Managing Refractory Hypertension: A Case Study Exploring the Influence of ACE and ACTN3 Gene Polymorphisms

Pickering, C, Suraci, B, Semenova, EA, Boulygina, EA, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Leońska-Duniec, A, Pająk, B, Chycki, J, Moska, W, Lulińska-Kuklik, E, Dornowski, M, Maszczyk, A, Bradley, B, Kana-ah, A, Cięszczyk, P, Generozov, EV, and Ahmetov, II. A genome-wide association study of sprint performance in elite youth football players. J Strength Cond Res 33(9): 2344-2351, 2019-Sprint speed is an important component of football performance, with teams often placing a high value on sprint and acceleration ability. The aim of this study was to undertake the first genome-wide association study to identify genetic variants associated with sprint test performance in elite youth football players and to further validate the obtained results in additional studies. Using micro-array data (600 K-1.14 M single nucleotide polymorphisms [SNPs]) of 1,206 subjects, we identified 12 SNPs with suggestive significance after passing replication criteria. The polymorphism rs55743914 located in the PTPRK gene was found as the most significant for 5-m sprint test (p = 7.7 × 10). Seven of the discovered SNPs were also associated with sprint test performance in a cohort of 126 Polish women, and 4 were associated with power athlete status in a cohort of 399 elite Russian athletes. Six SNPs were associated with muscle fiber type in a cohort of 96 Russian subjects. We also examined genotype distributions and possible associations for 16 SNPs previously linked with sprint performance. Four SNPs (AGT rs699, HSD17B14 rs7247312, IGF2 rs680, and IL6 rs1800795) were associated with sprint test performance in this cohort. In addition, the G alleles of 2 SNPs in ADRB2 (rs1042713 & rs1042714) were significantly over-represented in these players compared with British and European controls. These results suggest that there is a genetic influence on sprint test performance in footballers, and identifies some of the genetic variants that help explain this influence.

The aim of the study was to evaluate the possibility to predict the muscle fiber-type proportion in men of different sports specialization by testing the maximal torque production by knee extensors at different velocities. For this reason the proportion of fast- and slow-twitch muscle fibers (MFs) in m. vastus lateralis of 23 athletes (11 endurance and 12 power athletes), as well the maximal torque production of knee extensors at various angular velocities in isokinetic mode were determined. The group of strength trained athletes significantly exceeded the group of endurance trained athletes in body mass, body mass index, volume of the m. quadriceps femoris, maximum torque production, and specific force at angular velocities 30, 180 and 300 degrees per second. In contrast to cross-sectional area (CSA) of slow-twitch MFs, the average CSA of fast-twitch MFs and the proportion of fast-twitch MFs in the group of power athletes significantly exceeded those in the group of endurance athletes. In the combined group of volunteers (n = 23), the proportion of fast-twitch MFs significantly correlated with the torque production at high angular velocities (r = 0.51 and p = 0.01 at 180 deg/s; r = 0.47 and p = 0.02 at 300 deg/s). We did not find any correlation between these parameters in the separate groups of power and endurance athletes. The results indicate a low accuracy in predicting the proportion of fast-twitch MF in m. vastus lateralis in athletes using the maximal torque production of knee extensors at different angular velocities. Significant correlation between the proportion of fast-twitch MF and maximal torque at high angular velocities in the general group (n = 23) was due to the presence of two significantly different subgroups.

