Zebrafish models of sarcopenia

Abstract

Sarcopeniathe accelerated age-related loss of muscle mass and functionis an under-diagnosed condition, and is central to deteriorating mobility, disability and frailty in older age. There is a lack of treatment options for older adults at risk of sarcopenia. Although sarcopenia's pathogenesis is multifactorial, its major phenotypesmuscle mass and muscle strengthare highly heritable. Several genome-wide association studies of musclerelated traits were published recently, providing dozens of candidate genes, many with unknown function. Therefore, animal models are required not only to identify causal mechanisms, but also to clarify the underlying biology and translate this knowledge into new interventions. Over the past several decades, small teleost fishes had emerged as powerful systems for modeling the genetics of human diseases. Owing to their amenability to rapid genetic intervention and the large number of conserved genetic and physiological features, small teleostssuch as zebrafish, medaka and killifishhave become indispensable for skeletal muscle genomic studies. The goal of this Review is to summarize evidence supporting the utility of small fish models for accelerating our understanding of human skeletal muscle in health and disease. We do this by providing a basic foundation of the (zebra)fish skeletal muscle morphology and physiology, and evidence of muscle-related gene homology. We also outline challenges in interpreting zebrafish mutant phenotypes and in translating them to human disease. Finally, we conclude with recommendations on future directions to leverage the large body of tools developed in small fish for the needs of genomic exploration in sarcopenia.

Animal models of sarcopenia

“…Zebrafish were presented as an aging model in 2002 by Gerhard et al who investigated the process of zebrafish aging and later demonstrated that it is comparable to human aging and suitable to study age‐dependent changes in musculoskeletal function (Gerhard, 2003; Gerhard & Cheng, 2002; Gerhard et al, 2002). Zebrafish as a model for aging has also been supported by the work of Kishi et al (Kishi, 2004; Kishi et al, 2003) The ease of care, prolific breeding, easy genetic manipulability, and ability to readily absorb drugs through their water make the zebrafish an attractive model to work with (Daya, Donaka, & Karasik, 2020; Maves, 2014; Volpatti et al, 2020). Additionally, zebrafish skeletal muscle makes up a large portion of the fish trunk and has a high degree of similarity with human muscle, including the presence of satellite‐like cells for muscle repair and regeneration (Gurevich et al, 2016; Hollway et al, 2007).…”

“…Zebrafish were presented as an aging model in 2002 by Gerhard et al who investigated the process of zebrafish aging and later demonstrated that it is comparable to human aging and suitable to study age-dependent changes in musculoskeletal function (Gerhard, 2003;. Zebrafish as a model for aging has also been supported by the work of Kishi et al (Kishi, 2004;Kishi et al, 2003) The ease of care, prolific breeding, easy genetic manipulability, and ability to readily absorb drugs through their water make the zebrafish an attractive model to work with (Daya, Donaka, & Karasik, 2020;Maves, 2014;Volpatti et al, 2020).…”

The Potential of Calorie Restriction and Calorie Restriction Mimetics in Delaying Aging: Focus on Experimental Models

“…Widely employed in developmental studies, the zebrafish is increasingly used in aging research, due to its relative short life-span (2–3 years), and based on the evidence that it shows hallmarks of gradual senescence, such as spinal curvature, muscle degeneration, and reduced physical ability [ 90 , 91 , 92 ]. Interestingly, recent research shows that zebrafish can be exploited for the investigation of neurodegenerative pathologies as Alzheimer disease, Parkinson disease [ 93 ], but also osteoporosis, sarcopenia [ 94 ], and age-dependent trainability [ 95 ].…”

A Multifactorial Approach for Sarcopenia Assessment: A Literature Review

“…To treat muscle wasting diseases such as sarcopenia, researchers extensively studied the functions and structural properties of MSTN (encoded by the MSTN gene). MSTN is the most studied member of the TGF-β family and a negative regulator of skeletal muscle growth and development [ 54 ]. Another study suggested that the amount of PR domain-containing 16 (PRDM16) gene could regulate brown adipose tissue, white adipose tissue, and muscle cell metabolism [ 55 ].…”