Comparison of strategies for assessment of rate of torque development in older and younger adults.

There is increasing appreciation of the role of rate of torque development (RTD) in physical function of older adults (OAs). This study compared various RTD strategies and electromyography (EMG) in the knee extensors and focused on discriminating groups with potential limitations in voluntary activation (VA) and associations of different RTD indices with functional tests that may be affected by VA in OAs. Neuromuscular function was assessed in 20 younger adults (YAs, 22.0 ± 1.7 years) and 50 OAs (74.4 ± 7.0 years). Isometric ballistic and peak torque during maximal voluntary contractions (pkTMVC), doublet stimulation and surface EMG were assessed and used to calculate VA during pkTMVC and RTD and rate of EMG rise during ballistic contractions. Select mobility tests (e.g., gait speed, 5× chair rise) were also assessed in the OAs. Voluntary RTD and RTD normalized to pkTMVC, doublet torque, and peak doublet RTD were compared. Rate of EMG rise and voluntary RTD normalized to pkTMVC did not differ between OAs and YAs, nor were they associated with functional test scores. Voluntary RTD indices normalized to stimulated torque parameters were significantly associated with VA (r = 0.319-0.459), and both indices were significantly lower in OAs vs YAs (all p < 0.020). These RTD indices showed significant association with the majority of mobility tests, but there was no clear advantage among them. Thus, voluntary RTD normalized to pkTMVC was ill-suited for use in OAs, while results suggests that voluntary RTD normalized to stimulated torque parameters may be useful for identifying central mechanisms of RTD impairment in OAs.Clinical trial registration number NCT02505529; date of registration 07/22/2015.

Fsp27 plays a crucial role in muscle performance.

Fsp27 was previously identified as a lipid droplet-associated protein in adipocytes. Various studies have shown that it plays a role in the regulation of lipid homeostasis in adipose tissue and liver. However, its function in muscle, which also accumulate and metabolize fat, remains completely unknown. Our present study identifies a novel role of Fsp27 in muscle performance. Here, we demonstrate that Fsp27-/- and Fsp27+/- mice, both males and females, had severely impaired muscle endurance and exercise capacity compared with wild-type controls. Liver and muscle glycogen stores were similar among all groups fed or fasted, and before or after exercise. Reduced muscle performance in Fsp27-/- and Fsp27+/- mice was associated with severely decreased fat content in the muscle. Furthermore, results in heterozygous Fsp27+/- mice indicate that Fsp27 haploinsufficiency undermines muscle performance in both males and females. In summary, our physiological findings reveal that Fsp27 plays a critical role in muscular fat storage, muscle endurance, and muscle strength.NEW & NOTEWORTHY This is the first study identifying Fsp27 as a novel protein associated with muscle metabolism. The Fsp27-knockout model shows that Fsp27 plays a role in muscular-fat storage, muscle endurance, and muscle strength, which ultimately impacts limb movement. In addition, our study suggests a potential metabolic paradox in which FSP27-knockout mice presumed to be metabolically healthy based on glucose utilization and oxidative metabolism are unhealthy in terms of exercise capacity and muscular performance.

Discrepancies in hand motor performance and executive function in older adults.

There is increasing interest in using motor function tests to identify risk of cognitive impairment in older adults (OA). This study examined associations among grip strength, with and without adjustment for muscle mass, manual dexterity and Trail Making Test (TMT) A and B in 77 OA (73.4 ± 5.2 years) with globally intact cognition. A subset of OA who exhibited mismatched motor function (e.g., in the highest strength and lowest dexterity tertiles, or vice versa) was identified and analyzed. Dexterity showed stronger associations with TMT-A and -B than grip strength (absolute or adjusted). OA with mismatched motor function scored worse on tests of TMT-B, but not -A than those with matched motor function. Dexterity may have more promise than grip strength for identifying increased risk of cognitive impairment. Intriguing, though limited, data suggest that mismatched motor function (strength vs. dexterity) in OAs might be an even more robust marker of such risk.

Dietary fish oil supplement induces age-specific contractile and proteomic responses in muscles of male rats.

