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In a 77-year-old former world-record-holding male marathoner (2:08:33.6), this study sought to investigate the impact of lifelong intensive endurance exercise on cardiac structure, function, and the trajectory of functional capacity (determined by maximal oxygen consumption, V̇ o 2max) throughout the adult lifespan. As a competitive runner, our athlete (DC) reported performing up to 150–300 miles/wk of moderate-to-vigorous exercise and sustained 10–15 h/wk of endurance exercise after retirement from competition. DC underwent maximal cardiopulmonary exercise testing in 1970 (aged 27 yr), 1991 (aged 49 yr), and 2020 (aged 77 yr) to determine V̇ o 2max. At his evaluation in 2020, DC also underwent comprehensive cardiac assessments including resting echocardiography, and resting and exercise cardiac magnetic resonance to quantify cardiac structure and function at rest and during peak supine exercise. DC's V̇ o 2max showed minimal change from 27 yr (69.7 mL/kg/min) to 49 yr (68.1 mL/kg/min), although it eventually declined by 36% by the age of 77 yr (43.6 mL/kg/min). DC's V̇ o 2max at 77 yr, was equivalent to the 50th percentile for healthy 20- to 29-yr-old males and 2.4 times the requirement for maintaining functional independence. This was partly due to marked ventricular dilatation (left-ventricular end-diastolic volume: 273 mL), which facilitates a large peak supine exercise stroke volume (200 mL) and cardiac output (22.2 L/min). However, at the age of 78 yr, DC developed palpitations and fatigue and was found to be in atrial fibrillation requiring ablation procedures to revert his heart to sinus rhythm. Overall, this life study of a world champion marathon runner exemplifies the substantial benefits and potential side effects of many decades of intense endurance exercise. NEW & NOTEWORTHY: This life study of a 77-yr-old former world champion marathon runner exemplifies the impact of lifelong high-volume endurance exercise on functional capacity (V̇ o 2max equivalent to a 20- to 29-yr-old), partly due to extreme ventricular remodeling that facilitates a large cardiac output during exercise despite reduced maximal heart rate. Although it is possible that this extreme remodeling may contribute to developing atrial fibrillation, the net benefits of extreme exercise throughout this athlete's lifespan favor increased health span and expected longevity. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) and nitric oxide (NO) have been implicated in the regulation of skeletal muscle glucose uptake during contraction, and there is evidence that they do so via interaction with AMP-activated protein kinase (AMPK). In this study, we tested the hypothesis that ROS and NO regulate skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism. Isolated extensor digitorum longus (EDL) and soleus muscles from mice that expressed a muscle-specific kinase dead AMPK[alpha]2 isoform (AMPK-KD) and wild-type litter mates (WT) were stimulated to contract, and glucose uptake was measured in the presence or absence of the antioxidant N-acetyl-L-cysteine (NAC) or the nitric oxide synthase (NOS) inhibitor [N.sup.G]-monomethyl-L-arginine (L-NMMA). Contraction increased AMPK[alpha]2 activity in WT but not AMPK-KD EDL muscles. However, contraction increased glucose uptake in the EDL and soleus muscles of AMPK-KD and WT mice to a similar extent. In EDL muscles, NAC and L-NMMA prevented contraction-stimulated increases in oxidant levels (dichloroflourescein fluorescence) and NOS activity, respectively, and attenuated contraction-stimulated glucose uptake in both genotypes to a similar extent. In soleus muscles of AMPK-KD and WT mice, NAC prevented contraction-stimulated glucose uptake and L-NMMA had no effect. This is likely attributed to the relative lack of neuronal NOS in the soleus muscles compared with EDL muscles. Contraction increased AMPK[alpha] [Thr.sup.172] phosphorylation in EDL and soleus muscles of WT but not AMPK-KD mice, and this was not affected by NAC or L-NMMA treatment. In conclusion, ROS and NO are involved in regulating skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism. nitric oxide; reactive oxygen species; exercise; metabolism; contraction; glucose uptake doi:10.1152/ajpendo.00239.2009.

Uteroplacental insufficiency has been shown to impair insulin action and glucose homeostasis in adult offspring and may act in part via altered mitochondrial biogenesis and lipid balance in skeletal muscle. Bilateral uterine vessel ligation to induce uteroplacental insufficiency in offspring (Restricted) or sham surgery was performed on day 18 of gestation in rats. To match the litter size of Restricted offspring, a separate cohort of sham litters had litter size reduced to five at birth (Reduced Litter), which also restricted postnatal growth. Remaining litters from sham mothers were unaltered (Control). Offspring were studied at 6 mo of age. In males, both Restricted and Reduced Litter offspring had reduced gastrocnemius PPAR[gamma] coactivator-1[alpha] (PGC1[alpha]) mRNA and protein, and mitochondrial transcription factor A (mtTFA) and cytochrome oxidase (COX) III mRNA (P < 0.05), whereas only Restricted had reduced skeletal muscle COX IV mRNA and protein and glycogen (P < 0.05), despite unaltered glucose tolerance, homeostasis model assessment (HOMA) and intramuscular triglycerides. In females, only gastrocnemius mtTFA mRNA was lower in Reduced Litter offspring (P < 0.05). Furthermore, glucose tolerance was not altered in any female offspring, although HOMA and intramuscular triglycerides increased in Restricted offspring (P < 0.05). It is concluded that restriction of growth due to uteroplacental insufficiency alters skeletal muscle mitochondrial biogenesis and metabolic characteristics, such as glycogen and lipid levels, in a sex-specific manner in the adult rat in the absence of impaired glucose tolerance. Furthermore, an adverse postnatal environment induced by reducing litter size also restricts growth and alters skeletal muscle mitochondrial biogenesis and metabolic characteristics in the adult rat. programming; glucose metabolism; intrauterine growth restriction

The major isoform of nitric oxide synthase (NOS) in skeletal muscle is the splice variant of neuronal NOS, termed nNOS[micro]. Exercise training increases nNOS[micro] protein levels in rat skeletal muscle, but data in humans are conflicting. We performed two studies to determine 1) whether resting nNOS[micro] protein expression is greater in skeletal muscle of 10 endurance-trained athletes compared with 11 sedentary individuals (study 1) and 2) whether intense short-term (10 days) exercise training increases resting nNOS[micro] protein (within whole muscle and also within types I, IIa, and IIx fibers) in eight sedentary individuals (study 2). In study 1, nNOS[micro] protein was ~60% higher (P < 0.05) in endurance-trained athletes compared with the sedentary participants. In study 2, nNOS[micro] protein expression was similar in types I, IIa, and IIx fibers before training. Ten days of intense exercise training significantly (P < 0.05) increased nNOS[micro] protein levels in types I, IIa, and IIx fibers, a finding that was validated by using whole muscle samples. Endothelial NOS and inducible NOS protein were barely detectable in the skeletal muscle samples. In conclusion, nNOS[micro] protein expression is greater in endurance-trained individuals when compared with sedentary individuals. Ten days of intense exercise is also sufficient to increase nNOS[micro] expression in untrained individuals, due to uniform increases of nNOS[micro] within types I, IIa, and IIx fibers. nitric oxide; nitric oxide synthase; immunohistochemistry