He also advocates for rethinking city design to better align with human physiology and reduce harmful exposures.

"Our research can identify which stimuli most affect blood pressure, heart rate or immune function, for example, and pass that knowledge on to decision-makers," Shaw says. "We need to get our cities right -- and at the same time regenerate, value and spend more time in natural spaces."

The treatment, which is taken as a tablet, works in a completely different way from well-known GLP-1-based medications such as Ozempic that are given through injections. GLP-1 drugs influence hunger by altering communication between the gut and the brain, and they can cause side effects that include appetite loss, decreased muscle mass, and gastrointestinal discomfort.

Targeting Muscle Metabolism Rather Than Appetite

Instead of acting on hunger pathways, the new compound boosts metabolic activity directly within skeletal muscle. In animal studies, it improved blood sugar levels and body composition while avoiding the drawbacks commonly linked to today's GLP-1-based treatments.

A phase I clinical trial involving 48 healthy volunteers and 25 individuals with type 2 diabetes indicates that the treatment is also well tolerated in humans.

"Our results point to a future where we can improve metabolic health without losing muscle mass. Muscles are important in both type 2 diabetes and obesity, and muscle mass is also directly correlated with life expectancy," says Tore Bengtsson, professor at the Department of Molecular Bioscience, Wenner-Gren Institute, Stockholm University.

A New Type of β2 Agonist Designed for Safety

The active substance is based on a laboratory-developed molecule, a form of β2 agonist. This molecule activates key signaling pathways in a novel manner that benefits muscle function while avoiding the heart overstimulation typically associated with β2 agonists.

"This drug represents a completely new type of treatment and has the potential to be of great importance for patients with type 2 diabetes and obesity. Our substance appears to promote healthy weight loss and, in addition, patients do not have to take injections," says Shane C. Wright, assistant professor at the Department of Physiology and Pharmacology at Karolinska Institutet.

Potential as a Stand-Alone or Combination Therapy

Because this drug operates through a mechanism distinct from GLP-1 medications, it may be effective on its own or when paired with GLP-1 drugs.

"This makes them valuable both as a stand-alone treatment and in combination with GLP-1 drugs," says Shane C. Wright.

Next Steps and Research Collaboration

The next stage in development is a larger phase II clinical trial planned by Atrogi AB, the company leading the drug's advancement. This study will examine whether the positive effects observed in earlier research also appear in people living with type 2 diabetes or obesity.

The work represents a collaboration involving Professor Volker M. Lauschke and teams from Karolinska Institutet, Stockholm University, Uppsala University, the University of Copenhagen, Monash University, and the University of Queensland. Funding came from the Swedish Research Council, the Swedish Society for Medical Research, the Novo Nordisk Foundation, and additional sources.

Several authors are employed by or hold shares in Atrogi AB, which financed the clinical trial. Tore Bengtsson is the founder and chief scientific officer of Atrogi AB, which is continuing to develop the drug candidate, and he and a co-author have applied for patents related to the substances examined in the study. Additional company affiliations are detailed in the full publication.

"Many skin injuries end in scars, and in some people, it can lead to long-term cosmetic and even functional issues," said senior author Thomas Leung, MD, PhD, an associate professor of Dermatology at Penn. "Our findings suggest that rosemary extract, and specifically the antioxidant, carnosic acid, can shift the healing process from scarring to healthy skin regeneration. We don't have proven ways to consistently do that in humans."

A Viral Trend That Sparked a Scientific Question

Penn undergraduate student Jiayi Pang (left) and Penn PhD candidate Emmanuel Rapp Reyes (right) found that rosemary can help skin wounds heal without causing scars.

The idea for the project began on TikTok and Instagram. After noticing that many creators were promoting rosemary serums and rosemary-based products for better skin recovery, Pang and Rapp Reyes approached Leung to understand whether these claims had scientific merit. Their curiosity led them to begin a series of laboratory experiments.

"We hypothesized there was likely something real behind the hype because rosemary contains many antioxidants," said Pang, co-lead author of the study. "But we knew in order to really uncover its potential, we needed to prove its healing properties and uncover how exactly it was facilitating healing."

Testing Rosemary's Key Compound in the Lab

Working with mice, the research team created a cream made with carnosic acid, a naturally occurring antioxidant found primarily in rosemary. The cream sped up wound closure and helped regenerate structures such as hair follicles, oil glands, and cartilage. The scientists also found that the compound activated a skin nerve sensor known as TRPA1, which had previously been linked to the ability to heal without scars. When the cream was used on mice that lacked TRPA1, the treatment no longer produced the same regenerative effects.

"We also identified other herbs, such as thyme and oregano, that may activate TRPA1. But rosemary stood out for its potency and safety," said Rapp Reyes, co-lead author of the study. "Other natural ingredients, such as mustard oil, or the topical medication imiquimod are known to also stimulate the TRPA1 receptor, but unlike rosemary, those can cause irritation and inflammation."

Why Rosemary Works Only Where It Is Applied

The researchers discovered that rosemary's regenerative effect occurs only at the location where the carnosic acid cream is used. Applying the cream to areas of skin far from the injury did not lead to scar-free healing, emphasizing that its benefits are strictly local.

Potential for Future Wound Care Research

The Penn team advises people to speak with their healthcare providers before adding rosemary products to their skincare routine or creating homemade mixtures. Still, because rosemary is widely available and inexpensive, the researchers hope their findings encourage more exploration of its potential benefits in human wound care, especially for individuals prone to significant scarring.

"If rosemary is part of your skincare regimen and you think it's working, it likely is," said Leung. "I'm proud that the young scientists that led this research sought answers to questions in their everyday lives."