The purpose of this study was to examine the effects of lifelong aerobic exercise (LLE) on VOmax and skeletal muscle metabolic fitness in trained females (n=7, 72±2y) and males (n=21, 74±1y), and compare them to old healthy non-exercisers (OH; females: n=10, 75±1y; males: n=10, 75±1y), and young exercisers (YE; females: n=10, 25±1y; males: n=10, 25±1y). LLE males were further subdivided based on intensity of lifelong exercise and competitive status into performance (LLE-P, n=14) and fitness (LLE-F, n=7). On average, LLE exercised 5d/wk for 7h/wk over the past 52±1y. Each subject performed a maximal cycle test to assess VOmax and had a vastus lateralis muscle biopsy to examine capillarization and metabolic enzymes (citrate synthase, β-HAD, and glycogen phosphorylase). VOmax had a hierarchical pattern (YE>LLE>OH, P<0.05) for females (44±2>26±2>18±1 ml•kg•min) and males (53±3>34±1>22±1 ml•kg•min), and was greater (P<0.05) in LLE-P (38±1 ml•kg•min) than LLE-F (27±2 ml•kg•min). LLE males, regardless of intensity, and females had similar capillarization and aerobic enzyme activity (citrate synthase and β-HAD) as YE, which were 20-90% greater (P<0.05) than OH. In summary, these data show a substantial VOmax benefit with LLE that tracked similarly between the sexes, with further enhancement in performance trained males. For skeletal muscle, 50+ years of aerobic exercise fully preserved capillarization and aerobic enzymes, regardless of intensity. These data suggest that skeletal muscle metabolic fitness may easier to maintain with lifelong aerobic exercise than more central aspects of the cardiovascular system.

support-information-section). Key pointsr A hallmark trait of ageing skeletal muscle health is a reduction in size and function, which is most pronounced in the fast muscle fibres.r We studied older men (74 ± 4 years) with a history of lifelong (>50 years) endurance exercise to examine potential benefits for slow and fast muscle fibre size and contractile function.r Lifelong endurance exercisers had slow muscle fibres that were larger, stronger, faster and more powerful than young exercisers (25 ± 1 years) and age-matched non-exercisers (75 ± 2 years).r Limited benefits with lifelong endurance exercise were noted in the fast muscle fibres. r These findings suggest that additional exercise modalities (e.g. resistance exercise) or other therapeutic interventions are needed to target fast muscle fibres with age.

Obesity is accompanied by numerous systemic and tissue-specific derangements, including systemic inflammation, insulin resistance, and mitochondrial abnormalities in skeletal muscle. Despite growing recognition that adipose tissue dysfunction plays a role in obesity-related disorders, the relationship between adipose tissue inflammation and other pathological features of obesity is not well-understood. We assessed macrophage populations and measured the expression of inflammatory cytokines in abdominal adipose tissue biopsies in 39 non-diabetic adults across a range of body mass indexes (BMI 20.5-45.8 kg/m2). Skeletal muscle biopsies were used to evaluate mitochondrial respiratory capacity, ATP production capacity, coupling, and reactive oxygen species production. Insulin sensitivity (SI) and beta cell responsivity were determined from test meal postprandial glucose, insulin, c-peptide, and triglyceride kinetics. We examined the relationships between adipose tissue inflammatory markers, systemic inflammatory markers, SI, and skeletal muscle mitochondrial physiology. BMI was associated with increased adipose tissue and systemic inflammation, reduced SI, and reduced skeletal muscle mitochondrial oxidative capacity. Adipose-resident macrophage numbers were positively associated with circulating inflammatory markers, including tumor necrosis factor-α (TNFα) and C-reactive protein (CRP). Local adipose tissue inflammation and circulating concentrations of TNFα and CRP were negatively associated with SI, and circulating concentrations of TNFα and CRP were also negatively associated with skeletal muscle oxidative capacity. These results demonstrate that obese humans exhibit increased adipose tissue inflammation concurrently with increased systemic inflammation, reduced insulin sensitivity, and reduced muscle oxidative capacity, and suggest that adipose tissue and systemic inflammation may drive obesity-associated metabolic derangements.

