Human myofiber-enriched aging-induced lncRNA FRAIL1 promotes loss of skeletal muscle function.

The loss of skeletal muscle mass during aging is a significant health concern linked to adverse outcomes in older individuals. Understanding the molecular basis of age-related muscle loss is crucial for developing strategies to combat this debilitating condition. Long noncoding RNAs (lncRNAs) are a largely uncharacterized class of biomolecules that have been implicated in cellular homeostasis and dysfunction across a many tissues and cell types. To identify lncRNAs that might contribute to skeletal muscle aging, we screened for lncRNAs whose expression was altered in vastus lateralis muscle from older compared to young adults. We identified FRAIL1 as an aging-induced lncRNA with high abundance in human skeletal muscle. In healthy young and older adults, skeletal muscle FRAIL1 was increased with age in conjunction with lower muscle function. Forced expression of FRAIL1 in mouse tibialis anterior muscle elicits a dose-dependent reduction in skeletal muscle fiber size that is independent of changes in muscle fiber type. Furthermore, this reduction in muscle size is dependent on an intact region of FRAIL1 that is highly conserved across non-human primates. Unbiased transcriptional and proteomic profiling of the effects of FRAIL1 expression in mouse skeletal muscle revealed widespread changes in mRNA and protein abundance that recapitulate age-related changes in pathways and processes that are known to be altered in aging skeletal muscle. Taken together, these findings shed light on the intricate molecular mechanisms underlying skeletal muscle aging and implicate FRAIL1 in age-related skeletal muscle phenotypes.

Exercise microdosing for skeletal muscle health applications to spaceflight.

Findings from a recent 70-day bedrest investigation suggested intermittent exercise testing in the control group may have served as a partial countermeasure for skeletal muscle size, function, and fiber-type shifts. The purpose of the current study was to investigate the metabolic and skeletal muscle molecular responses to the testing protocols. Eight males (29 ± 2 yr) completed muscle power (6 × 4 s; peak muscle power: 1,369 ± 86 W) and V̇o2max (13 ± 1 min; 3.2 ± 0.2 L/min) tests on specially designed supine cycle ergometers during two separate trials. Blood catecholamines and lactate were measured pre-, immediately post-, and 4-h postexercise. Muscle homogenate and muscle fiber-type-specific [myosin heavy chain (MHC) I and MHC IIa] mRNA levels of exercise markers (myostatin, IκBα, myogenin, MuRF-1, ABRA, RRAD, Fn14, PDK4) and MHC I, IIa, and IIx were measured from vastus lateralis muscle biopsies obtained pre- and 4-h postexercise. The muscle power test altered (P ≤ 0.05) norepinephrine (+124%), epinephrine (+145%), lactate (+300%), and muscle homogenate mRNA (IκBα, myogenin, MuRF-1, RRAD, Fn14). The V̇o2max test altered (P ≤ 0.05) norepinephrine (+1,394%), epinephrine (+1,412%), lactate (+736%), and muscle homogenate mRNA (myostatin, IκBα, myogenin, MuRF-1, ABRA, RRAD, Fn14, PDK4). In general, both tests influenced MHC IIa muscle fibers more than MHC I with respect to the number of genes that responded and the magnitude of response. Both tests also influenced MHC mRNA expression in a muscle fiber-type-specific manner. These findings provide unique insights into the adaptive response of skeletal muscle to small doses of exercise and could help shape exercise dosing for astronauts and Earth-based individuals.NEW & NOTEWORTHY Declines in skeletal muscle health are a concern for astronauts on long-duration spaceflights. The current findings add to the growing body of exercise countermeasures data, suggesting that small doses of specific exercise can be beneficial for certain aspects of skeletal muscle health. This information can be used in conjunction with other components of existing exercise programs for astronauts and might translate to other areas focused on skeletal muscle health (e.g., sports medicine, rehabilitation, aging).

Fast and slow muscle fiber transcriptome dynamics with lifelong endurance exercise.