BACKGROUND: Dietary fish oil (DFO) has been identified as a micronutrient supplement with the potential to improve musculoskeletal health in old age. Few data are available for effects of DFO on muscle contractility, despite the significant negative impact of muscle weakness on age-related health outcomes. Accordingly, the effects of a DFO intervention on the contractile function and proteomic profile of adult and aged in an animal model of aging were investigated. METHODS: This preliminary study evaluated 14 adult (8 months) and 12 aged (22 months) male, Sprague-Dawley rats consuming a DFO-supplemented diet or a control diet for 8 weeks (7 adult and 6 aged/dietary group). Animal weight, food intake and grip strength were assessed at the start and end of the FO intervention. In situ force and contractile properties were measured in the medial gastrocnemius muscle following the intervention and muscles were processed for 2-D gel electrophoresis and proteomic analysis via liquid chromatography with tandem mass spectrometry, confirmed by immunoblotting. Effects of age, diet and age x diet interaction were evaluated by 2-way ANOVA. RESULTS: A significant (P = 0.022) main effect for DFO to increase (~ 15%) muscle contractile force was observed, without changes in muscle mass. Proteomic analysis revealed a small number of proteins that differed across age and dietary groups at least 2-fold, most of which related to metabolism and oxidative stress. In seven of these proteins (creatine kinase, triosephosphate isomerase, pyruvate kinase, parvalbumin, beta-enolase, NADH dehydrogenase and Parkin7/DJ1), immunoblotting corroborated these findings. Parvalbumin showed only an effect of diet (increased with DFO) (P = 0.003). Significant age x diet interactions were observed in the other proteins, generally demonstrating increased expression in adult and decreased expression aged rats consuming DFO (all P > 0.011). However, correlational analyses revealed no significant associations between contractile parameters and protein abundances. CONCLUSIONS: Results of this preliminary study support the hypothesis that DFO can enhance musculoskeletal health in adult and aged muscles, given the observed improvement in contractile function. The fish oil supplement also alters protein expression in an age-specific manner, but the relationship between proteomic and contractile responses remains unclear. Further investigation to better understand the magnitude and mechanisms muscular effects of DFO in aged populations is warranted.

Relative contribution of muscle strength, lean mass, and lower extremity motor function in explaining between-person variance in mobility in older adults.

BACKGROUND: Approximately 35% of individuals > 70 years have mobility limitations. Historically, it was posited lean mass and muscle strength were major contributors to mobility limitations, but recent findings indicate lean mass and muscle strength only moderately explain mobility limitations. One likely reason is that lean mass and muscle strength do not necessarily incorporate measures globally reflective of motor function (defined as the ability to learn, or to demonstrate, the skillful and efficient assumption, maintenance, modification, and control of voluntary postures and movement patterns). In this study we determined the relative contribution of lean mass, muscle strength, and the four square step test, as an index of lower extremity motor function, in explaining between-participant variance in mobility tasks. METHODS: In community-dwelling older adults (N = 89; 67% women; mean 74.9 ± 6.7 years), we quantified grip and leg extension strength, total and regional lean mass, and time to complete the four square step test. Mobility was assessed via 6-min walk gait speed, stair climb power, 5x-chair rise time, and time to complete a complex functional task. Multifactorial linear regression modeling was used to determine the relative contribution (via semi-partial r2) for indices of lean mass, indices of muscle strength, and the four square step test. RESULTS: When aggregated by sex, the four square step test explained 17-34% of the variance for all mobility tasks (p <  0.01). Muscle strength explained ~ 12% and ~ 7% of the variance in 6-min walk gait speed and 5x-chair rise time, respectively (p <  0.02). Lean mass explained 32% and ~ 4% of the variance in stair climb power and complex functional task time, respectively (p <  0.02). When disaggregated by sex, lean mass was a stronger predictor of mobility in men. CONCLUSION: The four square step test is uniquely associated with multiple measures of mobility in older adults, suggesting lower extremity motor function is an important factor for mobility performance. TRIAL REGISTRATION: NCT02505529 -2015/07/22.

Muscle-specificity of age-related changes in markers of autophagy and sphingolipid metabolism.