The purpose of this study was to examine the effects of lifelong aerobic exercise on single-muscle fiber performance in trained women (LLE; n = 7, 72 ± 2 yr) by comparing them to old healthy nonexercisers (OH; n = 10, 75 ± 1 yr) and young exercisers (YE; n = 10, 25 ± 1 yr). On average, LLE had exercised ~5 days/wk for ~7 h/wk over the past 48 ± 2 yr. Each subject had a vastus lateralis muscle biopsy to examine myosin heavy chain (MHC) I and IIa single-muscle fiber size and function (strength, speed, power). MHC I fiber size was similar across all three cohorts (YE = 5,178 ± 157, LLE = 4,983 ± 184, OH = 4,902 ± 159 µm2). MHC IIa fiber size decreased ( P < 0.05) 36% with aging (YE = 4,719 ± 164 vs. OH = 3,031 ± 153 µm2), with LLE showing a similar 31% reduction (3,253 ± 189 µm2). LLE had 17% more powerful ( P < 0.05) MHC I fibers and offset the 18% decline in MHC IIa fiber power observed with aging ( P < 0.05). The LLE contractile power was driven by greater strength (+11%, P = 0.056) in MHC I fibers and elevated contractile speed (+12%, P < 0.05) in MHC IIa fibers. These data indicate that lifelong exercise did not benefit MHC I or IIa muscle fiber size. However, LLE had contractile function adaptations that enhanced MHC I fiber power and preserved MHC IIa fiber power through different contractile mechanisms (strength vs. speed). The single-muscle fiber contractile properties observed with lifelong aerobic exercise are unique and provide new insights into aging skeletal muscle plasticity in women at the myocellular level. NEW & NOTEWORTHY This is the first investigation to examine the effects of lifelong exercise on single-muscle fiber physiology in women. Nearly 50 yr of moderate to vigorous aerobic exercise training resulted in enhanced slow-twitch fiber power primarily by increasing force production, whereas fast-twitch fiber power was preserved primarily by increasing contractile speed. These unique muscle fiber power profiles helped offset the effects of fast-twitch fiber atrophy and highlight the benefits of lifelong aerobic exercise for myocellular health.

Skeletal muscle health has been shown to benefit from regular consumption of cyclooxygenase (COX) inhibiting drugs. Aspirin, especially at low doses, is one of the most commonly consumed COX inhibitors, yet investigations of low dose aspirin effects on skeletal muscle are nonexistent. The goal of this study was to examine the efficacy of low dose aspirin on skeletal muscle COX production of the inflammatory regulator prostaglandin (PG) E2 at rest and following exercise. Skeletal muscle biopsies (vastus lateralis) were taken from eight individuals (4M, 4W; 25±1y; 81.4±3.4kg; VO2max: 3.33±0.21L/min) before and 3.5 hours after 40 minutes of cycling at 70% of VO2max for the measurement of ex vivo PGE2 production. Muscle strips were incubated in Krebs-Henseleit buffer (control) or supplemented with one of two aspirin concentrations that reflected blood levels following a low (10µM; typical oral dose: 75-325mg) or standard (100µM; typical oral dose: 975-1000mg) dose. Low (-22±5%) and standard (-28±5%) dose aspirin concentrations both reduced skeletal muscle PGE2 production, independent of exercise (P<0.05). There was no difference in PGE2suppression between the two doses (P>0.05). In summary, low dose aspirin levels are sufficient to inhibit the COX enzyme in skeletal muscle and significantly reduce production of PGE2, a known regulator of skeletal muscle health. Aerobic exercise does not appear to alter the inhibitory efficacy of aspirin. These findings may have implications for the tens of millions of individuals that chronically consume low dose aspirin.

support-information-section). Key points r Healthy older adults exhibit lower cardiorespiratory fitness (V O 2 peak ) than young in the absence of any age-related difference in skeletal muscle mitochondrial capacity, suggesting central haemodynamics plays a larger role in age-related declines inV O 2 peak . r Total physical activity did not differ by age, but moderate-to-vigorous physical activity was lower in older compared to young adults. r Moderate-to-vigorous physical activity is associated withV O 2 peak and muscle oxidative capacity, but physical inactivity cannot entirely explain the age-related reduction inV O 2 peak .

Skeletal muscle is critical for maintaining mobility, independence, and metabolic health in older adults. However, a common feature of aging is the progressive loss of skeletal muscle mass and function, which is often accompanied by mitochondrial impairments, oxidative stress, and insulin resistance. Exercise improves muscle strength, mitochondrial health, and cardiorespiratory fitness, but older adults often exhibit attenuated anabolic responses to acute exercise. Chronic inflammation associated with aging may contribute to this “anabolic resistance” and therapeutic interventions that target inflammation may improve exercise responsiveness. To this end, we conducted a randomized controlled trial to determine the effect of 6 months of dietary omega-3 polyunsaturated fatty acids (n3-PUFA) supplementation on skeletal muscle function (mass, strength), mitochondrial physiology (respiration, ATP production, ROS generation), and acute exercise responsiveness at the level of the muscle (fractional synthesis rate) and the whole-body (amino acid kinetics) in healthy older adults. When compared with a corn oil placebo (n = 33; 71.5 ± 4.8 years), older adults treated with 4 g/day n3-PUFA (n = 30; 71.4 ± 4.5 years) exhibited modest but significant increases in muscle strength (3.1 ± 14.7% increase in placebo vs. 7.5 ± 14.1% increase in n3-PUFA; p = 0.039). These improvements in muscle strength with n3-PUFA supplementation occurred in the absence of any effects on mitochondrial function and a minor attenuation of the acute response to exercise compared to placebo. Together, these data suggest modest benefits of dietary n3-PUFAs to muscle function in healthy older adults. Future studies may elucidate whether n3-PUFA supplementation improves the exercise response in elderly individuals with co-morbidities, such as chronic inflammatory disease or sarcopenia.

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