bims-creces Biomed News
on Creatine and cell stress
Issue of 2025–12–28
two papers selected by
James Heilman, Oregon Health & Science University
  1. Guanidinoacetic Acid Supplementation: A Mechanistic Model of Utilization and Clearance.
  2. Exercise-Induced Biomarker Modulation in Sarcopenia: From Inflamm-Aging to Muscle Regeneration.
  1. J Diet Suppl. 2025 Dec 24. 1-11
    Guanidinoacetic Acid Supplementation: A Mechanistic Model of Utilization and Clearance.
    Sergej M Ostojic.
      Guanidinoacetic acid, the immediate precursor of creatine, is gaining renewed attention as a nutritional and therapeutic agent capable of enhancing tissue bioenergetics. Yet, a comprehensive mechanistic framework describing how exogenous guanidinoacetic acid is processed in the human body is lacking. This concept paper proposes an integrated metabolic model of guanidinoacetic acid utilization, synthesizing available kinetic evidence on its enzymatic conversion via guanidinoacetate N-methyltransferase (GAMT), cellular trafficking through the creatine transporter (SLC6A8), and ancillary routes including reverse amidinotransferase activity, oxidative degradation, and renal handling. Our modeling reveals that GAMT achieves near-saturation at relatively low guanidinoacetic acid intakes, whereas SLC6A8 transport capacity remains underutilized even at higher systemic guanidinoacetic acid levels due to competitive interactions with creatine. Secondary pathways contribute proportionally less to overall guanidinoacetic acid fate but may assume greater importance in metabolic stress, aging, or creatine-deficiency states. By estimating theoretical distributions of guanidinoacetic acid flux across these pathways for commonly used oral doses (1-4 g/day), this manuscript provides a mechanistic foundation for optimizing guanidinoacetic acid supplementation strategies. The model highlights clinically relevant opportunities-such as enhancing creatine repletion, supporting mitochondrial function, and addressing creatine-deficiency syndromes-while identifying key parameters that require in vivo validation. Collectively, this work aims to guide both basic researchers and clinicians toward a more informed and strategic use of guanidinoacetic acid in human nutrition and health.
    Keywords:  GAMT; Guanidinoacetic acid; SLC6A8; bioenergetics; creatine; metabolic modeling
    DOI:  https://doi.org/10.1080/19390211.2025.2606749
  2. Sports (Basel). 2025 Dec 09. pii: 444. [Epub ahead of print]13(12):
    Exercise-Induced Biomarker Modulation in Sarcopenia: From Inflamm-Aging to Muscle Regeneration.
    Federica Marmondi, Vittoria Ferrando, Luca Filipas, Roberto Codella, Piero Ruggeri, Antonio La Torre, Emanuela Luisa Faelli, Matteo Bonato.
      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
    DOI:  https://doi.org/10.3390/sports13120444
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