Our previous findings indicate that the gastrocnemius muscle of aging rats exhibits impairments of muscle quality (force/unit muscle tissue) and autophagy and increased sarcoplasmic reticulum stress. The purpose of this study was to examine age-related changes in soleus muscle contractility and in markers of autophagy in the soleus and gastrocnemius muscles. We assessed in situ muscle force and size in the soleus muscle of adult (7-8 months) and aged (24-26 months) male, F344/BN rats. We used immunoblotting to compare abundance of markers of autophagy, sarcoplasmic reticulum (SR) stress and sphingolipid metabolism in the soleus and medial gastrocnemius (MG) muscles of these animals. Relative to adults, aged rats maintained soleus muscle quality and increased muscle size, resulting in increased tetanic force production. Immunoblotting revealed a general pattern of an age-related reduction of basal autophagy, despite increases in indicators of SR stress and upstream autophagic pathway activation in the MG. The MG also exhibited changes in markers of sphingolipid metabolism suggestive of increased muscle ceramide. Minimal age-related changes were observed in the soleus. The soleus maintains muscle mass and quality with age, and exhibits fewer age-related changes in markers of stress and autophagy than the MG. Based on these data, we suggest that maintenance of autophagy may preserve muscle quality by preventing excessive SR stress.

Fracture discrimination capability of ulnar flexural rigidity measured via Cortical Bone Mechanics Technology: study protocol for The STRONGER Study.

Osteoporosis is characterized by low bone mass and structural deterioration of bone tissue, which leads to bone fragility (ie, weakness) and an increased risk for fracture. The current standard for assessing bone health and diagnosing osteoporosis is DXA, which quantifies areal BMD, typically at the hip and spine. However, DXA-derived BMD assesses only one component of bone health and is notably limited in evaluating the bone strength, a critical factor in fracture resistance. Although multifrequency vibration analysis can quickly and painlessly assay bone strength, there has been limited success in advancing a device of this nature. Recent progress has resulted in the development of Cortical Bone Mechanics Technology (CBMT), which conducts a dynamic 3-point bending test to assess the flexural rigidity (EI) of ulnar cortical bone. Data indicate that ulnar EI accurately estimates ulnar whole bone strength and provides unique and independent information about cortical bone compared to DXA-derived BMD. Consequently, CBMT has the potential to address a critical unmet need: Better identification of patients with diminished bone strength who are at high risk of experiencing a fragility fracture. However, the clinical utility of CBMT-derived EI has not yet been demonstrated. We have designed a clinical study to assess the accuracy of CBMT-derived ulnar EI in discriminating post-menopausal women who have suffered a fragility fracture from those who have not. These data will be compared to DXA-derived peripheral and central measures of BMD obtained from the same subjects. In this article, we describe the study protocol for this multi-center fracture discrimination study (The STRONGER Study).

Acute effects of sex-specific sex hormones on heat shock proteins in fast muscle of male and female rats.

Heat shock protein (HSP) expression and sex hormone levels have been shown to influence several aspects of skeletal muscle physiology (e.g., hypertrophy, resistance to oxidative stress), suggesting that sex hormone levels can effect HSP expression. This study evaluated the effects of differing levels of sex-specific sex hormones (i.e., testosterone in males and estrogen in females) on the expression of 4: HSP70, HSC70, HSP25, and αB-crystallin in the quadriceps muscles of male and female rats. Animals were assigned to 1 of 3 groups (n = 5 M and F/group). The first group (Ctl) consisted of typically cage-housed animals that served as controls. The second group (H) was gonadectomized and received either testosterone (males) or estradiol (females) via injection for 12 consecutive days. The third group (Gx) was gonadectomized and injected as above, but with vehicle only, rather than hormones. Significant sex by condition interactions (P < 0.05 by two-way MANOVA) were found for all 4 proteins studied, except for HSP70, which exhibited a significant effect of condition only. The expression of all HSPs was greater (1.9-2.5-fold) in males vs. females in the Ctl group, except for HSP70, which was no different. Generally, gonadectomy appeared to have greater effects in males than females, but administration of the exogenous sex hormones tended to produce more robust relative changes in females than males. There were no differences in myosin composition in any of the groups, suggesting that changes in fiber type were not a factor in the differential protein expression. These data may have implications for sex-related differences in muscular responses to exercise, disuse, and injury.

Genetic deletion of Kvß2 (AKR6) causes loss of muscle function and increased inflammation in mice.

