Biology subjects

Soendenbroe, C.

Publications and source records attributed to Soendenbroe, C..

4 recordsLinked to original sources

bioRxiv2025

Heavy Resistance Exercise Training in Older Men: A Responder and Inter-individual Variability Analysis

BackgroundHeavy resistance exercise training (HReT) effectively increases muscle mass and strength in groups of older individuals. However, the extent of inter-individual variability in response to HReT, and the possible existence of non-responders, remains unclear. The primary aim was to determine the presence of inter-individual variability in the response to prolonged HReT in healthy older individuals. Secondary aims were to classify individual responsiveness using a combination of gold-standard assessment methods, and to explore training progression and baseline levels as possible response moderators. MethodsWe conducted a secondary analysis of an 8- and 16-week intervention of thrice weekly HReT (EX) or continuation of a sedentary lifestyle (SED). 58 healthy men (age 72{+/-}5) were randomized into EX (n=38) or SED (n=20). Assessments were conducted at baseline, mid-intervention (8wk), and post-intervention (16wk) for five outcomes: Maximal voluntary contraction strength (MVC), rate of force development (RFD), quadriceps cross-sectional area (qCSA), and type I and II myofibre cross-sectional area (fCSA). Training compliance and progression (as measured by 1-repetition maximum (1RM)) were monitored. Inter-individual variability was assessed using the standard deviation of individual responses (SDIR). Individual change scores relative to a Typical Error (TE) were used to classify individuals as Poor, Trivial, Robust or Excellent responders. ResultsAt the group level, EX increased MVC, RFD, qCSA and type II fCSA by 19{+/-}14 %, 58{+/-}80 %, 3{+/-}4 % and 14{+/-}25 %, respectively, with no changes in SED. Inter-individual variability was observed for all outcomes. Individual responses to HReT were outcome- and time-dependent, with 31 participants (82%) being classified as Robust or Excellent responders, and two participants (5%) being Poor responders, following 16wk of HReT. Training compliance and 1RM progression did not account for the observed response variability following HReT. Lower baseline levels were associated with greater improvements; however, this did not account for the observed inter-individual variability. ConclusionsThis study provides strong evidence of inter-individual variability in response to HReT among healthy older men. Given the rarity of true non-responders, HReT should remain the universally recommended first-line strategy for enhancing muscle mass and strength in this population.

physiology↗

bioRxiv2024

Muscle Fibroblasts and Stem Cells Stimulate Motor Neurons in An Age and Exercise-Dependent Manner

Exercise preserves neuromuscular function in ageing through unknown mechanisms. Skeletal muscle fibroblasts (FIB) and stem cells (MuSC) are abundant in skeletal muscle and reside close to neuromuscular junctions, but their relative roles in motor neuron maintenance remain undescribed. Using direct co-cultures of embryonic rat motor neurons with either human MuSC or FIB, RNA sequencing revealed profound differential regulation of the motor neuron transcriptome, with FIB generally favoring neuron growth and cell migration and MuSC favoring production of ribosomes and translational machinery. Conditioned medium from FIB was superior to MuSC in preserving motor neurons and increasing their maturity. Lastly, we established the importance of donor age and exercise status and found an age-related distortion of motor neuron and muscle cell interaction that was fully mitigated by lifelong physical activity. In conclusion, we show that human muscle FIB and MuSC synergistically stimulate the growth and viability of motor neurons, which is further amplified by regular exercise.

physiology↗

bioRxiv2023

Marked irregular myofiber shape is a hallmark of human skeletal muscle aging and is reversed by heavy resistance training

BackgroundAge-related loss of strength is disproportionally greater than the loss of mass, suggesting maladaptations in the neuro-myo-tendinous system. Myofibers are often misshaped in aged and diseased muscle, but systematic analyses of large sample sets are lacking. Our aim was to investigate myofiber shape in relation to age, exercise, myofiber type, species, and sex. MethodsPreviously collected vastus lateralis muscle biopsies (n=265) from 197 males and females, covering an age-span of 20 to 97 years, were examined. The gastrocnemius and soleus muscles of 7 C57BL/6 mice were also examined. Immunofluorescence and ATPase stainings of muscle cross-sections were used to measure myofiber cross-sectional area (CSA) and perimeter, from which a shape factor index (SFI) was calculated in a fiber type specific manner (type I and II in humans; type I, IIa, IIx and IIb in mice). Heavy resistance training (RT) was performed 3 times per week for 3-4 months by a subgroup (n=59). Correlation analyses were performed comparing SFI and CSA with age, muscle mass, maximal voluntary contraction (MVC), rate of force development (RFD), and specific force (MVC/muscle mass). ResultsIn human muscle, SFI was positively correlated with age for both type I (R2=0.20) and type II (R2=0.38) myofibers. When subjects were separated into age cohorts, SFI was lower for type I (p<0.001) and II (p<0.001) myofibers in Young (20-36) compared to Old (60-80), and higher for type I (p<0.05) and II (p<0.001) myofibers in the Oldest Old (>80) compared to Old. The increased SFI in old muscle was observed in myofibers of all sizes. Within all three age cohorts, type II myofibers SFI was higher than for type I myofibers (p<0.001), which was also the case in mice muscles (p<0.001). Across age cohorts, there was no difference between males and females in SFI for either type I (p=0.496/0.734) or II (p=0.176/0.585) myofibers. Multiple linear regression revealed that SFI, after adjusting for age and myofiber CSA, has independent explanatory power for 8 out of 10 indices of muscle mass and function. RT reduced SFI of type II myofibers in both Young and Old (p<0.001). ConclusionsHere, we identify type I and II myofiber shape in humans and mice as a hallmark of muscle ageing, that independently predicts volumetric and functional assessments of muscle health. RT reverts the shape of type II myofibers, indicating that lack of neuromuscular activation might lead to myofiber deformity.

physiology↗

bioRxiv2022

Preponderant Myosin Super-Relaxed State In Skeletal Muscle From Endurance Athletes

It has recently been established that myosin, the molecular motor protein, is able to exist in two conformations in relaxed skeletal muscle. These conformations are known as super-relaxed (SRX) and disordered-relaxed (DRX) states and are finely balanced to optimize skeletal muscle metabo-lism. Indeed, SRX myosins are thought to have a 10-fold reduction in ATP turnover compared to DRX myosins. Here, we investigated whether chronic physical activity in humans would be associated with changes in the proportions of SRX and DRX skeletal myosins. For that, we isolated mus-cle fibres from various athletic and sedentary populations and ran a loaded Mant-ATP chase proto-col. We observed that, in endurance-trained athletes, the amounts of myosin molecules in the SRX state was significantly greater than in age-matched sedentary individuals or than in strength athletes. To further assess whether this change would have an impact on the potency of a SRX-inducing pharmacological compound, Mavacamten, we performed similar analyses as above with and without the drug in muscle fibres from endurance athletes. Surprisingly, we found that 0.3 M of Mava-camten had only marginal effects. Altogether, our results indicate that chronic endurance training-status influences resting skeletal myosin conformations, and Mavacamten potency. Our findings also emphasize that environmental stimuli such as exercise can re-wire the molecular metabolism of human skeletal muscle through myosin. SummaryLewis et al., investigate how training-status influences myosin conformations involved in the resting metabolism of skeletal muscle. They find that, in endurance-trained athletes, skeletal myosin preferentially adopts an energy-saving conformation known as super-relaxed state, lowering the metabolic rate and affecting the potency of a super-relaxed state-inducing drug, Mavacamten.

physiology↗