What if your muscles could make a molecule that slows aging? New research (Kang et al., 2025) published in Nature Communications suggests they can. This youth-boosting myokine is called CLCF1. Released by skeletal muscle during exercise, CLCF1 helps build muscle strength, preserve bone density, and promote longevity.
However, not all types of exercise trigger CLCF1 equally. Findings in younger vs. older people suggest that resistance training more effectively activates this exercise-induced molecule as we age.
CLCF1: A Molecule With Youthful Potential
CLCF1 (cardiotrophin-like cytokine factor 1) is a myokine, a type of signaling protein released by muscle cells (myocytes) during physical activity.
In young adults, both resistance training and high-intensity interval training (HIIT) resulted in a measurable increase in circulating CLCF1 immediately after working out. Active younger adults who regularly did cardio or lifted weights had significantly higher baseline levels of this myokine compared to their less active age-matched peers.
However, in older adults, aerobic exercise (like walking on a treadmill for an hour) didn’t significantly increase CLCF1 levels—either immediately after exercise or after several weeks of consistent cardio. The good news? A thrice-weekly resistance training program triggered a significant increase in CLCF1 levels after 12 weeks, rejuvenating aging muscles and bones.
This delayed response to increasing CLCF1 underscores the importance of incorporating resistance training into your weekly routine earlier in the aging process. It can also serve as a source of motivation for sticking with a strength-training program in later adulthood.
Why Cardio Alone May Not Be Enough
The latest exercise-induced myokine study also examined older mice and found a similar pattern of CLCF1 secretion. Unlike their younger counterparts, older mice didn’t release much CLCF1 after a single session of high-intensity treadmill running. Over time, their baseline levels remained lower, and their muscles exhibited a stunted myokine response to cardiorespiratory exercise.
Interestingly, the gene that codes for CLCF1 didn’t decline much with age, but the partner protein needed to secrete it—called CRLF1 (cytokine receptor-like factor 1)—did. Low levels of CRLF1 may explain why older muscle cells don’t automatically release as much CLCF1 during aerobic activity.
To investigate how CLCF1 itself may promote resilience in aging muscles, the researchers directly administered recombinant CLCF1 to older mice. Even though the mice couldn’t perform muscle-loading workouts like humans do, the injected myokine still led to gains in strength and bone density—suggesting that CLCF1 plays a direct role in supporting musculoskeletal health. On the flip side, blocking CLCF1 action blunted this myokine’s ability to revive aging muscles and bones.
In a June 2025 news release, senior author Yong Ryoul Yang of the Aging Convergence Research Group explained,
“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. In particular, the findings offer new directions for treating age-related sarcopenia and osteoporosis.”
Strength Training Works Like Compound Interest
Much like cardio, strength training is an investment in long-term health and well-being. Each session might seem like a small deposit. However, over time, these daily investments accumulate and deliver exponential benefits—especially when your muscles release proteins like CLCF1, which help prevent frailty and promote resilience.
Scientists are still exploring how CLCF1 might be harnessed for future therapies aimed at preventing age-related muscle loss and porous bones. That said, numerous science-backed studies demonstrate that resistance training is crucial for offsetting declines in lean muscle mass and bone density, that often occur after midlife.
Take-Home Message: Resistance Training Is Key to Healthy Aging
The latest research (2025) suggests that weightlifting or other forms of resistance training are the most effective way to reawaken youth-supporting molecular activity in aging muscles.
Even if you’re starting later in life, it’s never too late. Research shows that consistent resistance training can boost strength, protect bone density, and help maintain mobility well into older adulthood.
Simple strength exercises—such as bodyweight squats, resistance bands, or light dumbbells—can be enough to activate CLCF1’s benefits if performed consistently. In the long run, the effort you put in now may help you stay stronger, steadier, and more resilient for years to come.