Low BDNF Linked to Sarcopenia and Worse Gait in Older Adults

Sarcopenia — the age-related loss of muscle mass, strength, and physical performance — affects a growing proportion of older adults globally and dramatically raises fall, disability, and mortality risk. While much research has focused on metabolic and inflammatory drivers, the neurobiological dimension of muscle aging, particularly the brain–muscle axis mediated by BDNF, remains underexplored in community-dwelling populations. This study by Zhang et al. positions BDNF as a clinically meaningful biomarker sitting at the intersection of central neural regulation, systemic inflammation, and lower-limb motor function.

The investigators enrolled 646 adults aged 60 years and older (mean age 70.46 years; 57% women) from five communities in Beijing's Dongcheng District between February and August 2023. Sarcopenia was diagnosed using the 2019 AWGS criteria, requiring low appendicular skeletal muscle mass index (SMI <7.0 kg/m² in men, <5.7 kg/m² in women) combined with low handgrip strength or low physical performance. Gait was captured using the IDEEA multisensor wearable system across a 12-metre walk, yielding 14 parameters spanning periodic (swing time, step time, stride time, support times), kinetic (thigh acceleration, thigh swing work, ground reaction force, foot landing control force, toe-off angle), and spatiotemporal domains (stride frequency, step length, stride length). Plasma BDNF was measured by a validated multiplex immunoassay with CVs under 5%. Inflammatory markers (IL-6, IL-1β, TNF-α, CRP) and antioxidant enzymes (SOD, glutathione reductase, GPx, catalase) were simultaneously quantified.

Of the 646 participants, 65 (10.06%) met AWGS 2019 sarcopenia criteria. Sarcopenic individuals had markedly lower median BDNF levels — 1.82 μg/L versus 4.12 μg/L in non-sarcopenic peers (p=0.003). Spearman correlations confirmed that BDNF tracked positively with SMI (r=0.11, p=0.018), handgrip strength (r=0.27, p<0.001), and gait speed (r=0.32, p<0.001), and negatively with five-times sit-to-stand time (r=−0.34, p<0.001). In fully adjusted multivariable logistic regression controlling for demographics, lifestyle, comorbidities, ADL status, cognition, and depression, each log-unit increase in BDNF was associated with a 29% lower odds of sarcopenia (OR=0.71, 95% CI: 0.63–0.81, p=0.012).

For gait, ln-BDNF was independently and negatively associated with swing time (β=−7.833, p=0.011), step time (β=−12.769, p=0.016), and stride time (β=−0.026, p=0.012) — meaning higher BDNF corresponded to faster, more efficient gait cycles. Positively, higher BDNF predicted greater thigh acceleration (β=0.066, p=0.001), thigh swing work (β=0.039, p<0.001), ground reaction force (β=0.083, p<0.001), foot landing control force (β=0.224, p<0.001), toe-off angle (β=2.061, p<0.001), step frequency (β=1.615, p<0.001), and stride length (β=0.013, p<0.001). These associations held after adjustment for all covariates, underscoring BDNF's independent contribution to neuromuscular performance.

Mediation analyses revealed that IL-1β mediated 14.65% of the BDNF–sarcopenia association, consistent with the mechanistic hypothesis that BDNF suppresses neuroinflammation via TrkB/NF-κB signalling, thereby protecting NMJ integrity and limiting proteolytic muscle loss. IL-6, SOD, and glutathione reductase were also concurrently correlated with BDNF, sarcopenia status, and gait parameters, suggesting a broader neuro-inflammatory-oxidative stress network. The cross-sectional design precludes causal inference, and bioelectrical impedance — though practical — is less precise than DXA for muscle mass estimation. Nonetheless, these findings position plasma BDNF as a tractable, multi-dimensional biomarker of neuromuscular aging that may complement existing sarcopenia diagnostic panels.