The voltage-gated potassium channels (Kv) are complex ion channels with distinct roles in neurotransmission, electrical conductivity of the heart, and smooth and striated muscle functions. Previously, we demonstrated that deletion of Kvß2 in mice results in decreased Pax7 protein levels, hindlimb muscles and body weights, and fiber type switching. In the present study, we tested the hypothesis that Kvß2 regulates skeletal muscle function in mice. The young and old Kvß2 knockout (KO) and wildtype (WT) mice were utilized to test the aging phenotype and skeletal muscle function. Consistent with our previous finding, we found a significant reduction in hindlimb skeletal muscles mass and body weight in young Kvß2 KO mice, which was also significantly reduced in old Kvß2 KO mice compared with age-matched WT mice. Forelimb grip strength, and the hindleg extensor digitorum longus (EDL) muscles force-frequency relations were significantly decreased in young and old Kvß2 KO mice compared to age-matched WT mice. Analysis of transmission electron microscopy images of EDL muscles in young mice revealed a significant reduction in the sarcomere length for Kvß2 KO vs. WT. Hematoxylin and eosin-stained tibialis anterior muscles cryosections displayed a significant decrease in the number of medium (2,000-4,000 µm2) and largest (>4,000 µm2) myofibers area in young Kvß2 KO vs. WT mice. We also found a significant increase in fibrotic tissue area in young Kvß2 KO mice compared with age-matched WT mice. Analysis of RNA Seq data of the gastrocnemius muscles (GAS) identified significant increase in genes involved in skeletal muscle development, proliferation and cell fate determination, atrophy, energy metabolism, muscle plasticity, inflammation, and a decrease in circadian core clock genes in young Kvß2 KO vs. WT mice. Several genes were significantly upregulated (384 genes) and downregulated (40 genes) in young Kvß2 KO mice compared to age-matched WT mice. Further, RT-qPCR analysis of the GAS muscles displayed a significant increase in pro-inflammatory marker Il6 expression in young Kvß2 KO mice compared to age-matched WT mice. Overall, the present study shows that deletion of Kvß2 leads to decreased muscles strength and increased inflammation.

"SR stress" in mixed hindlimb muscles of aging male rats.

Impaired sarcoplasmic reticulum (SR) function has been associated with reduced muscle force generation and locomotor function in aging animals. This study was conducted to determine the extent to which aging increased SR stress markers in male rats, and the extent to which volitional exercise affected them. We harvested medial gastrocnemius muscles from F344/BN rats that were adult (8 months; n = 8), aging (24 months; n = 8) and that aged with wheel access for 16 months (24 months; n = 4). SR calcium handling assays and immunoblotting (Caspase 12, dysferlin and LC3) were performed on crude homogenates and SR-enriched microsomal fractions. Aging was associated with increased Caspase 12 and SR dysferlin, as well as a reduced LC3II/I ratio and impaired calcium release. Despite further increases in Caspase 12, voluntary wheel running partially restored SR calcium release and dysferlin toward younger levels. Of note, the LC3II/I was also partially restored in the voluntary wheel running group, suggesting increased autophagy. These results suggest that impaired SR function with aging is associated with age-related increases in SR stress, possibly related to reduced autophagy. Long-term volitional exercise improved SR function and markers of autophagy, despite increased Caspase 12, suggesting that running contributed a beneficial stress that differed from the "distress" of sedentary aging.

A preliminary study of symptomatic fatigue in rural older adults.

BACKGROUND AND AIMS: The purpose of this study was to evaluate the prevalence of symptomatic fatigue and its relation to physical function and self-perceived health in a sample of older, rural community-dwelling adults with commonly-used clinical fatigue scales. METHODS: This is an exploratory, descriptive study of 30 subjects from 4 rural counties. All subjects were 70+ years of age and had no recent history of hospitalization. Subjects were assessed in their homes and completed a standard test of physical function, twelve functional assessment instruments, and two commonly-used clinical fatigue scales: the Fatigue Severity Scale and the Functional Assessment of Chronic Illness Therapy-Fatigue Scale. RESULTS: Depending on the fatigue instrument and criteria used, 23-47% of subjects exhibited symptomatic fatigue. Regardless of the scale, fatigue was associated with several negative consequences: decreased physical function performance, lower morale, and reduced physical composite scores on the Short Form-36 quality of life questionnaire. Of note, these differences remained significant even after accounting for depression scale scores. In addition, fatigue was associated with a greater incidence of risk for malnutrition. CONCLUSIONS: Together, these findings suggest that symptomatic fatigue may be quite prevalent in older individuals in rural settings, and warrants further consideration when presented in the clinical setting, as it may be associated with several negative health outcomes.

