Translational exercise biomedicine最新文献

Objectives: To examine the effect of the NAD⁺ precursor, nicotinic acid (NA), for improving skeletal muscle status in sedentary older people.

Methods: In a double-blind, randomised, placebo-controlled design, 18 sedentary yet otherwise healthy older (65-75 y) males were assigned to 2-weeks of NA (acipimox; 250 mg × 3 daily, n=8) or placebo (PLA, n=10) supplementation. At baseline, and after week 1 and week 2 of supplementation, a battery of functional, metabolic, and molecular readouts were measured.

Results: Resting and submaximal respiratory exchange ratio was lower (p<0.05) after 2 weeks in the NA group only, but maximal aerobic and anaerobic function and glucose handling were unchanged (p>0.05). Bayesian statistical modelling identified that leak, maximal coupled and maximal uncoupled mitochondrial respiratory states, increased over the 2-week supplemental period in the NA group (probability for a positive change (pd) 85.2, 90.8 and 95.9 %, respectively) but not in PLA. Citrate synthase and protein content of complex II (SDHB) and V (ATP5A) electron transport chain (ETC) components increased over the 2-week period in the NA group only (pd 95.1, 74.5 and 82.3 %, respectively). Mitochondrial and myofibrillar protein synthetic rates remained unchanged in both groups. NA intake altered the muscle transcriptome by increasing the expression of gene pathways related to cell adhesion/cytoskeleton organisation and inflammation/immunity and decreasing pathway expression of ETC and aerobic respiration processes. NAD⁺-specific pathways (e.g., de novo NAD⁺ biosynthetic processes) and genes (e.g., NADSYN1) were uniquely regulated by NA.

Conclusions: NA might be an effective strategy for improving ageing muscle mitochondrial health.

Objectives: To determine how the anti-inflammatory actions of interleukin-10 (IL-10) and IL-6 differ across age and physical activity levels.

Methods: Using a cross-sectional design, fasted blood samples were obtained from younger physically inactive (YI: n=10, age: 22.7 ± 3.7 years, BMI: 24.8 ± 4.8 kg/m², <150 min of weekly moderate-to-vigorous physical activity [MVPA]), younger highly active (YA: n=11 varsity cross country running athletes, 20.7 ± 2.7 years, 21.1 ± 1.8 kg/m², >300 min of weekly MVPA), and older highly active (OA: 12, 56.0 ± 10.3 years, 22.8 ± 3.2 kg/m², >300 min of weekly MVPA) individuals and analyzed for leukocyte counts, IL-10 and IL-6-related signaling, and cytokine secretion ex vivo.

Results: Total white blood cells and monocytes were similar between groups (p=0.8) but YA and OA had lower lymphocyte counts than YI (p<0.01). The ability of IL-10 (1 ng/mL) to phosphorylate signal transducer and activator of transcription 3 (STAT3) in CD14 monocytes was greater in YA vs. YI (p<0.03) despite YA having lower IL-10 receptor expression (p<0.01). IL-6 (10 ng/mL) mediated STAT3 phosphorylation in CD4 lymphocytes was higher in OA compared YI (p<0.01), with a similar tendency observed for YA vs. YI (p=0.08). Despite enhanced responsiveness of STAT3 to IL-10/6 in active individuals, the ability of IL-10/6 to inhibit tumor necrosis factor-alpha (TNF-⍺) secretion from lipopolysaccharide-stimulated whole-blood was similar between groups.

Conclusions: Highly active younger and older individuals demonstrate enhanced IL-10- and IL-6-mediated activation of immune cell STAT3. Although the ability of IL-10/6 to inhibit TNF-⍺ secretion appeared unimpacted by activity level, anti-inflammatory cytokine actions were preserved in older active individuals.

Objectives: To investigate the impact of acute energetic stress (acute HIIE and fasting) on ERRγ, PPARβ, NR1D1, NR4A1, and TFEB in human skeletal muscle.

Methods: The current study performed secondary analyses using muscle biopsy samples from two previously published studies: study 1) leg muscle biopsies from nine men and eight women were obtained pre and 3 h following acute high-intensity interval cycling exercise (HIIE); study 2) leg muscle biopsies were obtained from nine men pre-, during, and post-an 8 h fast with or without 2 h of arm ergometer exercise. RT-PCR was performed on samples from each study to determine the mRNA expression of ERRγ, PPARβ, NR1D1, NR4A1, and TFEB. Additionally, we retrieved data from meta-analyzed human muscle gene expression using the publicly available database MetaMex.

Results: PGC-1α (p<0.01, d=1.98) and NR4A1 (p<0.01, d=1.36) mRNA expression significantly increased while TFEB (p≤0.05, d=0.70) decreased following HIIE. Significant decreases in NR4A1 and NR1D1 mRNA expression were observed following an 8 h fast. Our MetaMex analyses revealed significant increases (p<0.05) in PGC-1α and NR4A1 expression following aerobic and resistance exercise, and in PPARβ expression following resistance exercise.

Conclusions: Our data indicate that acute HIIE stimulates increases in NR4A1 and PGC-1α and decreases in TFEB mRNA expression in human skeletal muscle. Additionally, a short term (8 h) fast reduced the mRNA expression of the transcriptional regulators NR4A1 and NR1D1 - potentially as a mechanism of decreasing mitochondrial biogenesis to reduce energy expenditure during a period of restricted energy availability.