Higher expression of denervation-responsive genes is negatively associated with muscle volume and performance traits in the study of muscle, mobility, and aging (SOMMA).

With aging skeletal muscle fibers undergo repeating cycles of denervation and reinnervation. In approximately the 8th decade of life reinnervation no longer keeps pace, resulting in the accumulation of persistently denervated muscle fibers that in turn cause an acceleration of muscle dysfunction. The significance of denervation in important clinical outcomes with aging is poorly studied. The Study of Muscle, Mobility, and Aging (SOMMA) is a large cohort study with the primary objective to assess how aging muscle biology impacts clinically important traits. Using transcriptomics data from vastus lateralis muscle biopsies in 575 participants we have selected 49 denervation-responsive genes to provide insights to the burden of denervation in SOMMA, to test the hypothesis that greater expression of denervation-responsive genes negatively associates with SOMMA participant traits that included time to walk 400 meters, fitness (VO2peak), maximal mitochondrial respiration, muscle mass and volume, and leg muscle strength and power. Consistent with our hypothesis, increased transcript levels of: a calciumdependent intercellular adhesion glycoprotein (CDH15), acetylcholine receptor subunits (CHRNA1, CHRND, CHRNE), a glycoprotein promoting reinnervation (NCAM1), a transcription factor regulating aspects of muscle organization (RUNX1), and a sodium channel (SCN5A) were each negatively associated with at least 3 of these traits. VO2peak and maximal respiration had the strongest negative associations with 15 and 19 denervation-responsive genes, respectively. In conclusion, the abundance of denervationresponsive gene transcripts is a significant determinant of muscle and mobility outcomes in aging humans, supporting the imperative to identify new treatment strategies to restore innervation in advanced age.

Assessing exogenous carbohydrate intake needed to optimize human endurance performance across sex: insights from modeling runners pursuing a sub-2-h marathon.

Carbohydrate (CHO) availability sustains high metabolic demands during prolonged exercise. The adequacy of current CHO intake recommendations, 30-90 g·h-1 dependent on CHO mixture and tolerability, to support elite marathon performance is unclear. We sought to scrutinize the current upper limit recommendation for exogenous CHO intake to support modeled sub-2-h marathon (S2M) attempts across elite male and female runners. Male and female runners (n = 120 each) were modeled from published literature with reference characteristics necessary to complete a S2M (e.g., body mass and running economy). Completion of a S2M was considered across a range of respiratory exchange rates, with maximal starting skeletal muscle and liver glycogen content predicted for elite male and female runners. Modeled exogenous CHO bioavailability needed for male and female runners were 93 ± 26 and 108 ± 22 g·h-1, respectively (P < 0.0001, d = 0.61). Without exogenous CHO, males were modeled to deplete glycogen in 84 ± 7 min, females in 71 ± 5 min (P < 0.0001, d = 2.21) despite higher estimated CHO oxidation rates in males (5.1 ± 0.5 g·h-1) than females (4.4 ± 0.5 g·h-1; P < 0.0001, d = 1.47). Exogenous CHO intakes ≤ 90 g·h-1 are insufficient for 65% of modeled runners attempting a S2M. Current recommendations to support marathon performance appear inadequate for elite marathon runners but may be more suitable for male runners in pursuit of a S2M (56 of 120) than female runners (28 of 120).NEW & NOTEWORTHY This study scrutinizes the upper limit of exogenous carbohydrate (CHO) recommendations for elite male and female marathoners by modeling sex-specific needs across an extreme metabolic challenge lasting ∼2 h, a sub-2-h marathon. Contemporary nutritional guidelines to optimize marathon performance appear inadequate for most elite marathon runners but appear more appropriate for males over their female counterparts. Future research examining possible benefits of exogenous CHO intakes > 90 g·h-1 should prioritize female athlete study inclusion.

Higher Expression of Denervation-responsive Genes is Negatively Associated with Muscle Volume and Performance Traits in the Study of Muscle, Mobility and Aging (SOMMA).

With aging skeletal muscle fibers undergo repeating cycles of denervation and reinnervation. In approximately the 8 th decade of life reinnervation no longer keeps pace, resulting in the accumulation of persistently denervated muscle fibers that in turn cause an acceleration of muscle dysfunction. The significance of denervation in important clinical outcomes with aging is poorly studied. The Study of Muscle, Mobility and Aging (SOMMA) is a large cohort study with the primary objective to assess how aging muscle biology impacts clinically important traits. Using transcriptomics data from vastus lateralis muscle biopsies in 575 participants we have selected 49 denervation-responsive genes to provide insights to the burden of denervation in SOMMA, to test the hypothesis that greater expression of denervation-responsive genes negatively associates with SOMMA participant traits that included time to walk 400 meters, fitness (VO 2peak ), maximal mitochondrial respiration, muscle mass and volume, and leg muscle strength and power. Consistent with our hypothesis, increased transcript levels of: a calcium-dependent intercellular adhesion glycoprotein (CDH15), acetylcholine receptor subunits (Chrna1, Chrnd, Chrne), a glycoprotein promoting reinnervation (NCAM1), a transcription factor regulating aspects of muscle organization (RUNX1), and a sodium channel (SCN5A) were each negatively associated with at least 3 of these traits. VO 2peak and maximal respiration had the strongest negative associations with 15 and 19 denervation-responsive genes, respectively. In conclusion, the abundance of denervation-responsive gene transcripts is a significant determinant of muscle and mobility outcomes in aging humans, supporting the imperative to identify new treatment strategies to restore innervation in advanced age.