We investigated fast and slow muscle fiber transcriptome exercise dynamics among three groups of men: lifelong exercisers (LLE, n = 8, 74 ± 1 yr), old healthy nonexercisers (OH, n = 9, 75 ± 1 yr), and young exercisers (YE, n = 8, 25 ± 1 yr). On average, LLE had exercised ∼4 day·wk-1 for ∼8 h·wk-1 over 53 ± 2 years. Muscle biopsies were obtained pre- and 4 h postresistance exercise (3 × 10 knee extensions at 70% 1-RM). Fast and slow fiber size and function were assessed preexercise with fast and slow RNA-seq profiles examined pre- and postexercise. LLE fast fiber size was similar to OH, which was ∼30% smaller than YE (P < 0.05) with contractile function variables among groups, resulting in lower power in LLE (P < 0.05). LLE slow fibers were ∼30% larger and more powerful compared with YE and OH (P < 0.05). At the transcriptome level, fast fibers were more responsive to resistance exercise compared with slow fibers among all three cohorts (P < 0.05). Exercise induced a comprehensive biological response in fast fibers (P < 0.05) including transcription, signaling, skeletal muscle cell differentiation, and metabolism with vast differences among the groups. Fast fibers from YE exhibited a growth and metabolic signature, with LLE being primarily metabolic, and OH showing a strong stress-related response. In slow fibers, only LLE exhibited a biological response to exercise (P < 0.05), which was related to ketone and lipid metabolism. The divergent exercise transcriptome signatures provide novel insight into the molecular regulation in fast and slow fibers with age and exercise and suggest that the ∼5% weekly exercise time commitment of the lifelong exercisers provided a powerful investment for fast and slow muscle fiber metabolic health at the molecular level.NEW & NOTEWORTHY This study provides the first insights into fast and slow muscle fiber transcriptome dynamics with lifelong endurance exercise. The fast fibers were more responsive to exercise with divergent transcriptome signatures among young exercisers (growth and metabolic), lifelong exercisers (metabolic), and old healthy nonexercisers (stress). Only lifelong exercisers had a biological response in slow fibers (metabolic). These data provide novel insights into fast and slow muscle fiber health at the molecular level with age and exercise.

Multitissue responses to exercise: a MoTrPAC feasibility study.

We assessed the feasibility of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) human adult clinical exercise protocols, while also documenting select cardiovascular, metabolic, and molecular responses to these protocols. After phenotyping and familiarization sessions, 20 subjects (25 ± 2 yr, 12 M, 8 W) completed an endurance exercise bout (n = 8, 40 min cycling at 70% V̇o2max), a resistance exercise bout (n = 6, ∼45 min, 3 sets of ∼10 repetition maximum, 8 exercises), or a resting control period (n = 6, 40 min rest). Blood samples were taken before, during, and after (10 min, 2 h, and 3.5 h) exercise or rest for levels of catecholamines, cortisol, glucagon, insulin, glucose, free fatty acids, and lactate. Heart rate was recorded throughout exercise (or rest). Skeletal muscle (vastus lateralis) and adipose (periumbilical) biopsies were taken before and ∼4 h following exercise or rest for mRNA levels of genes related to energy metabolism, growth, angiogenesis, and circadian processes. Coordination of the timing of procedural components (e.g., local anesthetic delivery, biopsy incisions, tumescent delivery, intravenous line flushes, sample collection and processing, exercise transitions, and team dynamics) was reasonable to orchestrate while considering subject burden and scientific objectives. The cardiovascular and metabolic alterations reflected a dynamic and unique response to endurance and resistance exercise, whereas skeletal muscle was transcriptionally more responsive than adipose 4 h postexercise. In summary, the current report provides the first evidence of protocol execution and feasibility of key components of the MoTrPAC human adult clinical exercise protocols. Scientists should consider designing exercise studies in various populations to interface with the MoTrPAC protocols and DataHub.NEW & NOTEWORTHY This study highlights the feasibility of key aspects of the MoTrPAC adult human clinical protocols. This initial preview of what can be expected from acute exercise trial data from MoTrPAC provides an impetus for scientists to design exercise studies to interlace with the rich phenotypic and -omics data that will populate the MoTrPAC DataHub at the completion of the parent protocol.

