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

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.

Evolutionary history and epigenetic regulation of the three paralogous pax7 genes in rainbow trout

“…Such an increase in pax7 expression during the myogenic progression to myotubes has been documented in the closely related species Salmo salar (Bower and Johnston 2010). Similarly, we recently demonstrated that expression of pax3 (another marker of MSCs in mammals) increases during a similar myogenic progression to myotubes in the indeterminately growing giant danio ( Devario aequipinnatus ) (Froehlich et al 2013). In mammalian myogenic cell cultures, pax7 is not expressed in differentiated myotubes, but is maintained in a smaller accompanying population of undifferentiated cells that stops proliferating and returns to a non-proliferating state reminiscent of the quiescent reserve MSCs, which can then reenter the cell cycle, proliferate, and differentiate (Kitzmann et al 1998, Yoshida et al 1998).…”

“…Interestingly, an “unexpected” increase of pax7 expression (a well-accepted marker of quiescent MSCs in mammals) in culture of MSCs under differentiation into myotubes has been documented in a closely related species ( Salmo salar ), possibly reflecting the production of “quiescent reserve cells” (Bower and Johnston 2010). Likewise, we recently demonstrated that MSCs from the indeterminately growing giant danio ( Devario aequipinnatus ) in culture gradually increase pax3 expression (another marker of quiescent MSCs in mammals) during a similar progression to myotubes (Froehlich et al 2013). These data support the hypothesis that the induced expression of these specific paired-box transcription factors (pax3/7) during the culture of MSCs is a common feature of indeterminate growing species and could indicate a high self-renewal of MSCs, a process needed for these cells to continuously contribute to hyperplasia and/or hypertrophy during the lifespan of these fishes (Froehlich et al 2013).…”

“…Likewise, we recently demonstrated that MSCs from the indeterminately growing giant danio ( Devario aequipinnatus ) in culture gradually increase pax3 expression (another marker of quiescent MSCs in mammals) during a similar progression to myotubes (Froehlich et al 2013). These data support the hypothesis that the induced expression of these specific paired-box transcription factors (pax3/7) during the culture of MSCs is a common feature of indeterminate growing species and could indicate a high self-renewal of MSCs, a process needed for these cells to continuously contribute to hyperplasia and/or hypertrophy during the lifespan of these fishes (Froehlich et al 2013). However, very few data exist detailing how the expression of these Pax and MRF transcription factors is regulated in indeterminate growing organisms.…”

Genome-Wide Association Study for Identifying Loci that Affect Fillet Yield, Carcass, and Body Weight Traits in Rainbow Trout (Oncorhynchus mykiss)

“…Rainbow trout exhibit indeterminate growth potential as they have the ability increase both body length and muscle mass throughout adulthood (Johnston et al, 2011). A physiological mechanism unique to indeterminate growers is the ability to maintain a population of myogenic precursor cells with proliferative capacity that then differentiate into myotubes or contribute to nuclear accretion (Mommsen, 2001; Froehlich et al, 2013). Therefore, the continued ability for hyperplasia and hypertrophy in skeletal muscle contributes to the indeterminate growth phenotype (Johnston et al, 2011).…”

The Physiological Effects of Exercise on California Yellowtail (Seriola dorsalis) White Muscle

“…One group of fish whose growth patterns have been widely studied is the teleost. Teleost are bony fish that are marked by their indeterminate growth and phenotypic plasticity (Froehlich et al, 2013;Johnston et al, 2011). Teleost fish are also known for their great capacity for aerobic, sustained swimming, and anaerobic, burst swimming.…”