Exercise Rewires Sarcopenia Biomarkers From Inflammation to Muscle Renewal

Sarcopenia, officially classified as a treatable disease with an ICD-10-CM code since 2016, represents one of the most clinically significant challenges of an aging global population. Affecting 10–27% of adults over 60 and up to 50% of those beyond 80, it is driven by a convergence of chronic low-grade inflammation ('inflammaging'), hormonal decline, impaired anabolic signaling, and sedentary behavior ('inflamm-inactivity'). No pharmacological treatments are currently approved, making exercise the most evidence-supported intervention available. This review synthesized six RCTs published between 2019 and 2025 to characterize how different exercise modalities reshape the biomarker landscape of sarcopenia.

The six included RCTs involved participants with a mean age of 69 years (range 38–84) and intervention durations averaging 17 weeks (range 8–24 weeks). Five of six studies used resistance training alone; one employed a multicomponent protocol combining resistance, aerobic, and balance exercise. Methodological quality was high, with four studies rated 'Excellent' (9/10) and two rated 'Good' (7/10) on an adapted PRISMA/CONSORT checklist. Average dropout was 17% (range 0–43%). TNF-α and IL-6 were the most commonly assessed biomarkers, each measured in 57% of studies, followed by myostatin (43%), CRP and IGF-1 (29%), and IL-10, IL-15, follistatin, insulin, BDNF, and irisin (14% each).

Exercise consistently suppressed pro-inflammatory markers. All four RCTs assessing IL-6 reported reductions following resistance or combined training. TNF-α decreased significantly in the Ghayomzadeh et al. trial after six months of combined training, with greater effects when exercise was paired with whey protein supplementation (Griffen et al.). CRP reductions were more variable across the two studies that measured it, with differences attributed to assay sensitivity, baseline inflammation, and intervention length. On the anabolic side, IGF-1 rose significantly in Ghayomzadeh et al.'s combined protocol, while Griffen et al. found that resistance plus protein supplementation produced more robust endocrine responses than resistance alone. Myostatin—a potent inhibitor of muscle growth via Smad2/3 signaling—declined following training, with concurrent rises in its inhibitor follistatin, shifting the ratio favorably toward anabolism.

Anti-inflammatory cytokines IL-10 and IL-15 emerged as important exercise-responsive mediators. IL-15, co-secreted with myostatin antagonist activity, promotes satellite cell proliferation and muscle hypertrophy, while IL-10 dampens NF-κB-driven catabolism. The review also highlights a growing class of exerkines—molecules released systemically during exercise regardless of tissue of origin. Irisin, cleaved from FNDC5, activates PGC-1α signaling, promotes mitochondrial biogenesis, and reduces adipogenesis. Apelin improves mitochondrial function and satellite cell activation. BAIBA (beta-aminoisobutyric acid) drives browning of white adipose tissue and reduces fat infiltration of muscle. Decorin inhibits myostatin and supports extracellular matrix remodeling. BDNF supports neuromuscular junction integrity, and meteorin-like factor (Metrnl) modulates immune function and energy metabolism. These molecules were not uniformly assessed across the included RCTs but represent a frontier for future biomarker research.

The review highlights critical limitations and translational gaps. Biomarker responses were heterogeneous across studies due to differences in exercise protocols, participant characteristics, assay methods, and follow-up durations. No included RCT evaluated aerobic exercise in isolation. Sample sizes were generally modest, and few studies stratified results by sex, age subgroup, or sarcopenia severity. The authors conclude that integrating comprehensive biomarker profiling with personalized exercise prescription holds strong potential for precision medicine approaches to sarcopenia, but large-scale, standardized trials with validated biomarker panels are urgently needed.