Nampt activator P7C3 ameliorates diabetes and improves skeletal muscle function modulating cell metabolism and lipid mediators.

BACKGROUND: Nicotinamide phosphoribosyltransferase (Nampt), a key enzyme in NAD salvage pathway is decreased in metabolic diseases, and its precise role in skeletal muscle function is not known. We tested the hypothesis, Nampt activation by P7C3 (3,6-dibromo-α-[(phenylamino)methyl]-9H-carbazol-9-ethanol) ameliorates diabetes and muscle function. METHODS: We assessed the functional, morphometric, biochemical, and molecular effects of P7C3 treatment in skeletal muscle of type 2 diabetic (db/db) mice. Nampt+/- mice were utilized to test the specificity of P7C3. RESULTS: Insulin resistance increased 1.6-fold in diabetic mice compared with wild-type mice and after 4 weeks treatment with P7C3 rescued diabetes (P < 0.05). In the db-P7C3 mice fasting blood glucose levels decreased to 0.96-fold compared with C57Bl/6J wild-type naïve control mice. The insulin and glucose tolerance tests blood glucose levels were decreased to 0.6-fold and 0.54-folds, respectively, at 120 min along with an increase in insulin secretion (1.76-fold) and pancreatic ß-cells (3.92-fold) in db-P7C3 mice. The fore-limb and hind-limb grip strengths were increased to 1.13-fold and 1.17-fold, respectively, together with a 14.2-fold increase in voluntary running wheel distance in db-P7C3 mice. P7C3 treatment resulted in a 1.4-fold and 7.1-fold increase in medium-sized and larger-sized myofibres cross-sectional area, with a concomitant 0.5-fold decrease in smaller-sized myofibres of tibialis anterior (TA) muscle. The transmission electron microscopy images also displayed a 1.67-fold increase in myofibre diameter of extensor digitorum longus muscle along with 2.9-fold decrease in mitochondrial area in db-P7C3 mice compared with db-Veh mice. The number of SDH positive myofibres were increased to 1.74-fold in db-P7C3 TA muscles. The gastrocnemius and TA muscles displayed a decrease in slow oxidative myosin heavy chain type1 (MyHC1) myofibres expression (0.46-fold) and immunostaining (6.4-fold), respectively. qPCR analysis displayed a 2.9-fold and 1.3-fold increase in Pdk4 and Cpt1, and 0.55-fold and 0.59-fold decrease in Fgf21 and 16S in db-P7C3 mice. There was also a 3.3-fold and 1.9-fold increase in Fabp1 and CD36 in db-Veh mice. RNA-seq differential gene expression volcano plot displayed 1415 genes to be up-regulated and 1726 genes down-regulated (P < 0.05) in db-P7C3 mice. There was 1.02-fold increase in serum HDL, and 0.9-fold decrease in low-density lipoprotein/very low-density lipoprotein ratio in db-P7C3 mice. Lipid profiling of gastrocnemius muscle displayed a decrease in inflammatory lipid mediators n-6; AA (0.83-fold), and n-3; DHA (0.69-fold) and EPA (0.81-fold), and a 0.66-fold decrease in endocannabinoid 2-AG and 2.0-fold increase in AEA in db-P7C3 mice. CONCLUSIONS: Overall, we demonstrate that P7C3 activates Nampt, improves type 2 diabetes and skeletal muscle function in db/db mice.

Effects of early-stage aging on locomotor dynamics and hindlimb muscle force production in the rat.

