Osteoarthritis Across Joint Sites in the Million Veteran Program Cohort: Insights From Electronic Health Records and Military Service History.

Objective: To characterize the relationship between the frequency of idiopathic osteoarthritis (OA) and characteristics including demographics, comorbidities, military service history, and physical health in a veteran population.

Methods: We performed a cohort study in the Million Veteran Program (MVP) using International Classification of Diseases, 9th and 10th revision codes to define the frequency of site-specific OA across 3 joints or unspecified OA in veterans with respect to demographics (eg, age, sex, race and ethnicity), military service data, detailed electronic health records, military branch, and war era.

Results: We validated previous reports of sex- and age-dependent differences in OA frequency, and we identified that unspecified OA was associated with a higher frequency of 16 Deyo-Charlson comorbidities.

Muscle-derived microRNAs correlated with thigh lean mass gains during progressive resistance training in older adults.

Resistance training (RT) remains the most effective treatment for age-related declines in muscle mass. However, many older adults experience attenuated muscle hypertrophy in response to RT when compared with younger adults. This may be attributed to underlying molecular processes that are dysregulated by aging and exacerbated by improperly prescribed RT weekly volume, intensity, and/or frequency doses.

NASA SPRINT exercise program efficacy for vastus lateralis and soleus skeletal muscle health during 70 days of simulated microgravity.

The efficacy of the NASA SPRINT exercise countermeasures program for quadriceps (vastus lateralis) and triceps surae (soleus) skeletal muscle health was investigated during 70 days of simulated microgravity. Individuals completed 6° head-down-tilt bedrest (BR, = 9), bedrest with resistance and aerobic exercise (BRE, = 9), or bedrest with resistance and aerobic exercise and low-dose testosterone (BRE + T, = 8). All groups were periodically tested for muscle ( = 9 times) and aerobic ( = 4 times) power during bedrest.

Effects of aging and lifelong aerobic exercise on expression of innate immune components in skeletal muscle of women.

This study examined the effects of aging and lifelong aerobic exercise on innate immune system components in the skeletal muscle of healthy women in the basal state and after an unaccustomed resistance exercise (RE) challenge. We also made exploratory between-sex comparisons with our previous report on men. Three groups of women were studied: young exercisers (YE, = 10, 25 ± 1 yr, V̇o: 44 ± 2 mL/kg/min), lifelong aerobic exercisers with a 48 ± 2 yr training history (LLE, = 7, 72 ± 2 yr, V̇o: 26 ± 2 mL/kg/min), and old healthy nonexercisers (OH, = 10, 75 ± 1 yr, V̇o: 18 ± 1 mL/kg/min).

Higher resistance training volume offsets muscle hypertrophy nonresponsiveness in older individuals.

The magnitude of muscle hypertrophy in response to resistance training (RT) is highly variable between individuals (response heterogeneity). Manipulations in RT variables may modulate RT-related response heterogeneity; yet, this remains to be determined. Using a within-subject unilateral design, we aimed to investigate the effects of RT volume manipulation on whole muscle hypertrophy [quadriceps muscle cross-sectional area (qCSA)] among nonresponders and responders to a low RT dose (single-set).

Assessing the impact of boldine on the gastrocnemius using multiomics profiling at 7 and 28 days post-complete spinal cord injury in young male mice.

Spinal cord injury (SCI) results in rapid muscle loss. Exogenous molecular interventions to slow muscle atrophy after SCI have been relatively ineffective and require the search for novel therapeutic targets. Connexin hemichannels (CxHCs) allow nonselective passage of small molecules into and out of the cell.

Dynamic transcriptomic responses to divergent acute exercise stimuli in young adults.

Acute exercise elicits dynamic transcriptional changes that, when repeated, form the fundamental basis of health, resilience, and performance adaptations. While moderate-intensity endurance training combined with conventional resistance training (traditional, TRAD) is often prescribed and recommended by public health guidance, high-intensity training combining maximal-effort intervals with intensive, limited-rest resistance training is a time-efficient alternative that may be used tactically (HITT) to confer similar benefits. Mechanisms of action of these distinct stimuli are incompletely characterized and have not been directly compared.

Muscle fiber type grouping does not change in response to prolonged resistance exercise training in healthy older men.

Background: Ageing of skeletal muscle is characterized in some by muscle fiber type grouping due to denervation-reinnervation cycles, but the severity of fiber type grouping varies widely across individuals of the same chronological age. It remains unknown whether fiber type grouping is associated with lower muscle mass and/or reduced physical function in elderly. Therefore, we assessed the relationship between fiber type grouping and indices of muscle mass and physical function in older adults.

Muscle transcriptomic circuits linked to periarticular physiology in end-stage osteoarthritis.