Guilherme, JPLF, Semenova, EA, Borisov, OV, Kostryukova, ES, Vepkhvadze, TF, Lysenko, EA, Andryushchenko, ON, Andryushchenko, LB, Lednev, EM, Larin, AK, Bondareva, EA, Generozov, EV, and Ahmetov, II. The BDNF-increasing allele is associated with increased proportion of fast-twitch muscle fibers, handgrip strength, and power athlete status. J Strength Cond Res 36(7): 1884-1889, 2022-The brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and formation of regenerated myofibers following injury or damage. A recent study suggested that the BDNF overexpression increases the proportion of fast-twitch muscle fibers, while the BDNF deletion promotes a fast-to-slow transition. The purpose of this study was to evaluate the association between the BDNF gene rs10501089 polymorphism (associated with blood BDNF levels), muscle fiber composition, and power athlete status. Muscle fiber composition was determined in 164 physically active individuals (113 men, 51 women). BDNF genotype and allele frequencies were compared between 508 Russian power athletes, 178 endurance athletes, and 190 controls. We found that carriers of the minor A-allele (the BDNF-increasing allele) had significantly higher percentage of fast-twitch muscle fibers than individuals homozygous for the G-allele (males: 64.3 [7.8] vs. 50.3 [15.8]%, p = 0.0015; all subjects: 64.1 ± 7.9 vs. 49.6 ± 14.7%, p = 0.0002). Furthermore, the A-allele was associated (p = 0.036) with greater handgrip strength in a sub-group of physically active subjects (n = 83) and over-represented in power athletes compared with controls (7.7 vs. 2.4%, p = 0.0001). The presence of the A-allele (i.e., AA+AG genotypes) rather than GG genotype increased the odds ratio of being a power athlete compared with controls (odds ratio [OR]: 3.43, p = 0.00071) or endurance athletes (OR: 2.36, p = 0.0081). In conclusion, the rs10501089 A-allele is associated with increased proportion of fast-twitch muscle fibers and greater handgrip strength, and these may explain, in part, the association between the AA/AG genotypes and power athlete status.

This investigation aimed to explore the effects of ACE I/D and ACTN3 R577X gene polymorphisms on specific quantitative variables, including height, weight, arm span, biacromial breadth, forced vital capacity (FVC), FVC/weight, maximal oxygen uptake (VO2max), prone bench pull (PBP), loaded barbell squat (LBS), and 3,000-m run, in 243 Chinese rowing athletes. The ACE and ACTN3 genotypes were obtained for each athlete via polymerase chain reaction on saliva samples, and the genotype frequency was analyzed. The ACE genotype frequency of rowing athletes were 45.8% II, 42.2% ID, and 12% DD for males and 33.6% II, 48% ID, and 18.4% DD for females. There were significant differences in weight in male athletes, PBP in female athletes, and ACE genotypes. A linear regression analysis using PBP and LBS as different dependent variables and ACE genotypes as independent variables based on the ACE I allele additive genetic effect showed a statistical significance in female athletes (p < 0.05). There was a significant difference in the distribution of the three genotypes among male athletes (36.7% XX, 38.5% RX, and 24.8% RR, χ2 = 5.191, df = 2, p = 0.022 < 0.05). There were no significant differences in the distribution of the three genotypes among female athletes (23.8% XX, 47.8% RX, 28.4% RR, χ 2 = 0.24, df = 2, p = 0.619 > 0.05). The ACTN3 gene polymorphism of male rowing athletes was dominated by the ACTN3 577X allele. There were significant differences in the χ 2 test between groups of male athletes. The ACTN3 R577 allele was dominant in female athletes. There were significant differences between PBP and FVC/body weight and ACTN3 genotypes in male athletes by ANOVA, respectively (p < 0.05). A linear regression analysis using FVC and FVC/body weight as dependent variables and ACTN3 genotypes as independent variables based on the ACTN3 577X allele recessive genetic effect showed statistical significance in male athletes (p < 0.05). These results suggested that ACE and ACTN3 gene polymorphisms may be used as biomarkers of genetic traits in Chinese rowing athletes.

