Physical frailty and sarcopenia are two common and largely overlapping geriatric conditions upstream of the disabling cascade. The lack of a unique operational definition for physical frailty and sarcopenia and the complex underlying pathophysiology make the development of biomarkers for these conditions extremely challenging. Indeed, the current definitional ambiguities of physical frailty and sarcopenia, together with their heterogeneous clinical manifestations, impact the accuracy, specificity, and sensitivity of individual biomarkers proposed so far. In this review, the current state of the art in the development of biomarkers for physical frailty and sarcopenia is presented. A novel approach for biomarker identification and validation is also introduced that moves from the ‘one fits all’ paradigm to a multivariate methodology.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcsm.12051

Biomarkers for physical frailty and sarcopenia: state of the science and future developments

Inflammatory biomarkers of frailty.

Loss of muscle mass and strength with aging, termed sarcopenia is accelerated in several comorbidities including chronic heart failure (CHF) and chronic obstructive pulmonary diseases (COPD). However, the effective circulating biomarkers to accurately diagnose and assess sarcopenia are not known. We recruited male healthy controls and patients with CHF and COPD (n = 81–87/group), aged 55–74 years. Sarcopenia was clinically identified based on hand-grip strength, appendicular skeletal muscle index and physical capacity as recommended by the European working group for sarcopenia. The serum levels of amino-terminal pro-peptide of type-III procollagen, c-terminal agrin fragment-22, osteonectin, irisin, fatty acid-binding protein-3 and macrophage migration inhibitory factor were significantly different between healthy controls and patients with CHF and COPD. Risk scores for individual biomarkers were calculated by logistic regressions and combined into a cumulative risk score. The median cutoff value of 3.86 was used to divide subjects into high- and low-risk groups for sarcopenia with the area under the curve of 0.793 (95% CI = 0.738–0.845, p < 0.001). A significantly higher incidence of clinical sarcopenia was found in high-risk group. Taken together, the battery of biomarkers can be an effective tool in the early diagnosis and assessment of sarcopenia.

/pdf/prediction-of-sarcopenia-using-a-battery-of-circulating-53ou416gw7.pdf

Prediction of sarcopenia using a battery of circulating biomarkers.

Sarcopenia is a gradual loss of skeletal muscle mass and function with aging. Given that sarcopenia has been recognized as a disease entity, effective molecular biomarkers for early diagnosis are required. We recruited 46 normal subjects and 50 patients with moderate sarcopenia aged 60 years and older. Sarcopenia was clinically identified on the basis of the appendicular skeletal muscle index by applying cutoff values derived from the Asian Working Group for Sarcopenia. The serum levels of 21 potential biomarkers were analyzed and statistically examined. Interleukin 6, secreted protein acidic and rich in cysteine, macrophage migration inhibitory factor, and insulin-like growth factor 1 levels differed significantly between the normal and sarcopenia groups. However, in each case, the area under the receiver operating characteristics curve (AUC) was <0.7. Subsequent combination of the measurements of these biomarkers into a single risk score based on logistic regression coefficients enhanced the accuracy of diagnosis, yielding an AUC value of 0.763. The best cutoff value of 1.529 had 70.0% sensitivity and 78.3% specificity (95% CI = 2.80–21.69, p < 0.0001). Combined use of the selected biomarkers provides higher diagnostic accuracy than individual biomarkers, and may be effectively utilized for early diagnosis and prognosis of sarcopenia.

/pdf/prediction-of-sarcopenia-using-a-combination-of-multiple-12ippfo9fa.pdf

Prediction of sarcopenia using a combination of multiple serum biomarkers.

In a pilot randomized clinical trial, participants aged ≥60 years (n = 35) with physical limitations and symptomatic knee osteoarthritis (OA) were randomized to 12 weeks of lower-body low-load resistance training with blood-flow restriction (BFR) or moderate-intensity resistance training (MIRT) to evaluate changes in muscle strength, pain, and physical function. Four exercises were performed three times per week to volitional fatigue using 20% and 60% of one repetition maximum (1RM). Study outcomes included knee extensor strength, gait speed, Short Physical Performance Battery (SPPB) performance, and pain via the Western Ontario and McMaster Universities OA Index (WOMAC). Per established guidance for pilot studies, primary analyses for the trial focused on safety, feasibility, and effect sizes/95% confidence intervals of dependent outcomes to inform a fully-powered trial. Across three speeds of movement, the pre- to post-training change in maximal isokinetic peak torque was 9.96 (5.76, 14.16) Nm while the mean difference between groups (BFR relative to MIRT) was -1.87 (-10.96, 7.23) Nm. Most other directionally favored MIRT, though more spontaneous reports of knee pain were observed (n = 14) compared to BFR (n = 3). BFR may have lower efficacy than MIRT in this context-though a fully-powered trial is needed to definitively address this hypothesis.

Blood-Flow Restriction Resistance Exercise for Older Adults with Knee Osteoarthritis: A Pilot Randomized Clinical Trial.

Background
Procollagen type III N-terminal peptide (P3NP) is released during collagen synthesis in muscle. Increased circulating P3NP is a marker not only of muscle growth, but also of muscle repair and fibrosis. Thus, P3NP may be a potential biomarker for sarcopenia.

Procollagen type III N-terminal peptide (P3NP) and lean mass: a cross-sectional study

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Procollagen type III N-terminal peptide (P3NP) and lean mass: a cross-sectional study