Neuromuscular Degradation and Muscle Decline in Older Men Physically Competent Versus Incompetent To Perform the Short Physical Performance Battery

Purpose: Older adults who fail to complete the short physical performance battery (SPPB), exhibit advanced muscle decline. However, the role of neuromuscular junction (NMJ) disintegration in these physically incompetent people remains insufficiently characterized. Methods: We recruited physically competent (n = 167) and incompetent (n = 160) geriatric men based on their ability to complete the SPPB. We measured handgrip strength (HGS), skeletal muscle mass index (SMI), bone mineral density (BMD), and plasma markers of NMJ degradation (c-terminal agrin-fragment-22; CAF22) and neurodegeneration (neurofilament light-chain; NfL) at baseline and one year later. Results: At baseline, the physically incompetent participants exhibited lower HGS, SMI, and BMD and higher plasma CAF22 and NfL than the physically competent men (all p < 0.05). Elevated CAF22 exhibited dynamic correlations with low HGS and BMD in these participants during the study period (both p < 0.05). Mediation analysis revealed significant mediating effects of SMI (percent mediation; P_M=7.57%), BMD (P_M=27.8%), low vitamin D (P_M=8.27%), NfL (P_M=18.4%), and oxidative stress (P_M=13.1%) on the inverse relationship between CAF22 and HGS (all p < 0.05). Conclusion: Altogether, NMJ disintegration contributes to low HGS in physically incompetent geriatric men. Targeting the NMJ may be a therapeutic option to restore muscle strength and physical capacity in old age.