Frequently contracting muscles that support the body often consist of a high number of slow (type I) oxidative motor units. These slow motor units undergo more rapid atrophy than the fast (type II) motor units during prolonged periods of unloading. The atrophy of slow motor units is associated with a decrease in maximum tetanic force but an increase in maximum shortening velocity. This increase in velocity is linked to the expression of the fast myosin isoform in these fibers. In space medicine, it is crucial to design exercise programs that minimize such phenotypic changes during extended space flights.

The figure labeled 12.21 illustrates the fundamental molecular signaling pathways involved in contributing to net protein synthesis (A) and mitochondrial biogenesis (B) in skeletal muscle in response to exercise. These pathways include AKT (a serine/threonine-specific protein kinase), AMPK (5' adenosine monophosphate–activated protein kinase), ATP (adenosine triphosphate), CaM kinase (Ca++/calmodulin-dependent protein kinase), CREB (cAMP response element binding protein), ERRα (estrogen-related receptor-alpha), FoxO (forkhead box O class of transcription factors), FoxO-P (phosphorylated FoxO), Glut-4 (glucose transporter type 4), HDAC5 (histone deacetylase 5), IGF-1 (insulin-like growth factor 1), MEF2 (myocyte enhancer factor 2), mTOR (mammalian target of rapamycin), Nrf1, Nrf2, and Nrf2α (nuclear respiratory factors 1, 2, and 2α), PGC-1α (peroxisome proliferator-activated receptor γ coactivator 1α), PI3K (phosphatidylinositol-3-kinase), and Tn I (troponin I).
Muscles that frequently contract to support the body typically have a high number of slow (type I) oxidative motor units. These slow motor units atrophy more rapidly than the fast (type II) motor units during prolonged periods of unloading. This atrophy of slow motor units is associated with a decrease in maximal tetanic force but also an increase in maximal shortening velocity. The increase in velocity is correlated with expression of the fast myosin isoform in these fibers. An important aspect of space medicine is the design of exercise programs that minimize such phenotypic changes during prolonged space flight.
• Fig. 12.21. Basic molecular signaling pathways involved in contributing to net protein synthesis (A) and mitochondrial biogenesis (B) in skeletal muscle in response to exercise. AKT, a serine/threonine-specific protein kinase (protein kinase B); AMPK, 5′ adenosine monophosphate–activated protein kinase; ATP, adenosine triphosphate; CaM kinase, Ca++/calmodulin-dependent protein kinase; CREB, cAMP response element binding protein; ERRα, estrogen-related receptor-α; FoxO, forkhead box O class of transcription factors; FoxO-P, phosphorylated FoxO; Glut-4, glucose transporter type 4; HDAC5, histone deacetylase 5; IGF-1, insulin-like growth factor 1; MEF2, myocyte enhancer factor 2; mTOR, mammalian target of rapamycin; Nrf1, Nrf2, and Nrf2α, nuclear respiratory factors 1, 2, and 2α; PGC-1α, peroxisome proliferator-activated receptor γ coactivator 1α; PI3K, phosphatidylinositol-3-kinase; Tn I, troponin I. (A, From Sandri M, et al. PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. PNAS. 2006;103:16260-16265. B, From Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab. 2005;1:361-370.)