Attenuation of locomotor function is common in many species of animals as they age. Dysfunctions may emerge from a constellation of age-related impairments, including increased joint stiffness, reduced ability to repair muscle tissue, and decreasing fine motor control capabilities. Any or all of these factors may contribute to gait abnormalities and substantially limit an animal's speed and mobility. In this study we examined the effects of aging on whole-animal locomotor performance and hindlimb muscle mechanics in young adult rats aged 6-8 months and 'early aged' 24-month-old rats (Rattus norvegicus, Fischer 344 × Brown Norway crosses). Analyses of gaits and kinematics demonstrated that aged rats moved significantly more slowly, sustained longer hindlimb support durations, moved with a greater proportion of asymmetrical gaits, were more plantigrade, and moved with a more kyphotic spinal posture than the young rats. Additionally, the external mechanical energy profiles of the aged animals were variable across trials, whereas the younger rats moved predominantly with bouncing mechanics. In situ analyses of the ankle extensor/plantar flexor muscle group (soleus, plantaris, and medial and lateral gastrocnemii) revealed reduced maximum force generation with aging, despite minimal changes in muscle mass. The weakened muscles were implicated in the degradation of hindfoot posture, as well as variability in center-of-mass mechanics. These results demonstrate that the early stages of aging have consequences for whole-body performance, even before age-related loss of muscle mass begins.

Multiple measures of muscle function influence Sorensen Test performance in individuals with recurrent low back pain.

BACKGROUND: Sorensen Test time-to-task-failure (TTF) predicts several low back pain (LBP) clinical outcomes, including recurrence. Because the test is described as a measure of trunk extensor (TE) muscle endurance, LBP rehabilitation programs often emphasize endurance training, but the direct role of TE muscle function on Sorensen Test-TTF remains unclear. OBJECTIVE: To assess the discriminative and associative properties of multiple markers of isolated TE performance with regard to Sorensen Test-TTF in individuals with recurrent LBP. METHOD: Secondary analysis of baseline measures from participants in a registered (NCT02308189) trial (10 men; 20 women) was performed. Participants were classified by Sorensen Test-TTF as high, moderate or low risk for subsequent LBP episodes, and compared to determine if classification could discriminate differences in TE function. Correlations between Sorensen Test-TTF and isolated TE performance, anthropometrics and disability were investigated. RESULTS: Individuals at risk of subsequent LBP episodes had greater perceived disability and fat mass/TE strength ratios (P⩽ 0.05) than those not at risk. Modest, significant (r= 0.36-0.42, P⩽ 0.05) associations were found between Sorensen Test-TTF, TE endurance and fat mass/TE strength. Exploratory analyses suggested possible sex-specific differences related to Sorensen Test-TTF. CONCLUSIONS: Isolated TE muscle endurance is only one of several factors with similar influence on Sorensen Test-TFF, thus LBP rehabilitation strategies should consider other factors, including TE strength, anthropometrics and perceived disability.

Reduced Neural Excitability and Activation Contribute to Clinically Meaningful Weakness in Older Adults.

BACKGROUND: Weakness is a risk factor for physical limitations and death in older adults (OAs). We sought to determine whether OAs with clinically meaningful leg extensor weakness exhibit differences in voluntary inactivation (VIA) and measures of corticospinal excitability when compared to young adults (YAs) and OAs without clinically meaningful weakness. We also sought to estimate the relative contribution of indices of neural excitability and thigh lean mass in explaining the between-subject variability in OAs leg extensor strength. METHODS: In 66 OAs (75.1 ± 7.0 years) and 20 YAs (22.0 ± 1.9 years), we quantified leg extensor strength, thigh lean mass, VIA, and motor evoked potential (MEP) amplitude and silent period (SP) duration. OAs were classified into weakness groups based on previously established strength/body weight (BW) cut points (Weak, Modestly Weak, or Not Weak). RESULTS: The OAs had 63% less strength/BW when compared to YAs. Weak OAs exhibited higher levels of leg extensor VIA than Not Weak OAs (14.2 ± 7.5% vs 6.1 ± 7.5%). Weak OAs exhibited 24% longer SPs compared to Not Weak OAs, although this difference was insignificant (p = .06). The Weak OAs MEPs were half the amplitude of the Not Weak OAs. Regression analysis indicated that MEP amplitude, SP duration, and thigh lean mass explained ~62% of the variance in strength, with the neural excitability variables explaining ~33% of the variance and thigh lean mass explaining ~29%. CONCLUSION: These findings suggest that neurotherapeutic interventions targeting excitability could be a viable approach to increase muscle strength in order to reduce the risk of physical impairments in late life.

Heterogeneity of the strength response to progressive resistance exercise training in older adults: Contributions of muscle contractility.

