Cannabinoid receptor 1 expression is higher in muscle of old vs. young males, and increases upon resistance exercise in older adults

Sebastiaan Dalle,Katrien Koppo

doi:10.1038/s41598-021-97859-3

Abstract

Aged skeletal muscle undergoes metabolic and structural alterations eventually resulting in a loss of muscle strength and mass, i.e. age-related sarcopenia. Therefore, novel targets for muscle growth purposes in elderly are needed. Here, we explored the role of the cannabinoid system in muscle plasticity through the expression of muscle cannabinoid receptors (CBs) in young and old humans. The CB1 expression was higher (+ 25%; p = 0.04) in muscle of old (≥ 65 years) vs. young adults (20–27 years), whereas CB2 was not differently expressed. Furthermore, resistance exercise tended to increase the CB1 (+ 11%; p = 0.055) and CB2 (+ 37%; p = 0.066) expression in muscle of older adults. Interestingly, increases in the expression of CB2 following resistance exercise positively correlated with changes in key mechanisms of muscle homeostasis, such as catabolism (FOXO3a) and regenerative capacity (Pax7, MyoD). This study for the first time shows that CB1 is differentially expressed with aging and that changes in CB2 expression upon resistance exercise training correlate with changes in mediators that play a central role in muscle plasticity. These data confirm earlier work in cells and mice showing that the cannabinoid system might orchestrate muscle growth, which is an incentive to further explore CB-based strategies that might counteract sarcopenia.

Highlights

Ageing is associated with changes that eventually affect health
Skeletal muscle CB1 expression was higher in healthy, old adults (65–84 years) compared to young adults (20–27 years; + 25%; Cohen’s d = 0.73; p = 0.045), whereas CB2 was not differently expressed between age groups
It was shown in mice that cannabinoid receptors (CBs) are key players in the regulation of myogenicity and muscle metabolism, both features that are affected with advancing age, and that contribute to sarcopenia

Summary

Introduction

Ageing is associated with changes that eventually affect health (span). Skeletal muscle is key for mobility, and fulfills central metabolic functions, such as substrate storage and oxidation. There is a gradual decline in muscle strength and muscle mass, referred to as sarcopenia[1]. This condition decreases the quality of life and health through an increased risk for immobility, social isolation and metabolic conditions such as type 2 diabetes. The cannabinoid system is composed of endocannabinoids, e.g. anandamide and 2-arachidonoylglycerol (2-AG), which are lipid mediators binding to the cannabinoid receptor type 1 ( CB1) and C B2 These CBs are expressed in many tissues, and most ubiquitously in the nervous and immune system, which might explain the central role of the cannabinoid system in neural processes and in the inflammatory signaling. Recent developments in mice indicate that CB signaling interferes with muscle m etabolism[19], muscle m aintenance[15] and regenerative processes[13]

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Conclusion