Handgrip strength asymmetry as a new biomarker for sarcopenia and individual sarcopenia signatures.

BACKGROUND: Although handgrip strength (HGS) asymmetry has clinical screening utility, its relevance to sarcopenia is unknown. This study examined the relationship between HGS asymmetry and sarcopenia signatures, and explored the relevance of circulating neural/neuromuscular markers. METHODS: 9403 individuals aged 18-92 years participated in this study. Maximal HGS and skeletal muscle index (SMI) were determined using hand dynamometry and DXA. Sarcopenia was diagnosed upon the presence of low HGS and low SMI, according to cohort-specific thresholds. Plasma biomarkers were measured by ELISA in a sub-group of 269 participants aged 50-83 years. Asymmetry was determined as the highest recorded HGS divided by the highest recorded HGS of the opposite hand. Individuals with a ratio > 1.10 were classified as having asymmetrical HGS. RESULTS: Subjects with asymmetrical HGS had significantly lower SMI (7.67 kg/m2 vs 7.71 kg/m2, p = 0.004) and lower HGS (37.82 kg vs 38.91 kg, p < 0.001) than those with symmetrical HGS. In those aged ≥ 50 years asymmetrical HGS was associated with 2.67 higher odds for sarcopenia [95% confidence interval: (CI) = 1.557-4.561, p < 0.001], 1.83 higher odds for low HGS only (CI 1.427-2.342, p < 0.001), and 1.79 higher odds for low SMI only (CI 1.257-2.554, p = 0.001). HGS asymmetry demonstrated acceptable diagnostic accuracy for sarcopenia (AUC = 0.727, CI 0.658-0.796, p < 0.001). Plasma neural cell adhesion molecule concentrations were 19.6% higher in individuals with asymmetrical HGS (185.40 ng/mL vs 155.00 ng/mL, p < 0.001) than those with symmetrical HGS. DISCUSSION: Our findings demonstrate the utility of HGS asymmetry as a screening tool that may complement existing strategies seeking to combat sarcopenia. Biomarker analyses suggest that heightened denervation may be an important aetiological factor underpinning HGS asymmetry.

Plasma neurofilament light levels associate with muscle mass and strength in middle-aged and older adults: findings from GenoFit.

BACKGROUND: Efforts to enhance diagnostic measures for sarcopenia have led to an increased focus on the screening utility of blood-based biomarkers. In this regard, circulating neurofilament light chain (NfL) levels are a potent indicator of axonal damage and have been linked with several neurological disorders. However, despite the strong neurogenic contribution to skeletal muscle health, no studies have explored the relevance of NfL concentrations to sarcopenia. With that in mind, this study aimed to examine the association between plasma NfL concentration and sarcopenic domains. METHODS: Three hundred adults aged between 50 and 83 years participated to this study (male participants, n = 150; mean age: 64.2 ± 8.7 years and female participants, n = 150; mean age: 63.9 ± 8.3 years). Body composition was assessed using dual-energy X-ray absorptiometry, and a skeletal muscle index (SMI) was calculated. Muscle strength was assessed with hand dynamometry. Sarcopenia was classified using the European Working Group on Sarcopenia in Older People criteria. Plasma NfL concentration was determined using a highly sensitive, enzyme-linked immunosorbent assay. RESULTS: Neurofilament light chain levels were associated with grip strength and SMI (P = 0.005 and P = 0.045, respectively) and were significantly elevated in sarcopenic individuals, compared with non-sarcopenic participants (P < 0.001). Individuals with pre-sarcopenia (either low grip strength or low SMI) had significantly higher NfL levels, compared with healthy controls (P = 0.001 and P = 0.006, respectively). Male participants with either low grip strength or low SMI had significantly raised NfL levels (P = 0.006 and P = 0.002, respectively), while in female participants, NfL concentrations were significantly elevated only in those with low grip strength (P = 0.049). NfL concentration displayed acceptable diagnostic accuracy for sarcopenia (area under the curve = 0.726, P < 0.001). CONCLUSIONS: Our study clearly demonstrates the indicative pertinence of circulating NfL levels to sarcopenic domains, supporting its potential use as a biomarker of sarcopenia. More studies are needed, however, to further illuminate the diagnostic value of circulating NfL. Future research should explore whether NfL levels are more powerfully linked with muscle strength than mass and whether sex mediates the relevance of NfL concentrations to sarcopenic phenotypes.

Plasma C-Terminal Agrin Fragment as an Early Biomarker for Sarcopenia: Results From the GenoFit Study.

Barriers associated with direct muscle quantification have prevented a consistent implementation of therapeutic measures for sarcopenia. Recently, the relevance of circulating C-terminal agrin fragment (CAF) as an accessible screening method alternative for sarcopenia has gained credence. Accordingly, this study aimed to verify the pertinence of plasma CAF as a biomarker for sarcopenia. Three hundred healthy adults aged between 50 and 83 years took part in this study. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People criteria. Body composition was assessed using dual-energy x-ray absorptiometry, while muscle strength was examined using hand dynamometry. Plasma CAF concentrations were determined using a commercially available ELISA kit. CAF concentrations were significantly associated with appendicular lean mass (ALM), but not grip strength (p = .028, p = .575, respectively). Plasma CAF concentrations were significantly elevated in sarcopenic individuals compared to nonsarcopenic (p < .001). Overall, individuals with low grip strength or low ALM displayed significantly higher CAF levels compared to healthy controls, after adjusting for age and body mass index (p = .027, p = .003, respectively). In males, those with low grip strength or low ALM had significantly elevated CAF levels (p = .039, p = .027, respectively), while in females, only those with low ALM had significantly raised CAF concentrations, compared to healthy controls (p = .035). Our findings illuminate the potential relevance of CAF as an accessible biomarker for skeletal muscle health. CAF determination may enhance clinical practice by facilitating more widespread treatment strategies for sarcopenia. Nevertheless, future research is needed to confirm the diagnostic pertinence of CAF concentrations in screening for sarcopenia.