Muscle fiber composition is associated with physical performance, with endurance athletes having a high proportion of slow-twitch muscle fibers compared to power athletes. Approximately 45% of muscle fiber composition is heritable, however, single nucleotide polymorphisms (SNP) underlying inter-individual differences in muscle fiber types remain largely unknown. Based on three whole genome SNP datasets, we have shown that the rs236448 A allele located near the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene was associated with an increased proportion of slow-twitch muscle fibers in Russian (n = 151; p = 0.039), Finnish (n = 287; p = 0.03), and Japanese (n = 207; p = 0.008) cohorts (meta-analysis: p = 7.9 × 10−5. Furthermore, the frequency of the rs236448 A allele was significantly higher in Russian (p = 0.045) and Japanese (p = 0.038) elite endurance athletes compared to ethnically matched power athletes. On the contrary, the C allele was associated with a greater proportion of fast-twitch muscle fibers and a predisposition to power sports. CDKN1A participates in cell cycle regulation and is suppressed by the miR-208b, which has a prominent role in the activation of the slow myofiber gene program. Bioinformatic analysis revealed that the rs236448 C allele was associated with increased CDKN1A expression in whole blood (p = 8.5 × 10−15) and with greater appendicular lean mass (p = 1.2 × 10−5), whereas the A allele was associated with longer durations of exercise (p = 0.044) reported amongst the UK Biobank cohort. Furthermore, the expression of CDKN1A increased in response to strength (p < 0.0001) or sprint (p = 0.00035) training. Accordingly, we found that CDKN1A expression is significantly (p = 0.002) higher in the m. vastus lateralis of strength athletes compared to endurance athletes and is positively correlated with the percentage of fast-twitch muscle fibers (p = 0.018). In conclusion, our data suggest that the CDKN1A rs236448 SNP may be implicated in the determination of muscle fiber composition and may affect athletic performance.

To replicate previous genome-wide association study identified sprint-related polymorphisms in 3 different cohorts of top-level sprinters and to further validate the obtained results in functional studies. A total of 240 Japanese, 290 Russians, and 593 Brazilians were evaluated in a case-control approach. Of these, 267 were top-level sprint/power athletes. In addition, the relationship between selected polymorphisms and muscle fiber composition was evaluated in 203 Japanese and 287 Finnish individuals. The G allele of the rs3213537 polymorphism was overrepresented in Japanese (odds ratio [OR]: 2.07, P = .024) and Russian (OR: 1.93, P = .027) sprinters compared with endurance athletes and was associated with an increased proportion of fast-twitch muscle fibers in Japanese (P = .02) and Finnish (P = .041) individuals. A meta-analysis of the data from 4 athlete cohorts confirmed that the presence of the G/G genotype rather than the G/A+A/A genotypes increased the OR of being a sprinter compared with controls (OR: 1.49, P = .01), endurance athletes (OR: 1.79, P = .001), or controls + endurance athletes (OR: 1.58, P = .002). Furthermore, male sprinters with the G/G genotype were found to have significantly faster personal times in the 100-m dash than those with G/A+A/A genotypes (10.50 [0.26] vs 10.76 [0.31], P = .014). The rs3213537 polymorphism found in the CPNE5 gene was identified as a highly replicable variant associated with sprinting ability and the increased proportion of fast-twitch muscle fibers, in which the homozygous genotype for the major allele (ie,the G/G genotype) is preferable for performance.

The effect of cannabinoids on caffeine contractures was investigated in slow and fast skeletal muscle fibers using isometric tension recording. In slow muscle fibers, WIN 55,212-2 (10 and 5 μM) caused a decrease in tension. These doses reduced maximum tension to 67.43 ± 8.07% (P = 0.02, n = 5) and 79.4 ± 14.11% (P = 0.007, n = 5) compared to control, respectively. Tension-time integral was reduced to 58.37 ± 7.17% and 75.10 ± 3.60% (P = 0.002, n = 5), respectively. Using the CB1 cannabinoid receptor agonist ACPA (1 μM) reduced the maximum tension of caffeine contractures by 68.70 ± 11.63% (P = 0.01, n = 5); tension-time integral was reduced by 66.82 ± 6.89% (P = 0.02, n = 5) compared to controls. When the CB1 receptor antagonist AM281 was coapplied with ACPA, it reversed the effect of ACPA on caffeine-evoked tension. In slow and fast muscle fibers incubated with the pertussis toxin, ACPA had no effect on tension evoked by caffeine. In fast muscle fibers, ACPA (1 μM) also decreased tension; the maximum tension was reduced by 56.48 ± 3.4% (P = 0.001, n = 4), and tension-time integral was reduced by 57.81 ± 2.6% (P = 0.006, n = 4). This ACPA effect was not statistically significant with respect to the reduction in tension in slow muscle fibers. Moreover, we detected the presence of mRNA for the cannabinoid CB1 receptor on fast and slow skeletal muscle fibers, which was significantly higher in fast compared to slow muscle fiber expression. In conclusion, our results suggest that in the slow and fast muscle fibers of the frog cannabinoids diminish caffeine-evoked tension through a receptor-mediated mechanism.