The ability of individuals with end-stage osteoarthritis (OA) to functionally recover from total joint arthroplasty is highly inconsistent. The molecular mechanisms driving this heterogeneity have yet to be elucidated. Furthermore, OA disproportionately impacts females, suggesting a need for identifying female-specific therapeutic targets.

Considerations for Sex-Cognizant Research in Exercise Biology and Medicine.

As the fields of kinesiology, exercise science, and human movement developed, the majority of the research focused on male physiology and extrapolated findings to females. In the medical sphere, basing practice on data developed in only males resulted in the removal of drugs from the market in the late 1990s due to severe side effects (some life-threatening) in females that were not observed in males. In response to substantial evidence demonstrating exercise-induced health benefits, exercise is often promoted as a key modality in disease prevention, management, and rehabilitation.

State of Knowledge on Molecular Adaptations to Exercise in Humans: Historical Perspectives and Future Directions.

For centuries, regular exercise has been acknowledged as a potent stimulus to promote, maintain, and restore healthy functioning of nearly every physiological system of the human body. With advancing understanding of the complexity of human physiology, continually evolving methodological possibilities, and an increasingly dire public health situation, the study of exercise as a preventative or therapeutic treatment has never been more interdisciplinary, or more impactful. During the early stages of the NIH Common Fund Molecular Transducers of Physical Activity Consortium (MoTrPAC) Initiative, the field is well-positioned to build substantially upon the existing understanding of the mechanisms underlying benefits associated with exercise.

Skeletal muscle properties show collagen organization and immune cell content are associated with resistance exercise response heterogeneity in older persons.

In older individuals, hypertrophy from progressive resistance training (PRT) is compromised in approximately one-third of participants in exercise trials. The objective of this study was to establish novel relationships between baseline muscle features and/or their PRT-induced change in vastus lateralis muscle biopsies with hypertrophy outcomes. Multiple linear regression analyses adjusted for sex were performed on phenotypic data from older adults ( = 48 participants, 70.

Perioperative assessment of muscle inflammation susceptibility in patients with end-stage osteoarthritis.

Many individuals with end-stage osteoarthritis (OA) undergo elective total hip/knee arthroplasty (THA/TKA) to relieve pain, improve mobility and quality of life. However, ∼30% suffer long-term mobility impairment following surgery. This may be in part due to muscle inflammation susceptibility (MuIS+), an overt proinflammatory pathology localized to skeletal muscle surrounding the diseased joint, present in some patients with TKA/THA.

Mechanisms of exercise as a preventative measure to muscle wasting.

Skeletal muscle is the most abundant tissue in healthy individuals and it has important roles in health beyond voluntary movement. The overall mass and energy requirements of skeletal muscle require it to be metabolically active and flexible to multiple energy substrates. The tissue has evolved to be largely load dependent and it readily adapts in a number of positive ways to repetitive overload, such as various forms of exercise training.

Muscle transcriptional networks linked to resistance exercise training hypertrophic response heterogeneity.

The skeletal muscle hypertrophic response to resistance exercise training (RT) is highly variable across individuals. The molecular underpinnings of this heterogeneity are unclear. This study investigated transcriptional networks linked to RT-induced muscle hypertrophy, classified as ) predictive of hypertrophy, ) responsive to RT independent of muscle hypertrophy, or ) plastic with hypertrophy.

Effects of aging and lifelong aerobic exercise on basal and exercise-induced inflammation in women.

Low muscle mass and frailty are especially prevalent in older women and may be accelerated by age-related inflammation. Habitual physical activity throughout the life span (lifelong exercise) may prevent muscle inflammation and associated pathologies, but this is unexplored in women. This investigation assessed basal and acute exercise-induced inflammation in three cohorts of women: young exercisers (YE, = 10, 25 ± 1 yr, [Formula: see text]: 44 ± 2 mL/kg/min, quadriceps size: 59 ± 2 cm), old healthy nonexercisers (OH, = 10, 75 ± 1 yr, [Formula: see text]: 18 ± 1 mL/kg/min, quadriceps size: 40 ± 1 cm), and lifelong aerobic exercisers with a 48 ± 2 yr aerobic training history (LLE, = 7, 72 ± 2 yr, [Formula: see text]: 26 ± 2 mL/kg/min, quadriceps size: 42 ± 2 cm).

Effects of aging and lifelong aerobic exercise on expression of innate immune components in human skeletal muscle.

The purpose of this investigation was to evaluate the effects of aging and lifelong exercise on skeletal muscle components of the innate immune system. Additionally, the effects of an acute resistance exercise (RE) challenge were explored. Three groups of men were studied: young exercisers (YE: = 10, 25 ± 1 yr; V̇o: 53 ± 3 mL/kg/min; quadriceps size: 78 ± 3 cm), lifelong aerobic exercisers with a 53 ± 1 yr training history (LLE; = 21, 74 ± 1 yr; V̇o: 34 ± 1 mL/kg/min; quadriceps size: 67 ± 2 cm), and old healthy nonexercisers (OH: = 10, 75 ± 1 yr; V̇o: 22 ± 1 mL/kg/min, quadriceps size: 56 ± 3 cm).

Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson's Disease.

Parkinson's disease (PD) is the most common motor neurodegenerative disease, and neuromuscular function deficits associated with PD contribute to disability. Targeting these symptoms, our laboratory has previously evaluated 16-week high-intensity resistance exercise as rehabilitative training (RT) in individuals with PD. We reported significant improvements in muscle mass, neuromuscular function (strength, power, and motor unit activation), indices of neuromuscular junction integrity, total and motor scores on the unified Parkinson's disease rating scale (UPDRS), and total and sub-scores on the 39-item PD Quality of Life Questionnaire (PDQ-39), supporting the use of RT to reverse symptoms.

Skeletal muscle transcriptional networks linked to type I myofiber grouping in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder impacting cognition, movement, and quality of life in >10 million individuals worldwide. We recently characterized and quantified a skeletal muscle pathology in PD represented by exaggerated type I myofiber grouping presumed to result from denervation-reinnervation processes. Our previous findings indicated that impaired neuromuscular junction integrity may be involved in type I grouping, which is associated with excessive motor unit activation during weight-bearing tasks.

Effects of aging and lifelong aerobic exercise on basal and exercise-induced inflammation.

Age-associated chronic basal inflammation compromises muscle mass and adaptability, but exercise training may exert an anti-inflammatory effect. This investigation assessed basal and exercise-induced inflammation in three cohorts of men: young exercisers [YE; = 10 men; 25 ± 1 yr; maximal oxygen consumption (V̇o), 53 ± 3 mL·kg·min; quadriceps area, 78 ± 3 cm; means ± SE], old healthy nonexercisers (OH; = 10; 75 ± 1 yr; V̇o, 22 ± 1 mL·kg·min; quadriceps area, 56 ± 3 cm), and lifelong exercisers with an aerobic training history of 53 ± 1 yr (LLE; = 21; 74 ± 1 yr; V̇o, 34 ± 1 mL·kg·min; quadriceps area, 67 ± 2 cm). Resting serum IL-6, TNF-α, C-reactive protein, and IGF-1 levels were measured.

The Importance of Resistance Exercise Training to Combat Neuromuscular Aging.

Older adults undergoing age-related decrements in muscle health can benefit substantially from resistance exercise training, a potent stimulus for whole muscle and myofiber hypertrophy, neuromuscular performance gains, and improved functional mobility. With the use of advancing technologies, research continues to elucidate the mechanisms of and heterogeneity in adaptations to resistance exercise training beyond differences in exercise prescription. This review highlights the current knowledge in these areas and emphasizes knowledge gaps that require future attention of the field.

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 (V̇o) 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.

Myocellular Responses to Concurrent Flywheel Training during 70 Days of Bed Rest.

Purpose: This investigation evaluated myocellular responses to an integrated resistance and aerobic training program during 70 d of bed rest.

Methods: Training was 6 d·wk on a small-footprint gravity-independent flywheel resistance and aerobic device; 3 d of maximal flywheel supine quadriceps and calf exercises with continuous rowing separated by 4 to 6 h, and 3 d of interval rowing. Vastus lateralis (VL) and soleus (SOL) muscle biopsies were obtained from eight healthy males (age, 28 ± 4 yr; BMI, 25 ± 3 kg·m; V˙O2max, 42 ± 6 mL·kg·min) before and after 6° head-down tilt bed rest.

Human neuromuscular aging: Sex differences revealed at the myocellular level.

Age-related muscle loss (sarcopenia) is a major clinical problem affecting both men and women - accompanied by muscle weakness, dysfunction, disability, and impaired quality of life. Current definitions of sarcopenia do not fully encompass the age-related changes in skeletal muscle. We therefore examined the influence of aging and sex on elements of skeletal muscle health using a thorough histopathological analysis of myocellular aging and assessments of neuromuscular performance.

Aspirin as a COX inhibitor and anti-inflammatory drug in human skeletal muscle.

Although aspirin is one of the most common anti-inflammatory drugs in the world, the effect of aspirin on human skeletal muscle inflammation is almost completely unknown. This study examined the potential effects and related time course of an orally consumed aspirin dose on the inflammatory prostaglandin E (PGE)/cyclooxygenase (COX) pathway in human skeletal muscle. Skeletal muscle biopsies were taken from the vastus lateralis of 10 healthy adults (5 male and 5 female, 25 ± 2 yr old) before (Pre) and 2, 4, and 24 h after (Post) a standard dose (975mg) of aspirin and partitioned for analysis of 1) in vivo PGE levels in resting skeletal muscle and 2) ex vivo skeletal muscle PGE production when stimulated with the COX substrate arachidonic acid (5 μM).