Serum C-terminal agrin fragment as a biomarker of age-related neuromuscular decline in men: influence of physical activity
- 1Universite du Quebec a Montreal
Abstract
Aging is accompanied by progressive neuromuscular junction (NMJ) degeneration. The C-terminal agrin fragment (CAF), a circulating product of agrin cleavage, has been proposed as a minimally invasive biomarker of NMJ degradation, but its relationships with neuromuscular and functional characteristics, and the influence of physical activity, remain underexplored. We studied 136 community-dwelling men aged 20-92 years (active, n=87; inactive, n=49). Serum CAF was measured by ELISA. The proportion of NCAM-positive fibers, a marker of myofiber denervation, was assessed in vastus lateralis biopsies (n=127). Neuromuscular outcomes included maximal voluntary isometric contraction (MVIC), lower-limb power, electromechanical delay (EMD), nerve conduction velocities, H/M ratio, central activation ratio, co-activation, and twitch characteristics. Functional capacity was assessed using the 6-minute walk test, alternating step test, Timed Up and Go, sit-to-stand tests, and fast gait speed. Serum CAF increased with age and was positively associated with NCAM-positive fiber proportion. Higher CAF was associated with lower MVIC, lower-limb power and poorer performance on all functional tests. CAF was associated with longer EMD in the overall cohort and in inactive men only, and with a lower H/M ratio in inactive men. No associations were found with nerve conduction velocities, central activation ratio, co-activation, or twitch amplitude. Active men had lower CAF levels than inactive men, particularly after age 70. Serum CAF is associated with age-related declines in neuromuscular and functional capacity and with NCAM-positive fiber prevalence, supporting its utility as an accessible biomarker of NMJ remodeling. Physical activity was associated with a more favorable CAF profile in older men.
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BibTeX
@misc{hammad2026serum,
title = {{Serum C-terminal agrin fragment as a biomarker of age-related neuromuscular decline in men: influence of physical activity}},
author = {R. Hammad and V. Marcangeli and M. Cefis and R. Chaney and K. Desjardins and J. Granet and P. Gaudreau and R. Robitaille and J. A. Morais and M. Aubertin-Leheudre and M. Belanger and G. Gouspillou},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.747348},
url = {https://www.biorxiv.org/content/10.64898/2026.09.02.747348v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Serum C-terminal agrin fragment as a biomarker of age-related neuromuscular decline in men: influence of physical activity
AU - R. Hammad
AU - V. Marcangeli
AU - M. Cefis
AU - R. Chaney
AU - K. Desjardins
AU - J. Granet
AU - P. Gaudreau
AU - R. Robitaille
AU - J. A. Morais
AU - M. Aubertin-Leheudre
AU - M. Belanger
AU - G. Gouspillou
PY - 2026
DA - 2026/09/02
PB - bioRxiv
DO - 10.64898/2026.09.02.747348
UR - https://www.biorxiv.org/content/10.64898/2026.09.02.747348v1
AB - Aging is accompanied by progressive neuromuscular junction (NMJ) degeneration. The C-terminal agrin fragment (CAF), a circulating product of agrin cleavage, has been proposed as a minimally invasive biomarker of NMJ degradation, but its relationships with neuromuscular and functional characteristics, and the influence of physical activity, remain underexplored. We studied 136 community-dwelling men aged 20-92 years (active, n=87; inactive, n=49). Serum CAF was measured by ELISA. The proportion of NCAM-positive fibers, a marker of myofiber denervation, was assessed in vastus lateralis biopsies (n=127). Neuromuscular outcomes included maximal voluntary isometric contraction (MVIC), lower-limb power, electromechanical delay (EMD), nerve conduction velocities, H/M ratio, central activation ratio, co-activation, and twitch characteristics. Functional capacity was assessed using the 6-minute walk test, alternating step test, Timed Up and Go, sit-to-stand tests, and fast gait speed. Serum CAF increased with age and was positively associated with NCAM-positive fiber proportion. Higher CAF was associated with lower MVIC, lower-limb power and poorer performance on all functional tests. CAF was associated with longer EMD in the overall cohort and in inactive men only, and with a lower H/M ratio in inactive men. No associations were found with nerve conduction velocities, central activation ratio, co-activation, or twitch amplitude. Active men had lower CAF levels than inactive men, particularly after age 70. Serum CAF is associated with age-related declines in neuromuscular and functional capacity and with NCAM-positive fiber prevalence, supporting its utility as an accessible biomarker of NMJ remodeling. Physical activity was associated with a more favorable CAF profile in older men.
ER -