Sarcopenia and piscines: the case for indeterminate-growing fish as unique genetic model organisms in aging and longevity research

Jacob M Froehlich,Peggy R Biga,Nicholas J Galt,Zachary G Fowler,Daniel L Smith Jr

doi:10.3389/fgene.2013.00159

Abstract

Sarcopenia and dynapenia pose significant problems for the aged, especially as life expectancy rises in developed countries. Current therapies are marginally efficacious at best, and barriers to breakthroughs in treatment may result from currently employed model organisms. Here, we argue that the use of indeterminate-growing teleost fish in skeletal muscle aging research may lead to therapeutic advancements not possible with current mammalian models. Evidence from a comparative approach utilizing the subfamily Danioninae suggests that the indeterminate growth paradigm of many teleosts arises from adult muscle stem cells with greater proliferative capacity, even in spite of smaller progenitor populations. We hypothesize that paired-box transcription factors, Pax3/7, are involved with this enhanced self-renewal and that prolonged expression of these factors may allow some fish species to escape, or at least forestall, sarcopenia/dynapenia. Future research efforts should focus on the experimental validation of these genes as key factors in indeterminate growth, both in the context of muscle stem cell proliferation and in prevention of skeletal muscle senescence.

Highlights

As the world’s population grows past seven billion, the incidence of sarcopenia and dynapenia is expected to rise
This marked rise in elderly persons and subsequent diagnoses of sarcopenia and dynapenia pose a significant challenge to aging researchers (Clark and Manini, 2008, 2010), as the need for effective treatments for these conditions will be of utmost importance
While clinicians have long relied on improved nutrition, specific types of exercise, and management of comorbidities, there is much agreement that interventions at the level of the adult skeletal muscle stem cell, the myosatellite cell (MSC), are warranted, but badly needed (Machida and Narusawa, 2006; Jang et al, 2011; Thornell, 2011; Ma et al, 2012; Pallafacchina et al, 2012; Walston, 2012)

Summary

INTRODUCTION

As the world’s population grows past seven billion, the incidence of sarcopenia and dynapenia is expected to rise. Nearly 87 million persons in the United States will be over the age of 65 by the year 2050 (Federal Interagency Forum on Aging-Related Statistics, 2008) This marked rise in elderly persons and subsequent diagnoses of sarcopenia and dynapenia pose a significant challenge to aging researchers (Clark and Manini, 2008, 2010), as the need for effective treatments (both in terms of cost and therapeutic value) for these conditions will be of utmost importance. While clinicians have long relied on improved nutrition, specific types of exercise (whether that be simple increases in activity or targeted strength training), and management of comorbidities, there is much agreement that interventions at the level of the adult skeletal muscle stem cell, the myosatellite cell (MSC), are warranted, but badly needed (Machida and Narusawa, 2006; Jang et al, 2011; Thornell, 2011; Ma et al, 2012; Pallafacchina et al, 2012; Walston, 2012). No matter if the mouse is of inbred, outbred, crossed, or transgenic origin, it is still a mouse, and increases in lifespan have been achieved, these extensions are still accompanied by marked senescence at some point, accompanied with marked sarcopenia/dynapenia and not without invasive genetic interventions

Indeterminate teleosts as aging models

CONCLUSION

Findings

Medium danionins Large danionins