Exercise Protein Reverses Muscle and Bone Aging

South Korean researchers have identified a key protein that explains why exercise becomes less effective with age and offers new hope for treating age-related muscle and bone decline.

The protein, called CLCF1, decreases naturally as we age but surges during exercise in younger people.

The study, published in Nature Communications, demonstrates how this single molecule coordinates the beneficial effects of physical activity on both muscle strength and bone density. Scientists found that restoring CLCF1 levels in aged mice dramatically improved their physical performance and bone health.

The Age-Exercise Disconnect

Exercise produces different results in young versus older adults, but the biological reasons remained unclear until now. Dr. Yong Ryoul Yang from the Korea Research Institute of Bioscience and Biotechnology led a team that discovered CLCF1 levels spike immediately after exercise in young people, while older adults require 12 weeks of continuous training to see similar increases.

“This research provides a biological basis for why exercise becomes less effective with age, and it lays the groundwork for developing new therapeutic strategies for healthy aging,” Yang explained.

The protein acts as a molecular messenger, released by muscles during physical activity to enhance both muscle function and bone formation while suppressing bone breakdown.

Remarkable Recovery Results

When researchers administered CLCF1 to elderly mice, the results were striking:

• Grip strength increased significantly within two weeks
• Running endurance improved by up to 70%
• Muscle fiber size expanded without affecting fiber number
• Bone density increased while bone-destroying cells decreased
• Glucose metabolism improved substantially

Multiple Mechanisms of Action

The research revealed that CLCF1 works through several pathways simultaneously. In muscles, it enhances glucose uptake and powers cellular energy factories called mitochondria. The protein also activates specific signaling molecules that promote muscle growth and repair.

For bones, CLCF1 demonstrates dual action—it inhibits osteoclasts that break down bone tissue while promoting osteoblasts that build new bone. This coordinated approach addresses both sides of age-related bone loss.

Importantly, the team discovered that CLCF1 produced by bacteria during exercise creates smaller calcium carbonate crystals than chemically synthesized versions. These microscopic crystals, measuring just 30.7 nanometers compared to 61.1 nanometers for artificial versions, create denser and stronger bone structures.

Blocking Studies Confirm Importance

To confirm CLCF1’s essential role, researchers created a molecular blocker called eCNTFR that prevents the protein from working. When mice received this blocker during exercise training, they lost all the typical benefits of physical activity.

Exercise normally upregulates genes involved in energy metabolism and muscle function, but the blocker completely eliminated these improvements. This definitively proved that CLCF1 mediates exercise’s positive effects on musculoskeletal health.

Transgenic Mice Show Long-term Benefits

Scientists also created transgenic mice that continuously produce elevated CLCF1 levels. These animals demonstrated superior muscle function, enhanced grip strength, improved running capacity, and increased bone mass compared to normal mice.

The transgenic mice exhibited larger muscle fibers and better glucose tolerance, suggesting that maintaining higher CLCF1 levels could provide sustained benefits for aging muscles and bones.

Clinical Implications

The findings offer several potential therapeutic approaches. CLCF1 levels in blood could serve as a biomarker to monitor exercise effectiveness in older adults. More ambitiously, CLCF1 supplements might help elderly individuals who cannot exercise intensively due to physical limitations.

The research also suggests that resistance training may be particularly important for older adults, as this exercise type most effectively stimulates CLCF1 production even in aging muscles.

Current treatments for age-related muscle loss (sarcopenia) and bone weakness (osteoporosis) address these conditions separately. CLCF1’s ability to simultaneously improve both muscle and bone health could represent a significant advancement in treating musculoskeletal aging.

The study involved human participants across multiple cohorts and was supported by several South Korean research foundations, indicating strong institutional backing for this line of research.