Exercise-Induced Biomarker Modulation in Sarcopenia: From Inflamm-Aging to Muscle Regeneration

Abstract

Sarcopenia is a progressive, age-related loss of skeletal muscle mass, strength, and function, strongly associated with frailty, disability, and chronic disease. Its pathogenesis involves chronic low-grade inflammation, hormonal imbalance, and impaired anabolic signaling, making biomarkers essential for diagnosis, prognosis, and intervention monitoring. This review systematically analyzes randomized controlled trials (RCTs) evaluating the impact of physical exercise on biomarkers relevant to sarcopenia. Exercise modulates both pro-inflammatory markers (e.g., IL-6, TNF-α, CRP) and anti-inflammatory cytokines (e.g., IL-10, IL-15), while also affecting growth factors like IGF-1, myostatin, and follistatin. These changes support muscle anabolism, reduce catabolic signaling, and improve physical performance. In addition, we highlight a growing class of emerging exerkines, including irisin, apelin, beta-aminoisobutyric acid (BAIBA), decorin, brain-derived neurotrophic factor (BDNF), and meteorin-like factor (Metrnl). These molecules exhibit promising roles in mitochondrial health, lipid metabolism, muscle regeneration, and immune modulation, key processes in combating inflamm-aging and sarcopenic decline. Despite encouraging findings, biomarker responses remain heterogeneous across studies, limiting translational application. The integration of biomarker profiling with exercise prescription holds the potential to personalize interventions and guide precision medicine approaches in sarcopenia management. Future large-scale, standardized trials are needed to validate these biomarkers and optimize exercise protocols for aging populations.

Keywords: exerkines; inflamm-aging; muscle wasting.

Figure 1

Impact of Physical (In)Activity on Biomarkers and Muscle Health in Older Adults. Schematic representation of the effects of physical activity on selected anabolic and inflammatory biomarkers in older adults. Physical inactivity is associated with an increase in pro-inflammatory and catabolic factors (e.g., IL-6, TNF-α, CRP, myostatin), promoting sarcopenic decline. In contrast, regular exercise stimulates the expression of anabolic and anti-inflammatory mediators (e.g., IGF-1, IL-10, IL-15, follistatin, irisin), contributing to muscle preservation and functional recovery. The upward (↑) and downward (↓) arrows indicate the direction of change in circulating biomarker levels. Specifically, ↑ represents an increase, and ↓ represents a decrease, as influenced by physical activity or inactivity in the context of muscle aging.

Figure 2

Emerging Exerkines: Key Molecular Mediators of Exercise with Therapeutic Potential in Sarcopenia. Overview of the emerging exercise-responsive biomarkers discussed in Section 8. These molecules, including myokines, cytokines, neurotrophins, and epigenetic regulators, are modulated by physical activity and play key roles in muscle regeneration, metabolic homeostasis, and the pathophysiology of sarcopenia. Each segment corresponds to one of the following biomarkers: Apelin (8.1), Brain-Derived Neutrophic Factor (BAIBA—(8.2), Brain-derived neurotrophic factor (BDNF—8.3), Decorin (8.4), Fibroblast growth factor 21 (FGF21—8.5), Growth differentiation factor 15 (GDF15—8.6), Interleukin 7 (IL-7—8.7), Meteorin-like protein (Metrnl—8.8), and microRNAs (8.9). These factors represent potential diagnostic and therapeutic targets for personalized exercise interventions in aging populations.