Key result
Gsα deficiency increases fatigue resistance in older mice, driven by a fast-to-slow fiber-type switch.
Why the study?
Gsα deficiency in skeletal muscle causes metabolic abnormalities and a fast-to-slow-fiber-type switch, but the adaptive benefit of this switch was unclear.
Does Gsα deficiency in skeletal muscle alter fiber-type composition and fatigue resistance in mice?
Does Gsα deficiency in skeletal muscle alter fiber-type composition and fatigue resistance in mice?
The fast-to-slow fiber-type switch in Gsα-deficient skeletal muscle is an adaptive response that increases fatigue resistance, potentially providing a mechanism to sustain muscle function in aging and metabolic deficiency.
Caution against clinical translation from mice; leaves open whether Gsα signaling modulates human muscle fatigue in aging.
Genetically modified mice with deficiency of the G protein α-subunit (G(s)α) in skeletal muscle showed metabolic abnormality with reduced glucose tolerance, low muscle mass, and low contractile force, along with a fast-to-slow-fiber-type switch (Chen M, Feng HZ, Gupta D, Kelleher J, Dickerson KE, Wang J, Hunt D, Jou W, Gavrilova O, Jin JP, Weinstein LS. Am J Physiol Cell Physiol 296: C930-C940, 2009). Here we investigated a hypothesis that the switching to more slow fibers is an adaptive response with specific benefit. The results showed that, corresponding to the switch of myosin isoforms, the thin-filament regulatory proteins troponin T and troponin I both switched to their slow isoforms in the atrophic soleus muscle of 3-mo-old G(s)α-deficient mice. This fiber-type switch involving coordinated changes of both thick- and thin-myofilament proteins progressed in the G(s)α-deficient soleus muscles of 18- to 24-mo-old mice, as reflected by the expression of solely slow isoforms of myosin and troponin. Compared with age-matched controls, G(s)α-deficient soleus muscles with higher proportion of slow fibers exhibited slower contractile and relaxation kinetics and lower developed force, but significantly increased resistance to fatigue, followed by a better recovery. G(s)α-deficient soleus muscles of neonatal and 3-wk-old mice did not show the increase in slow fibers. Therefore, the fast-to-slow-fiber-type switch in G(s)α deficiency at older ages was likely an adaptive response. The benefit of higher fatigue resistance in adaption to metabolic deficiency and aging provides a mechanism to sustain skeletal muscle function in diabetic patients and elderly individuals.
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Feng et al. (2011) studied G(s)α deficiency and aging in skeletal muscle. G(s)α deficiency vs. Age-matched controls was evaluated on Fatigue resistance and contractile kinetics. G(s)α-deficient soleus muscles in older mice exhibited a fast-to-slow fiber-type switch, resulting in significantly increased resistance to fatigue compared with age-matched controls.
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