Acute responsiveness to single leg cycling in adults with obesity.

Obesity is associated with several skeletal muscle impairments which can be improved through an aerobic exercise prescription. The possibility that exercise responsiveness is diminished in people with obesity has been suggested but not well-studied. The purpose of this study was to investigate how obesity influences acute exercise responsiveness in skeletal muscle and circulating amino metabolites. Non-obese (NO; n = 19; 10F/9M; BMI = 25.1 ± 2.8 kg/m2 ) and Obese (O; n = 21; 14F/7M; BMI = 37.3 ± 4.6 kg/m2 ) adults performed 30 min of single-leg cycling at 70% of VO2 peak. 13 C6 -Phenylalanine was administered intravenously for muscle protein synthesis measurements. Serial muscle biopsies (vastus lateralis) were collected before exercise and 3.5- and 6.5-h post-exercise to measure protein synthesis and gene expression. Targeted plasma metabolomics was used to quantitate amino metabolites before and 30 and 90 min after exercise. The exercise-induced fold change in mixed muscle protein synthesis trended (p = 0.058) higher in NO (1.28 ± 0.54-fold) compared to O (0.95 ± 0.42-fold) and was inversely related to BMI (R2  = 0.140, p = 0.027). RNA sequencing revealed 331 and 280 genes that were differentially expressed after exercise in NO and O, respectively. Gene set enrichment analysis showed O had six blunted pathways related to metabolism, cell to cell communication, and protein turnover after exercise. The circulating amine response further highlighted dysregulations related to protein synthesis and metabolism in adults with obesity at the basal state and in response to the exercise bout. Collectively, these data highlight several unique pathways in individuals with obesity that resulted in a modestly blunted exercise response.

Sex Differences in Performance and Depth of Field in the United States Olympic Trials.

ABSTRACT: Jobe, TK, Shaffer, HN, Doci, CL, and Gries, KJ. Sex differences in performance and depth of field in the United States Olympic trials. J Strength Cond Res 36(11): 3122-3129, 2022-Recently, there has been an increased discussion on the role of sex as a variable in human performance. Although there likely remains sociological factors, we can estimate biological sex differences in human performance by comparing finishing times in elite men and women. We sought to determine the effect of sex on running and swimming velocity and depth of field in events of varying lengths in the previous 25 years. Finishing times from United States Olympic trials in running events (100 m to marathon) and freestyle swimming (50-1,500 m) from 1996 to 2021 were collected. Sex differences in velocity were calculated for each year (trends), place (first through seventh), and depth of field (nth place/first place). Significance was set at p ≤ 0.05. Men were 9-13% faster than women in all running events (p ≤ 0.05). The 100-m dash (9%) had the lowest sex difference compared with races of longer distance (p ≤ 0.05). In swimming, men were faster in all events (6-12%, p ≤ 0.05), in which sex differences generally decreased with longer distances. Depth of field was similar between men and women in all running and swimming events. No differences in the analyzed variables were observed from 1996 to 2021. These data suggest that elite men are 9% faster in the 100 m compared with running races of longer distances (~12%). Sex differences in swimmers tended to get smaller as duration increased. Although participation and other sociological factors in these events may play a role, these sex differences warrant further discussion on the role of sex in athletic competition.

A Randomized Trial of the Effects of Dietary n3-PUFAs on Skeletal Muscle Function and Acute Exercise Response in Healthy Older Adults.

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.

Impact of obesity on the molecular response to a single bout of exercise in a preliminary human cohort.