BACKGROUND: Older adults display wide individual variability (heterogeneity) in the effects of resistance exercise training on muscle strength. The mechanisms driving this heterogeneity are poorly understood. Understanding of these mechanisms could permit development of more targeted interventions and/or improved identification of individuals likely to respond to resistance training interventions. Thus, this study assessed potential physiological factors that may contribute to strength response heterogeneity in older adults: neural activation, muscle hypertrophy, and muscle contractility. METHODS: In 24 older adults (72.3 ± 6.8 years), we measured the following parameters before and after 12 weeks of progressive resistance exercise training: i) isometric leg extensor strength; ii) isokinetic (60°/sec) leg extensor strength; iii) voluntary (neural) activation by comparing voluntary and electrically-stimulated muscle forces (i.e., superimposed doublet technique); iv) muscle hypertrophy via dual-energy x-ray absorptiometry (DXA) estimates of regional lean tissue mass; and v) intrinsic contractility by electrically-elicited twitch and doublet torques. We examined associations between physiological factors (baseline values and relative change) and the relative change in isometric and isokinetic muscle strength. RESULTS: Notably, changes in quadriceps contractility were positively associated with the relative improvement in isokinetic (r = 0.37-0.46, p ≤ 0.05), but not isometric strength (r = 0.09-0.21). Change in voluntary activation did not exhibit a significant association with the relative improvements in either isometric or isokinetic strength (r = 0.35 and 0.33, respectively; p > 0.05). Additionally, change in thigh lean mass was not significantly associated with relative improvement in isometric or isokinetic strength (r = 0.09 and -0.02, respectively; p > 0.05). Somewhat surprising was the lack of association between exercise-induced changes in isometric and isokinetic strength (r = 0.07). CONCLUSIONS: The strength response to resistance exercise in older adults appears to be contraction-type dependent. Therefore, future investigations should consider obtaining multiple measures of muscle strength to ensure that strength adaptations are comprehensively assessed. Changes in lean mass did not explain the heterogeneity in strength response for either contraction type, and the data regarding the influence of voluntary activation was inconclusive. For isokinetic contraction, the strength response was moderately explained by between-subject variance in the resistance-exercise induced changes in muscle contractility.

Distinguishing chronic low back pain in young adults with mild to moderate pain and disability using trunk compliance.

Chronic low back pain (cLBP) rates among younger individuals are rising. Although pain and disability are often less severe, underlying changes in trunk behavior may be responsible for recurrence. We examine the biomarker capacity of a simple Trunk Compliance Index (TCI) to distinguish individuals with and without cLBP. A random subset (n = 49) of the RELIEF RCT were matched to healthy controls for sex, age, height and weight. We measured TCI (as displacement/ weight-normalized perturbation force) using anthropometrically-matched, suddenly-applied pulling perturbations to the trunk segment, randomized across three planes of motion (antero-posterior, medio-lateral, and rotational). Mean differences between cLBP, sex and perturbation direction were assessed with repeated-measures analysis of variance. Discriminatory accuracy of TCI was assessed using Receiver Operator Characteristic (ROC) analysis. Baseline characteristics between groups were equivalent (x̅ [range]): sex (57% female / group), age (23.0 [18-45], 22.8 [18-45]), height, cm (173.0 [156.5-205], 171.3 [121.2-197], weight, kg (71.8 [44.5-116.6], 71.7 [46.8-117.5]) with cLBP associated with significantly lower TCI for 5 of 6 directions (range mean difference, - 5.35: - 1.49, range 95% CI [- 6.46: - 2.18 to - 4.35: - 0.30]. Classification via ROC showed that composite TCI had high discriminatory potential (area under curve [95% CI], 0.90 [0.84-0.96]), driven by TCI from antero-posterior perturbations (area under curve [95% CI], 0.99 [0.97-1.00]). Consistent reductions in TCI suggests global changes in trunk mechanics that may go undetected in classic clinical examination. Evaluation of TCI in younger adults with mild pain and disability may serve as a biomarker for chronicity, leading to improved preventative measures in cLBP.Trial Registration and Funding RELIEF is registered with clinicaltrials.gov (NCT01854892) and funded by the NIH National Center for Complementary & Integrative Health (R01AT006978).

Is impaired dopaminergic function associated with mobility capacity in older adults?

