How To Increase Your Levels Of A Natural Protein That Suppresses Bone Loss

The cycle of bone resorption and deposition must remain balanced to keep your bones strong and healthy. Studies have identified an immune factor that moderates bone resorption, preventing runaway resorption from weakening your bones.

Although this factor diminishes with age, a new study has found that exercise can prevent its decline and protect bones. We'll examine the details, and you'll learn how to use this discovery to prevent bone loss and preserve your physical health and independence.

All About Cardiotrophin-Like Cytokine Factor 1

Cardiotrophin-like cytokine factor 1, or CLCF1, is a molecule produced by immune cells. Studies have observed that CLCF1 is reduced in participants with postmenopausal osteoporosis.

A 2021 study in the journal Bone investigated the functional role of CLCF1 in the genesis of osteoclasts (bone resorbing cells) and bone loss associated with osteoporosis. The researchers administered recombinant CLCF1 to ovariectomized mice and found that it repressed excessive bone loss.¹

They also observed bone tissue treated with CLCF1 and found a significant reduction in the number of differentiated osteoclasts. At the same CLCF1 dosage, no negative effects were observed on the differentiation of osteoblasts (bone building cells).

They concluded that CLCF1 plays a critical role in the regulation of bone remodeling, helping to prevent excess bone resorption. The study was conducted using mice, so while this evidence is compelling, the results need to be confirmed with human participants.¹

These findings suggest that CLCF1 could serve as the basis for a new osteoporosis drug. However, CLCF1 is a protein that the body produces naturally. A more recent study has unlocked the key to increasing your natural production of this osteoclast-regulating factor.

Synopsis

A study with mice found that the immune cell-derived molecule CLCF1 suppresses the production of bone-resorbing osteoclasts, but not bone-creating osteoblasts. Ovariectomized mice administered CLCF1 experienced less bone loss. Human studies have yet to confirm this effect in humans.

Study Finds Exercise-Induced CLCF1 Protects Bone

A 2025 study published in the journal Nature Communications examined how exercise affects CLCF1 levels and the resulting impact on bone health. The researchers noted that levels of CLCF1 decreased with age, but that exercise significantly upregulated CLCF1 levels in both humans and rodents.²

The researchers analyzed muscle biopsies taken in a study investigating the effect of acute resistance exercise, progressive resistance training, and aging on gene expression in human skeletal muscle.

The study included two groups: young adults (ages 24–25) and older adults (ages 78–84). They participated in a 12-week progressive resistance training program, with muscle biopsies collected before and after a single session, as well as before the first and last sessions of the 12-week program. The researchers found that the resistance training increased CLCF1 levels.²

Similar results were observed in other studies involving older adults who completed either 16 weeks of resistance training or 12 weeks of resistance band exercises.. Both studies showed significantly elevated CLCF1 levels in older adults following the training programs.²

They concluded that CLCF1 is an exercise-induced protein that attenuates age-related decline in muscle and bone. Their findings indicate that while CLCF1 expression declines with age, it can be restored through resistance exercise.

Synopsis

A 2025 study examined data from research with human participants that measured the impact of resistance training programs on the CLCF1 levels of older adults. They found that CLCF1 is an exercise-induced protein that attenuates age-related decline in muscle and bone.

One Signal With Two Recipients

CLCF1 is particularly important because it targets both muscle and bone simultaneously. These two tissues typically weaken together as we age, leading to frailty, falls, and fractures.

However, CLCF1 provides a path to strengthening both tissues. In a study with 20-month-old mice (roughly the equivalent of 80 human years), two weeks of CLCF1 injections significantly improved the mice's grip strength and running endurance. The researchers found that their muscle fibers grew larger, and their bones became denser and stronger.

While mouse studies must be interpreted with caution, these outcomes align with current knowledge of CLCF1 function in humans.

This research brings us back to a common refrain: exercise builds both muscle and bone to prevent falls and fractures. CLCF1 is remarkable in that it serves as a signaling factor that instructs the body about the need for more muscle mass and more bone mass.

The studies revealed that CLCF1 is required for exercise to generate these benefits — when the protein was blocked in mice, exercise no longer produced positive effects.

Notably, different types of exercise elicited different responses. Resistance training increased CLCF1 levels, but moderate-intensity aerobic exercise, such as walking, did not. This suggests that CLCF1 release might require a certain threshold of exercise intensity.

This finding reinforces the importance of including higher-intensity exercises like resistance training in your routine to stimulate CLCF1 production and support muscle and bone health..

Synopsis

CLCF1 signals the need for both bone and muscle formation. Elderly mice injected with the protein saw improvements in muscle strength and bone strength. However, it seems that high-intensity exercise, such as resistance training, is required to trigger an increase in CLCF1 levels.

What This Means To You

Exercise triggers a signalling cascade in your body that activates cells responsible for building muscle and bone. The pharmaceutical industry will continue to create drugs that imitate these signals, but you don't need those drugs or their side effects, because exercise sends these signals naturally.

Create varied and enjoyable workout routines that support your bone health. Try SaveTrainer to help you do it. SaveTrainer is the Save Institute's online video workout platform designed for bone health. You'll find a large variety of workouts led by professional trainers with options for every ability level. Because SaveTrainer is online, you can access it anywhere, anytime to get the exact workout you need.

Let physical activity signal to your body that you want it to remain strong, functional, and resilient for years to come.

References

¹ https://pubmed.ncbi.nlm.nih.gov/34364014/

² https://www.nature.com/articles/s41467-025-59959-w