OBJECTIVE: The health benefits of exercise are well documented, but several exercise-response parameters are attenuated in individuals with obesity. The goal of this pilot study was to identify molecular mechanisms that may influence exercise response with obesity. METHODS: A multi-omics comparison of the transcriptome, proteome, and phosphoproteome in muscle from a preliminary cohort of lean individuals (n = 4) and individuals with obesity (n = 4) was performed, before and after a single bout of 30 minutes of unilateral cycling at 70% maximal oxygen uptake (VO2 peak). Mass spectrometry and RNA sequencing were used to interrogate the proteome, phosphoproteome, and transcriptome from muscle biopsy tissue. RESULTS: The main findings are that individuals with obesity exhibited transcriptional and proteomic signatures consistent with reduced mitochondrial function, protein synthesis, and glycogen synthesis. Furthermore, individuals with obesity demonstrated markedly different transcriptional, proteomic, and phosphoproteomic responses to exercise, particularly biosynthetic pathways of glycogen synthesis and protein synthesis. Casein kinase II subunit alpha and glycogen synthase kinase-3ß signaling was identified as exercise-response pathways that were notably altered by obesity. CONCLUSIONS: Opportunities to enhance exercise responsiveness by targeting specific molecular pathways that are disrupted in skeletal muscle from individuals with obesity await a better understanding of the precise molecular mechanisms that may limit exercise-response pathways in obesity.

The Aging Athlete: Paradigm of Healthy Aging.

The Exercise Boom of the 1970's resulted in the adoption of habitual exercise in a significant portion of the population. Many of these individuals are defying the cultural norms by remaining physically active and competing at a high level in their later years. The juxtaposition between masters athletes and non-exercisers demonstrate the importance of remaining physically active throughout the lifespan on physiological systems related to healthspan (years of healthy living). This includes ~50% improved maximal aerobic capacity (VO2max) and enhanced skeletal muscle health (size, function, as well as metabolic and communicative properties) compared to non-exercisers at a similar age. By taking a reductionist approach to VO2max and skeletal muscle health, we can gain insight into how aging and habitual exercise affects the aging process. Collectively, this review provides a physiological basis for the elite performances seen in masters athletes, as well as the health implications of lifelong exercise with a focus on VO2max, skeletal muscle metabolic fitness, whole muscle size and function, single muscle fiber physiology, and communicative properties of skeletal muscle. This review has significant public health implications due to the potent health benefits of habitual exercise across the lifespan.

Muscle-derived factors influencing bone metabolism.

A significant amount of attention has been brought to the endocrine-like function of skeletal muscle on various tissues, particularly with bone. Several lines of investigation indicate that the physiology of both bone and muscle systems may be regulated by a given stimulus, such as exercise, aging, and inactivity. Moreover, emerging evidence indicates that bone is heavily influenced by soluble factors derived from skeletal muscle (i.e., muscle-to-bone communication). The purpose of this review is to discuss the regulation of bone remodeling (formation and/or resorption) through skeletal muscle-derived cytokines (hereafter myokines) including the anti-inflammatory cytokine METRNL and pro-inflammatory cytokines (e.g., TNF-α, IL-6, FGF-2 and others). Our goal is to highlight possible therapeutic opportunities to improve muscle and bone health in aging.

Skeletal muscle mitochondrial dysfunction and muscle and whole body functional deficits in cancer patients with weight loss.

