CHRNA1 induces sarcopenia through neuromuscular synaptic elimination

Exp Gerontol. 2022 Sep:166:111891. doi: 10.1016/j.exger.2022.111891. Epub 2022 Jul 6.

Abstract

Sarcopenia seriously affects the quality of life of the elderly, but its molecular mechanism is still unclear. Degeneration in muscle innervation is related to age-related movement disorders and muscle atrophy. The expression of CHRNA1 is increased in the skeletal muscle of the elderly, and in aging rodents. Therefore, we investigated whether CHRNA1 induces the occurrence and development of sarcopenia. Compared with the control group, local injection of AAV9-CHRNA1 into the hindlimb muscles decreased the percentage of muscle innervation. At the same time, the skeletal muscle mass decreased, as manifested by a decrease in the gastrocnemius mass index and the cross-sectional area of the muscle fibers. The function of skeletal muscle also decreased, which was manifested by decreases of compound muscle action potential and muscle contractility. Therefore, we concluded that upregulation of CHRNA1 can induce and aggravate sarcopenia.

Keywords: CHRNA1; NMJs; Sarcopenia; Skeletal muscle; calpain1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Mice
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / physiology
  • Muscular Atrophy / pathology
  • Quality of Life
  • Receptors, Nicotinic*
  • Sarcopenia*

Substances

  • CHRNA1 protein, mouse
  • Receptors, Nicotinic