The capacity to move is essential for independence and declines with age. Slow movement speed, in particular, is strongly associated with negative health outcomes. Prior research on mobility (herein defined as movement slowness) and aging has largely focused on musculoskeletal mechanisms and processes. More recent work has provided growing evidence for a significant role of the nervous system in contributing to reduced mobility in older adults. In this article, we report four pieces of complementary evidence from behavioral, genetic, and neuroimaging experiments that, we believe, provide theoretical support for the assertion that the basal ganglia and its dopaminergic function are responsible, in part, for age-related reductions in mobility. We report four a posteriori findings from an existing dataset: (1) slower central activation of ballistic force development is associated with worse mobility among older adults; (2) older adults with the Val/Met intermediate catecholamine-O-methyl-transferase (COMT) genotype involved in dopamine degradation exhibit greater mobility than their homozygous counterparts; (3) there are moderate relationships between performance times from a series of lower and upper extremity tasks supporting the notion that movement speed in older adults is a trait-like attribute; and (4) there is a relationship of functional connectivity within the medial orbofrontal (mOFC) cortico-striatal network and measures of mobility, suggesting that a potential neural mechanism for impaired mobility with aging is the deterioration of the integrity of key regions within the mOFC cortico-striatal network. These findings align with recent basic and clinical science work suggesting that the basal ganglia and its dopaminergic function are mechanistically linked to age-related reductions in mobility capacity.

Men and women exhibit a similar time to task failure for a sustained, submaximal elbow extensor contraction.

Sex differences in muscle fatigue-resistance have been observed in a variety of muscles and under several conditions. This study compared the time to task failure (TTF) of a sustained isometric elbow extensor (intensity 15% of maximal strength) contraction in young men (n = 12) and women (n = 11), and examined if their neurophysiologic adjustments to fatigue differed. Motor-evoked potential amplitude (MEP), silent period duration, interference electromyogram (EMG) amplitude, maximal muscle action potential (M (max)), heart rate, and mean arterial pressure were measured at baseline, during the task, and during a 2-min ischemia period. Men and women did not differ in TTF (478.2 +/- 31.9 vs. 500.4 +/- 41.3 s; P = 0.67). We also performed an exploratory post hoc cluster analysis, and classified subjects as low (n = 15) or high endurance (n = 8) based on TTF (415.3 +/- 16.0 vs. 626.7 +/- 25.8 s, respectively). The high-endurance group exhibited a lower MEP and EMG at baseline (MEP 16.3 +/- 4.1 vs. 37.2 +/- 3.0% M (max), P < 0.01; EMG 0.98 +/- 0.18 vs. 1.85 +/- 0.26% M (max), P = 0.03). These findings suggest no sex differences in elbow extensor fatigability, in contrast to observations from other muscle groups. The cluster analyses results indicated that high- and low-endurance groups displayed neurophysiologic differences at baseline (before performing the fatigue task), but that they did not differ in fatigue-induced changes in their neurophysiologic adjustments to the task.

Perspective: Pragmatic Exercise Recommendations for Older Adults: The Case for Emphasizing Resistance Training.

Optimal health benefits from exercise are achieved by meeting both aerobic and muscle strengthening guidelines, however, most older adults (OAs) do not exercise and the majority of those who do only perform one type of exercise. A pragmatic solution to this problem may be emphasizing a single exercise strategy that maximizes health benefits. The loss of muscle mass and strength at an accelerated rate are hallmarks of aging that, without intervention, eventually lead to physical disability and loss of independence. Additionally, OAs are at risk of developing several chronic diseases. As such, participating in activities that can maintain or increase muscle mass and strength, as well as decrease chronic disease risk, is essential for healthy aging. Unfortunately, there is a widely held belief that adaptations to aerobic and resistance exercise are independent of each other, requiring the participation of both types of exercise to achieve optimal health. However, we argue that this assertion is incorrect, and we discuss crossover adaptations of both aerobic and resistance exercise. Aerobic exercise can increase muscle mass and strength, though not consistently and may be limited to exercise that overloads a particular muscle group, such as stationary bicycling. In contrast, resistance exercise is effective at maintaining muscle health with increasing age, and also has significant effects on cardiovascular disease (CVD) risk factors, type 2 diabetes (T2D), cancer, and mortality. We posit that resistance exercise is the most effective standalone exercise strategy for improving overall health in OAs and should be emphasized in future guidelines.