Reductions in skeletal muscle mass and function are often reported in patients with cancer-associated weight loss and are associated with reduced quality of life, impaired treatment tolerance, and increased mortality. Although cellular changes, including altered mitochondrial function, have been reported in animals, such changes have been incompletely characterized in humans with cancer. Whole body and skeletal muscle physical function, skeletal muscle mitochondrial function, and whole body protein turnover were assessed in eight patients with cancer-associated weight loss (10.1 ± 4.2% body weight over 6-12 mo) and 19 age-, sex-, and body mass index (BMI)-matched healthy controls to characterize skeletal muscle changes at the whole body, muscle, and cellular level. Potential pathways involved in cancer-induced alterations in metabolism and mitochondrial function were explored by interrogating skeletal muscle and plasma metabolomes. Despite similar lean mass compared with control participants, patients with cancer exhibited reduced habitual physical activity (57% fewer daily steps), cardiorespiratory fitness [22% lower V̇o2peak (mL/kg/min)] and leg strength (35% lower isokinetic knee extensor strength), and greater leg neuromuscular fatigue (36% greater decline in knee extensor torque). Concomitant with these functional declines, patients with cancer had lower mitochondrial oxidative capacity [25% lower State 3 O2 flux (pmol/s/mg tissue)] and ATP production [23% lower State 3 ATP production (pmol/s/mg tissue)] and alterations in phospholipid metabolite profiles indicative of mitochondrial abnormalities. Whole body protein turnover was unchanged. These findings demonstrate mitochondrial abnormalities concomitant with whole body and skeletal muscle functional derangements associated with human cancer, supporting future work studying the role of mitochondria in the muscle deficits associated with cancer.NEW & NOTEWORTHY To our knowledge, this is the first study to suggest that skeletal muscle mitochondrial deficits are associated with cancer-associated weight loss in humans. Mitochondrial deficits were concurrent with reductions in whole body and skeletal muscle functional capacity. Whether mitochondrial deficits are causal or secondary to cancer-associated weight loss and functional deficits remains to be determined, but this study supports further exploration of mitochondria as a driver of cancer-associated losses in muscle mass and function.

Single muscle fibre contractile characteristics with lifelong endurance exercise.

KEY POINTS: A hallmark trait of ageing skeletal muscle health is a reduction in size and function, which is most pronounced in the fast muscle fibres. 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. 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). Limited benefits with lifelong endurance exercise were noted in the fast muscle fibres. These findings suggest that additional exercise modalities (e.g. resistance exercise) or other therapeutic interventions are needed to target fast muscle fibres with age. ABSTRACT: We investigated single muscle fibre size and contractile function among three groups of men: lifelong exercisers (LLE) (n = 21, 74 ± 4 years), old healthy non-exercisers (OH) (n = 10, 75 ± 2 years) and young exercisers (YE) (n = 10, 25 ± 1 years). On average, LLE had exercised ∼5 days week-1 for ∼7 h week-1 over the past 53 ± 6 years. LLE were subdivided based on lifelong exercise intensity into performance (LLE-P) (n = 14) and fitness (LLE-F) (n = 7). Muscle biopsies (vastus lateralis) were examined for myosin heavy chain (MHC) slow (MHC I) and fast (MHC IIa) fibre size and function (strength, speed, power). LLE MHC I size (7624 ± 2765 µm2 ) was 25-40% larger (P < 0.001) than YE (6106 ± 1710 µm2 ) and OH (5476 ± 2467 µm2 ). LLE MHC I fibres were ∼20% stronger, ∼10% faster and ∼30% more powerful than YE and OH (P < 0.05). By contrast, LLE MHC IIa size (6466 ± 2659 µm2 ) was similar to OH (6237 ± 2525 µm2 ; P = 0.854), with both groups ∼20% smaller (P < 0.001) than YE (7860 ± 1930 µm2 ). MHC IIa contractile function was variable across groups, with a hierarchical pattern (OH > LLE > YE; P < 0.05) in normalized power among OH (16.7 ± 6.4 W L-1 ), LLE (13.9 ± 4.5 W L-1 ) and YE (12.4 ± 3.5 W L-1 ). The LLE-P and LLE-F had similar single fibre profiles with MHC I power driven by speed (LLE-P) or force (LLE-F), suggesting exercise intensity impacted slow muscle fibre mechanics. These data suggest that lifelong endurance exercise benefited slow muscle fibre size and function. Comparable fast fibre characteristics between LLE and OH, regardless of training intensity, suggest other exercise modes (e.g. resistance training) or myotherapeutics may be necessary to preserve fast muscle fibre size and performance with age.

