Auburn Research Day 2021

Bradley A. Ruple 1 ; Joshua S. Godwin 1 ; Paulo H. C. Mesquita 1 ; Shelby C. Osburn 1 ; Christopher G. Vann 1 ; Donald A. Lamb 1 ; Johnathon H. Moore 1 ; Casey L. Sexton 1 ; Darren G. Candow 2 ; Scott C. Forbes 3 ; Kevin W. Huggins 1 ; Andrew D. Frug 1 ; Kaelin C. Young 1,4 ; Andreas N. Kavazis 1 ; Robert A. Seaborne 5 ; Adam P. Sharples 6 ; Michael D. Roberts 1,4 1 Auburn University, AL, USA; 2 Faculty of Kinesiology and Health Studies, University of Regina, SK, CAN; 3 Faculty of Education, Department of Physical Education, Brandon University, MB, CAN; 4 Edward Via College of Osteopathic Medicine, AL, USA; 5 Queen Mary University of London, London, UK; 6 Norwegian School of Sports Sciences, Oslo, NOR B i omed i ca l Resea rch | Gr adua te / Undergr adua te St udent Six Weeks of Resistance Training Elicits Robust Alterations in the Mitochondrial Methylome in Skeletal Muscle of Older, Untrained Men 030

Background: Recent evidence suggests exercise training dynamically alters the skeletal muscle methylome in older participants, and this may be an involved mechanism for myocellular adaptations. However, information is lacking regarding how exercise training affects the mitochondrial methylome. Thus, we sought to determine how six weeks of resistance training affected the skeletal muscle mitochondrial methylome in older men. Methods: Ten older male participants with no structured resistance training experience (65±7 years old, 18.1±1.5 lean body mass index in kg/m2) performed testing batteries prior to and 72 hours following the last bout of resistance training. These batteries consisted of knee extensor strength testing, body composition analyses and a muscle biopsy from the vastus lateralis. Select data from older participants were also compared to college-aged men that were previously trained (22±2 years old, 20.5±1.2 lean body mass index in kg/m2, 6±1 years of prior training, n=8). DNA obtained from biopsies were subjected to targeted methyl-Seq to examine the mitochondrial methylome, and various biochemical assays were performed as follow-up analyses.

Results: On average, the six-week training program increased whole-body lean/soft tissue mass by 1.2% (assessed by DXA) (p=0.017), vastus lateralis thickness by 7.6% (assessed by ultrasound) (p=0.012) and knee extensor peak torque by 16% (p=0.029). Methyl-Seq analysis indicated that, while genes in the nuclear genome were largely not affected by training, mitochondrial DNA (mtDNA) methylation was profoundly affected; specifically, 169 mtDNA sites were hypotmethylated following training. Notably, several of these mitochondrial DNA targets carried a more “youth-like” signature when comparing post-training values in older participants to younger participants. Mitochondrial volume (assessed through citrate synthase activity assays) did not change with training (p=1.00). However, training did increase complex 3 and 4 protein content (p<0.05) as well as numerous H-strand and one L-strand mitochondrial mRNA targets. Conclusions: This is the first study to demonstrate exercise training, resistance training in particular, alters the mitochondrial methylome in human skeletal muscle from older individuals with minimal prior training experience. Moreover, based on our mRNA and Western blot data, these mitochondrial methylome alterations may be an initial cue that signals positive mitochondrial adaptations to occur in response to resistance training in older individuals.

Jennifer L. Robinson; Julio A. Yanes; Meredith A. Reid; Jerry E. Murphy; Jessica N. Busler; Petey W. Mumford; Kaelin C. Young; Zbigniew J. Pietrzkowski; Boris Nemzer; John M. Hunter; Darren T. Beck Edward Via College of Osteopathic Medicine; Auburn University Department of Kinesiology; Auburn University Department of Psychology; Auburn University MRI Research Center B i omed i ca l Resea rch | Med i ca l Facu l t y Neurophysiological Effects of Whole Coffee Cherry Extract in Older Adults with Subjective Cognitive Impairment: A Randomized, Double- Blind, Placebo-Controlled, Cross-Over Pilot Study 031

Bioactive plant-based compounds have shown promise as protective agents across multiple domains including improvements in neurological and psychological measures. Methodological challenges have limited our understanding of the neurophysiological changes associated with phytochemical-rich supplements such as whole coffee cherry extract (WCCE). In the current study, we compared 100mg WCCE to placebo using an acute, randomized, double-blind, within-subject, cross-over design. The primary objective of the study was to determine the neurophysiological and behavioral changes that resulted from acute administration of WCCE. We hypothesized that WCCE would increase brain derived neurotrophic factor (BDNF) and glutamate, while also increasing neurofunctional measures in cognitive brain regions. Furthermore, we expected there to be increased behavioral performance associated with WCCE, as measured by reaction time and

accuracy. Participants underwent 4 neuroimaging scans (pre- and post-WCCE, pre- and post-placebo) to assess neurofunctional/ metabolic outcomes using functional magnetic resonance imaging and magnetic resonance spectroscopy, respectively. Results suggest that WCCE is associated with decreased reaction time and may protect against cognitive errors on tasks of working memory and response inhibition. Behavioral findings were concomitant with neurofunctional changes in structures involved in decision- making and attention. Specifically, we found increased functional connectivity between the anterior cingulate and regions involved in sensory and decision-making networks. Additionally, we observed increased BDNF and increased glutamate/GABA ratio following WCCE administration. These results suggest that WCCE is associated with acute neurophysiological changes supportive of faster reaction time and increased sustained attention.

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