Fatigue of the vastus lateralis muscle was studied in healthy well-conditioned students, who differed considerable regarding their muscle fibre type distribution. Muscle force decline during repeated maximum voluntary knee extensions at a constant angular velocity (180 degree X s-1 or rad X s-1), using isokinetic equipment, was taken as the criterion for the degree of fatigue. In an attempt to study quantitative as well as qualitative changes in the EMG pattern, integrated EMG (IEMG) and the frequency of the mean power (MPF), computed from the power spectral density function (PSDF), were analysed. It was found that individuals with muscles made up of a high proportion of fast twitch (FT) muscle fibres demonstrated higher peak knee extension torque, and a greater susceptibility to fatigue than did individuals with muscles mainly composed of slow twitch (ST) muscle fibres. An IEMG decline (p less than 0.01) was demonstrated during 100 contractions in individuals rich in FT fibres. Only a slight, but not significant, reduction in IEMG occurred in individuals with high percentage of ST fibres. Concomitantly, MPF decreased (p less than 0.001) in individuals with a high percentage of FT fibres, while their opposites demonstrated only a slight decrease (non-significant). It is suggested that muscle conctraction failure might also be related to qualitative changes in the motor unit recruitment pattern, and that these changes occur more rapidly in muscles composed of a high proportion of FT muscle fibres than in muscles composed to a high proportion of ST fibres.

In this study, actinin-3 (ACTN3) gene expression was investigated in relation to the feed efficiency phenotype in Bos indicus - Bos taurus crossbred steers. A measure of relative feed efficiency based on residual feed intake relative to predictions from the NRC beef cattle model was analyzed by the use of a mixed linear model that included sire and family nested within sire as fixed effects and age, animal type, sex, condition, and breed as random effects for 173 F2 Nellore-Angus steers. Based on these residual intake observations, individuals were ranked from most efficient to least efficient. Skeletal muscle samples were analyzed from 54 steers in three groups of 18 (high efficiency, low efficiency, and a statistically average group). ACTN3, which encodes a muscle-specific structural protein, was previously identified as a candidate gene from a microarray analysis of RNA extracted from muscle samples obtained from a subset of steers from each of these three efficiency groups. The expression of ACTN3 was evaluated by quantitative reverse transcriptase PCR analysis. The expression of ACTN3 in skeletal muscle was 1.6-fold greater in the inefficient steer group than in the efficient group (p = 0.007). In addition to expression measurements, blocks of SNP haplotypes were assessed for breed or parent of origin effects. A maternal effect was observed for ACTN3 inheritance, indicating that a maternal B. indicus block conferred improved residual feed efficiency relative to the B. taurus copy (p = 0.03). A SNP haplotype analysis was also conducted for m-calpain (CAPN2) and fibronectin 1 (FN1), and a significant breed effect was observed for both genes, with B. indicus and B. taurus alleles each conferring favorable efficiency when inherited maternally (p = 0.03 and p = 0.04). Because the ACTN3 structural protein is specific to fast-twitch (type II) muscle fibers and not present in slow-twitch muscle fibers (type I), muscle samples used for expression analysis were also assayed for fiber type ratio (type II/type I). Inefficient animals had a fast fiber type ratio 1.8-fold greater than the efficient animals (p = 0.027). Because these fiber-types exhibit different metabolic profiles, we hypothesize that animals with a greater proportion of fast-twitch muscle fibers are also less feed efficient.

