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Slow skeletal muscle troponin T (TNNT1) pre-messenger RNA alternative splicing (AS) provides transcript diversity and increases the variety of proteins the gene encodes. Here, we identified three major TNNT1 splicing patterns (AS1–3), quantified their expression in the vastus lateralis muscle of older adults, and demonstrated that resistance training modifies their relative abundance; specifically, upregulating AS1 and downregulating AS2 and AS3. In addition, abundance of TNNT1 AS2 correlated negatively with single muscle fiber–specific force after resistance training, while abundance of AS1 correlated negatively with Vmax. We propose that TNNT1 AS1, AS2 and the AS1/AS2 ratio are potential quantitative biomarkers of skeletal muscle adaptation to resistance training in older adults, and that their profile reflects enhanced single fiber muscle force in the absence of significant increases in fiber cross-sectional area. [ABSTRACT FROM PUBLISHER]

Loss of muscle mass and force with age leads to fall risk, mobility impairment, and reduced quality of life. This article shows that BDA-410, a calpain inhibitor, induced loss of body weight and fat but not lean mass or skeletal muscle proteins in a cohort of sedentary 23-month-old mice. Food and water intake and locomotor activity were not modified, whereas BDA-410 treatment decreased intramyocellular lipid and perigonadal fat, increased serum nonesterified fatty acids, and upregulated the genes mediating lipolysis and oxidation, lean phenotype, muscle contraction, muscle transcription regulation, and oxidative stress response. This finding is consistent with our recent report that lipid accumulation in skeletal myofibers is significantly correlated with slower fiber-contraction kinetics and diminished power in obese older adult mice. A proteomic analysis and immunoblot showed downregulation of the phosphatase PPP1R12B, which increases phosphorylated myosin half-life and modulates the calcium sensitivity of the contractile apparatus. This study demonstrates that BDA-410 exerts a beneficial effect on skeletal muscle contractility through new, alternative mechanisms, including enhanced lipolysis, upregulation of "lean phenotype-related genes," downregulation of the PP1R12B phosphatase, and enhanced excitation-contraction coupling. This single compound holds promise for treating age-dependent decline in muscle composition and strength. [ABSTRACT FROM AUTHOR]

Background: Evidence implicates the amount and location of fat in aging-related loss of muscle function; however, whether intramyocellular lipids affect muscle contractile capacity is unknown.Methods: We compared both in vivo knee extensor muscle strength, power, and quality and in vitro mechanical properties of vastus lateralis single-muscle fibers between normal weight (NW) and obese older adults and determined the relationship between muscle lipid content (both intramuscular adipose tissue and intramyocellular lipids) and in vivo and in vitro muscle function in NW and obese individuals.Results: The obese group had a greater percentage of type-I fibers compared to the NW group. The cross-sectional area of type-I fibers was greater in obese compared to NW; however, maximal shortening velocity of type-I fibers in the obese was slower compared to NW. Type-I and type-IIa fibers from obese group produced lower specific force than that of type-I and type-IIa fibers from the NW group. Normalized power was also substantially lower (~50%) in type-I fibers from obese adults. The intramyocellular lipids data showed that total lipid droplet area, number of lipid droplets, and area fraction were about twofold greater in type-I fibers from the obese compared to the NW group. Interestingly, a significant inverse relationship between average number of lipid droplets and single-fiber unloaded shortening velocity, maximal velocity, and specific power was observed in obese participants. Additionally, muscle echointensity correlated with single-fiber specific force.Conclusions: These data indicate that greater intramyocellular lipids are associated with slower myofiber contraction, force, and power development in obese older adults. [ABSTRACT FROM AUTHOR]