Human primary myoblasts derived from paraspinal muscle reflect donor age as an experimental model of sarcopenia

Abstract

Background: Low back pain is a general phenomenon of aging, and surgery is an unavoidable choice to relieve severe back pain. The discarded surgical site during surgery is of high value for muscle and muscle-related research. This study investigated the age-dependent properties of patients' paraspinal muscles at the cellular level.

Methods: To define an association of paraspinal muscle degeneration with sarcopenia, we analyzed lumbar paraspinal muscle and myoblasts isolated from donors of various ages (25-77 years). Preoperative evaluations were performed by bioimpedance analysis using the InBody 720, magnetic resonance (MR) imaging of the lumbar spine, and lumbar extension strength using a lumbar extension dynamometer. In addition, the growth and differentiation capacity of myoblasts obtained from the donor was determined using proliferation assay and western blotting.

Results: The cross-sectional area of the lumbar paraspinal muscle decreased with age and was also correlated with the appendicular skeletal muscle index (ASM/height²). Human primary myoblasts isolated from paraspinal muscle preserved their proliferative capacity in vitro, which tended to decrease with donor age. The age-dependent decline in myoblast proliferation was correlated with levels of cell cycle inhibitory proteins (p16INK4a, p21CIP1, and p27KIP1) associated with cellular senescence. Primary myoblasts isolated from younger donors differentiated into multinucleate myotubes earlier and at a higher rate than those from older donors in vitro. Age-dependent decline in myogenic potential of the isolated primary myoblasts was likely correlated with the inactivation of myogenic transcription factors such as MyoD, myogenin, and MEF2c.

Conclusions: Myoblasts isolated from human paraspinal muscle preserve myogenic potential that correlates with donor age, providing an in vitro model of sarcopenia.

Keywords: Donor age; Human primary myoblast; Lumbar paraspinal muscle; Myogenesis; Sarcopenia.