Muscle fibers, as the fundamental units of muscle tissue, play a crucial role in determining skeletal muscle function through their growth, development, and composition. To investigate changes in muscle fiber types and their regulatory mechanisms in Mongolian horses (MG), Xilingol horses (XL), and Grassland-Thoroughbreds (CY), we conducted histological and bioinformatic analyses on the gluteus medius muscle of these three horse breeds. Immunofluorescence analysis revealed that Grassland-Thoroughbreds had the highest proportion of fast-twitch muscle fibers at 78.63%, while Mongolian horses had the lowest proportion at 57.54%. Whole-transcriptome analysis identified 105 differentially expressed genes (DEGs) in the CY vs. MG comparison and 104 DEGs in the CY vs. XL comparison. Time-series expression profiling grouped the DEGs into eight gene sets, with three sets showing significantly up-regulated or down-regulated expression patterns (p &lt; 0.05). Additionally, 280 differentially expressed long non-coding RNAs (DELs) were identified in CY vs. MG, and 213 DELs were identified in CY vs. XL. A total of 32 differentially expressed microRNAs (DEMIRs) were identified in CY vs. MG, while 44 DEMIRs were found in CY vs. XL. Functional enrichment analysis indicated that the DEGs were significantly enriched in essential biological processes, such as actin filament organization, muscle contraction, and protein phosphorylation. KEGG pathway analysis showed their involvement in key signaling pathways, including the mTOR signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. Furthermore, functional variation-based analyses revealed associations between non-coding RNAs and mRNAs, with some non-coding RNAs targeting genes potentially related to muscle function regulation. These findings provide valuable insights into the molecular basis for the environmental adaptability, athletic performance, and muscle characteristics in horses, offering new perspectives for the breeding of Grassland-Thoroughbreds.

1. The conduction velocities of individual motor axons innervating twitch and slow muscle fibres of the frog were determined by intracellular recording of junctional potentials elicited by stimulating the motor nerves at two different points. 2. In normal pyriformis muscles twitch and slow fibres were found to be innervated by two distinct populations of motor axons. Twitch fibre axons conducted at 10-18-7 m/sec, while the conduction velocities of slow fibre axons ranged from 0-5 to 5 m/sec (at 7-9 degrees C). The thresholds for electrical stimulation were significantly lower in the fast than in the slow axons population. 3. Following denervation by crushing the sciatic nerve fast axons which re-innervated the muscle had lower conduction velocities than normal but could still be identified. These lower conduction velocities were measured proximal to the site of the crush and did not recover over a period of 446 days. 4. Fast motor axons regenerated more quickly than slow axons and re-innervated twitch as well as slow muscle fibres non-selectively. About 1 month later slow axons re-established synaptic contacts with slow (and some twitch) muscle fibres. Simultaneous re-innervation by fast and slow motor axons was occasionally observed in slow muscle fibres. Finally, the slow muscle fibres were innervated by slow axons only, while synapses of fast axons could no longer be found in this type of muscle fibre. 5. Action potentials were observed in denervated as well as in re-innervated slow muscle fibres; they disappeared as re-innervation progressed. 6. It is concluded that non-selective re-innervation of slow muscle fibres is present in the frog; it is, however, a transient phenomenon followed by restoration of the original innervation pattern.

Differential Expression of PTP1D, a Protein Tyrosine Phosphatase with Two SH2 Domains, in Slow and Fast Skeletal Muscle Fibers

