Biomarkers of muscle quality: N‐terminal propeptide of type III procollagen and C‐terminal agrin fragment responses to resistance exercise training in older adults

Abstract

BackgroundN-terminal peptide of procollagen type III (P3NP) and C-terminal agrin fragment (CAF) are circulating biomarkers that are related to lean body mass in older adults. P3NP is a circulating marker reflective of muscular structural remodeling while CAF is a circulating marker of neuromuscular remodeling. As resistance exercise is an established intervention that can effectively improve muscle quality, we sought to evaluate circulating biomarker changes corresponding to a resistance exercise intervention in older adults.MethodsTwenty-three older adults (aged 61 to 85 years) were randomized into an intervention (6-week resistance training) or control group. Resting circulating P3NP, CAF, lean body mass (LBM), muscle cross-sectional area (CSA), muscle strength, and muscle quality were determined at baseline and after the intervention or control period by enzyme-linked immunosorbent assay, dual-energy X-ray absorptiometry, ultrasound, leg extension, and relative strength, respectively. Changes in circulating biomarkers and measures of muscle mass and quality were evaluated with repeated-measures analysis of variance; clinical interpretations were made with magnitude-based inferences, and relationships between variables were evaluated with bivariate correlations.ResultsThe short-term resistance exercise intervention was effective at improving muscle quality by 28 % (p < 0.001) despite no significant changes in lean body mass. Baseline circulating P3NP was somewhat lower in older women (4.15 ± 1.9 ng/mL) compared with older men (4.81 ± 2.1 ng/mL). The exercise intervention tended to increase circulating P3NP (baseline = 4.53 ± 1.80 to post = 4.88 ± 1.86) and was significantly correlated with changes in LBM (r = 0.422, p = 0.045). At baseline, women (3.91 ± 1.12 pg/mL) had somewhat higher circulating CAF than men (3.47 ± 1.37 pg/mL). Circulating CAF increased by 10.4 % (3.59 to 4.00 pg/ml) in older adults following 6 weeks of resistance exercise training. Changes in circulating CAF were significantly related to changes in CSA of the vastus lateralis (r = 0.542, p = 0.008).ConclusionsAssessment of P3NP and CAF from blood samples may provide minimally invasive and clinically informative measures of skeletal muscle status in older adults. Circulating CAF appears to increase in response to short-term resistance exercise training in older adults to a clinically meaningful magnitude. Changes in circulating P3NP in response to the intervention were less clear but appear to reflect muscle hypertrophy. Further research is needed to elucidate whether P3NP, CAF, or other biomarkers can reflect muscle qualitative adaptations with larger and longer studies.

Muscle Quality in Aging: a Multi-Dimensional Approach to Muscle Functioning with Applications for Treatment

“…We found that circulating CAF increased to a clinically meaningful magnitude while changes in circulating P3NP were less clear, but appeared to reflect muscle hypertrophy [177]. While assessment of P3NP and CAF from blood samples may provide minimally invasive and clinically informative measures of skeletal muscle status in older adults, further research is needed to elucidate whether P3NP, CAF, or other biomarkers can reflect muscle qualitative adaptations with larger and longer studies.…”

“…We evaluated changes in circulating concentration of P3NP and CAF in response to a preliminary intervention designed to increase muscle quality but not mass [177]. We found that circulating CAF increased to a clinically meaningful magnitude while changes in circulating P3NP were less clear, but appeared to reflect muscle hypertrophy [177].…”

Loss of muscle mass: Current developments in cachexia and sarcopenia focused on biomarkers and treatment

“…94,95 Such factors include for instance leptin, 96 ghrelin, 97 and obestatin 98 which are all thought to play a major role in cancer cachexia. These emerging biomarkers were MMP-generated degradation fragment of collagen 6 (C6M) 68 Type VI collagen N-terminal globular domain epitope (IC6) 68 N-terminal propeptide of type III procollagen (P3NP) 69 C-terminal agrin fragment (CAF) 69 Methyl-d 3 -Methylhistidine (D-3MH) 70 Growth differentiating factor-15 (GDF-15) 71 Follistatin (FST) 72 Irisin 72 Ghrelin 73 Leptin 73 β-Dystroglycan 74 Dystrophin 74 Tartrate-resistant acid phosphatase 5a (TRACP5a) [75][76][77][78] MMP, matrix metalloproteinase. investigated in oncologic patients as diagnostic and/or predictive markers, as well as their impact on patient survival.…”

Cardiac cachexia: hic et nunc

“…87 It is released into circulation during collagen synthesis in soft lean tissue, and its levels have been associated with changes in the lean mass of elderly patients. 63,91 Myostatin Although it seems a natural candidate for an atrophy biomarker, as it directly mediates catabolic signaling, the data of a recent study in CC could not confirm the role of circulating myostatin as a biomarker for muscle wasting in humans.…”