New pill can mimic the health benefits of exercise

In a breakthrough development, scientists are on the brink of creating a pill that could simulate the health benefits traditionally obtained from exercise. This novel approach is aimed at combating muscle deterioration and various medical ailments, including heart disease and neurodegenerative disorders.

The research will be presented by experts from the Washington University in St. Louis (WUSTL) during the American Chemical Society (ACS) Spring 2024 meeting. This hybrid event, featuring nearly 12,000 scientific presentations, is held both virtually and in-person from March 17-21.

Irreplaceable value of physical activity 

Lead researcher Bahaa Elgendy, a professor of anesthesiology at WUSTL, emphasized the irreplaceable value of physical activity but acknowledged the necessity for alternatives in certain situations. 

“We cannot replace exercise; exercise is important on all levels. If I can exercise, I should go ahead and get the physical activity. But there are so many cases in which a substitute is needed [for example in older people of those suffering from various diseases.]”

Metabolic shifts seen after physical activity 

The team’s discovery centers on compounds that initiate the metabolic shifts seen after physical exertion, specifically targeting estrogen-related receptors (ERRs) which are pivotal in muscle cell metabolism, growth, and performance enhancement. 

After a decade of research, they have developed a promising compound, SLU-PP-332, which activates all three forms of ERR, including ERRα, a key regulator of exercise-induced stress adaptation in muscle. Initial experiments with mice demonstrated that this compound not only increased fatigue-resistant muscle fibers but also significantly boosted endurance.

Improved simulation of exercise effects 

To create SLU-PP-332, the scientists meticulously analyzed the structure of ERRs and their activation mechanism. Building on this foundation, they have engineered new molecules that forge stronger bonds with these receptors, potentially offering enhanced effects compared to SLU-PP-332, alongside improved stability and reduced toxicity risk.

The effectiveness of SLU-PP-332 and its successors was measured by examining RNA levels, reflecting gene expression, in rat heart muscle cells. The results indicated a more pronounced simulation of exercise effects with the new compounds.

Targeting estrogen-related receptors

Preliminary research with SLU-PP-332 shows promise in treating obesity, heart failure, and age-related kidney function decline by targeting ERRs. 

Additionally, ERR activity might mitigate brain damage associated with Alzheimer’s and other neurodegenerative diseases. Although SLU-PP-332 does not cross into the brain, several new compounds have been designed with this capability in mind.

Physiological advantages of physical activity

Elgendy expressed optimism about the potential of activating ERRs to produce a range of health benefits. The research team, in collaboration with Pelagos Pharmaceuticals – a startup they co-founded – is planning to further test these compounds in animal models and explore their application in treating neurodegenerative disorders. 

This innovative endeavor could pave the way for revolutionary treatments that offer the physiological advantages of exercise without the need for physical exertion.

Health benefits of exercise

Exercise offers a wide array of health benefits that positively impact both the body and mind. Here’s a summary of the key benefits:

Cardiovascular health

Regular physical activity strengthens the heart and improves circulation, which can reduce the risk of heart disease and stroke.

Weight management

Exercise helps in maintaining a healthy weight by burning calories and increasing metabolism.

Strengthens muscles and bones

Activities like weightlifting can stimulate muscle building when paired with adequate protein intake. Exercise also helps in building bone density and reducing the risk of osteoporosis as you age.

Mental health

Physical activity is known to reduce symptoms of depression and anxiety. It releases endorphins, which create feelings of happiness and euphoria.

Cognitive function

Regular physical activity can help keep your thinking, learning, and judgment skills sharp as you age. It can also reduce the risk of developing conditions such as Alzheimer’s disease.

Improves sleep

Exercise can help you fall asleep faster and deepen your sleep, provided it’s not too close to bedtime.

Increases lifespan

Regular physical activity is associated with a longer lifespan. Even moderate amounts of exercise can make a significant difference.

Immune system

Regular, moderate exercise can boost your immune system and help fight off infections.

Mobility and flexibility

Exercise helps maintain physical function and can prevent the loss of mobility and flexibility with aging.

Quality of life

Regular physical activity can improve your overall quality of life by enhancing your ability to perform daily activities, increasing your energy levels, and improving your overall mood.

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