Guilherme, JPLF, Egorova, ES, Semenova, EA, Kostryukova, ES, Kulemin, NA, Borisov, OV, Khabibova, SA, Larin, AK, Ospanova, EA, Pavlenko, AV, Lyubaeva, EV, Popov, DV, Lysenko, EA, Vepkhvadze, TF, Lednev, EM, Govorun, VM, Generozov, EV, Ahmetov, II, and Lancha Junior, AH. The A-allele of the FTO gene rs9939609 polymorphism is associated with decreased proportion of slow oxidative muscle fibers and over-represented in heavier athletes. J Strength Cond Res 33(3): 691-700, 2019-The purpose of this study was to explore the frequency of the FTO T > A (rs9939609) polymorphism in elite athletes from 2 cohorts (Brazil and Russia), as well as to find a relationship between FTO genotypes and muscle fiber composition. A total of 677 athletes and 652 nonathletes were evaluated in the Brazilian cohort, whereas a total of 920 athletes and 754 nonathletes were evaluated in the Russian cohort. It was found a trend for a lower frequency of A/A genotype in long-distance athletes compared with nonathletes (odds ratio [OR]: 0.65; p = 0.054). By contrast, it was found an increased frequency of the A-allele in Russian power athletes. The presence of the T/A + A/A genotypes rather than T/T increased the OR of being a Russian power athlete compared with matched nonathletes (OR: 1.45; p = 0.002). Different from that observed in combat sports athletes of lighter weight categories, the A-allele was also over-represented in combat sports athletes of heavier weight categories. The presence of the T/A + A/A genotypes rather than T/T increased the OR of being a combat sports athlete of heavier weight categories compared with nonathletes (OR: 1.79; p = 0.018). Regarding the muscle fibers, we found that carriers of the A/A genotype had less slow-twitch muscle fibers than T-allele carriers (p = 0.029). In conclusion, the A/A genotype of the FTO T > A polymorphism is under-represented in athletes more reliant on a lean phenotype and associated with decreased proportion of slow-twitch muscle fibers, while is over-represented in strength and heavier athletes.

Case-controlled animal study. The aim of this study was to investigate whether multifidus muscle fiber type distribution changes in models of interverbal disc (IVD) degeneration and whether this is resolved by physical activity (PA). The loss of slow type I muscle fibers in the multifidus muscle in people with low back pain is contentious. Data from animal models of IVD degeneration suggest some discrepancies in human studies might be explained by the dependence of slow muscle fiber changes and their underlying mechanisms, on the time since injury and progression of IVD degeneration. It is not yet resolved what changes are apparent once the chronic phase is established. It is also not known whether muscle fiber changes can be resolved by whole body PA. This study aimed to examine slow fiber distribution in the multifidus muscle in models of IVD injury or spontaneous degeneration in animals with or without exposure to PA. Two models of IVD degeneration were used. The first model used a genetically modified mouse (SPARC-null) that spontaneously develops IVD degeneration. The second model involved a surgically induced IVD lesion to induce degeneration. Mice in each study were allocated to housing with or without a running wheel for PA. At 12 months of age, the multifidus muscle was harvested. Slow muscle fiber distribution and the mRNA expression of genes associated with muscle fiber type transformation were examined. The proportion and cross-sectional area of slow muscle fibers were reduced in both models of IVD degeneration compared to controls, without evidence of ongoing fiber transformation. Whole-body PA did not attenuate these alterations. Results confirmed slow muscle fiber loss in the multifidus in the chronic phase of IVD degeneration induced spontaneously and by injury. Whole-body PA did not attenuate changes to muscle fiber distribution. More specific approaches to muscle activation might be required to achieve more complete reversal of muscle fiber changes, with potential implications for therapy in humans.Level of Evidence: N/A.

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±4years) with a history of lifelong (>50years) 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±1years) and age-matched non-exercisers (75±2years). 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. We investigated single muscle fibre size and contractile function among three groups of men: lifelong exercisers (LLE) (n=21, 74±4years), old healthy non-exercisers (OH) (n=10, 75±2years) and young exercisers (YE) (n=10, 25±1years). On average, LLE had exercised ∼5 daysweek-1 for ∼7 hweek-1 over the past 53±6years. 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±2765μm2 ) was 25-40% larger (P<0.001) than YE (6106±1710μm2 ) and OH (5476±2467μm2 ). 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±2659μm2 ) was similar to OH (6237±2525μm2 ; P=0.854), with both groups ∼20% smaller (P<0.001) than YE (7860±1930μm2 ). 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±6.4WL-1 ), LLE (13.9±4.5WL-1 ) and YE (12.4±3.5WL-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.