Adipose tissue macrophage populations and inflammation are associated with systemic inflammation and insulin resistance in obesity.

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 nondiabetic 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 ß 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.NEW AND NOTEWORTHY Adipose inflammation is proposed to be at the nexus of the systemic inflammation and metabolic derangements associated with obesity. The present study provides evidence to support adipose inflammation as a central feature of the pathophysiology of obesity. Adipose inflammation is associated with systemic and peripheral metabolic derangements, including increased systemic inflammation, reduced insulin sensitivity, and reduced skeletal muscle mitochondrial respiration.

Low-dose aspirin and COX inhibition in human skeletal muscle.

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 after exercise. Skeletal muscle biopsies (vastus lateralis) were taken from eight individuals [4 men, 4 women; 25 ± 1 yr; 81.4 ± 3.4 kg; maximal oxygen consumption (V̇o2max): 3.33 ± 0.21 L/min] before and 3.5 h after 40 min of cycling at 70% of V̇o2max 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 after a low (10 µM; typical oral dose: 75-325 mg) or standard (100 µM; typical oral dose: 975-1,000 mg) 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 PGE2 suppression 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 who chronically consume low-dose aspirin.NEW & NOTEWORTHY This study demonstrated that even low-dose aspirin concentrations can significantly reduce the prostaglandin (PG)E2/cyclooxygenase (COX) pathway activity in human skeletal muscle and this effect is not altered during the recovery period following aerobic exercise. These findings are noteworthy since aspirin is one of the most commonly consumed drugs in the world and nonaspirin COX-inhibiting drugs have been shown to regulate skeletal muscle health in sedentary and exercise-training individuals.

Single-muscle fiber contractile properties in lifelong aerobic exercising women.

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.

Cardiovascular and skeletal muscle health with lifelong exercise.

The purpose of this study was to examine the effects of aerobic lifelong exercise (LLE) on maximum oxygen consumption (V̇o2max) and skeletal muscle metabolic fitness in trained women ( n = 7, 72 ± 2 yr) and men ( n = 21, 74 ± 1 yr) and compare them to old, healthy nonexercisers (OH; women: n = 10, 75 ± 1 yr; men: n = 10, 75 ± 1 yr) and young exercisers (YE; women: n = 10, 25 ± 1 yr; men: n = 10, 25 ± 1 yr). LLE men 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 5 day/wk for 7 h/wk over the past 52 ± 1 yr. Each subject performed a maximal cycle test to assess V̇o2max and had a vastus lateralis muscle biopsy to examine capillarization and metabolic enzymes [citrate synthase, ß-hydroxyacyl-CoA dehydrogenase (ß-HAD), and glycogen phosphorylase]. V̇o2max had a hierarchical pattern (YE > LLE > OH, P < 0.05) for women (44 ± 2 > 26 ± 2 > 18 ± 1 ml·kg-1·min-1) and men (53 ± 3 > 34 ± 1 > 22 ± 1 ml·kg-1·min-1) and was greater ( P < 0.05) in LLE-P (38 ± 1 ml·kg-1·min-1) than LLE-F (27 ± 2 ml·kg-1·min-1). LLE men regardless of intensity and women had similar capillarization and aerobic enzyme activity (citrate synthase and ß-HAD) as YE, which were 20%-90% greater ( P < 0.05) than OH. In summary, these data show a substantial V̇o2max benefit with LLE that tracked similarly between the sexes, with further enhancement in performance-trained men. 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 be easier to maintain with lifelong aerobic exercise than more central aspects of the cardiovascular system. NEW & NOTEWORTHY Lifelong exercise (LLE) is a relatively new and evolving area of study with information especially limited in women and individuals with varying exercise intensity habits. These data show a substantial maximal oxygen consumption benefit with LLE that tracked similarly between the sexes. Our findings contribute to the very limited skeletal muscle biopsy data from LLE women (>70 yr), and similar to men, revealed a preserved metabolic phenotype comparable to young exercisers.