Biology subjects

Hinks, A.

Publications and source records attributed to Hinks, A..

6 recordsLinked to original sources

bioRxiv2024

Residual force enhancement is not altered while force depression is amplified at the cellular level in old age

Residual force enhancement (rFE) and residual force depression (rFD) are history-dependent properties of muscle which refer to increased and decreased isometric force following a lengthening or shortening contraction, respectively. The history-dependence of force is greater in older than younger adults when assessed at the joint level. However, it is unclear whether this amplification of the history-dependence of force in old age is owing to cellular mechanisms or a consequence of age-related remodeling of muscle architecture. Single muscle fibres from the psoas major of old and young F344BN rats were dissected and chemically permeabilized. Single muscle fibres were mounted between a force transducer and length controller, then maximally activated (pCa 4.5). To assess rFD, fibers were actively shortened from 3.1 to 2.5{micro}m at both a slow (0.15Lo/s) and fast (0.6Lo/s) speed, with a fixed-end isometric reference contraction at 2.5{micro}m. To assess rFE, fibers were activated and stretched at 0.3Lo/s from a sarcomere length of 2.2 to 2.5{micro}m, and 2.7 to 3.0{micro}m, and compared to fixed-end isometric reference contractions at 2.5 and 3.0{micro}m, respectively. Isometric force was {approx}19% lower in old as compared with young (p<0.001). Upon normalizing to fibre cross-sectional area, there was no age-related difference in specific force (p>0.05). rFD was {approx}33% greater in old as compared with young (p<0.05), while rFE did not differ between groups (p>0.05). rFD is amplified in old age at the cellular level, while rFE appears to be unchanged, thus previously reported age-related modification of rFE occurs upstream from the cellular level.

physiology↗

bioRxiv2024

Age-related differences in the loss and recovery of serial sarcomere number following disuse atrophy in rats

BackgroundOlder adults exhibit a slower recovery of muscle mass following disuse atrophy than young adults. At a smaller scale, muscle fibre cross-sectional area (i.e., sarcomeres in parallel) exhibits this same pattern. Less is known, however, about age-related differences in the recovery of muscle fibre length, driven by increases in serial sarcomere number (SSN), following disuse. The purpose of this study was to investigate age-related differences in SSN adaptations and muscle mechanical function during and following muscle immobilization. We hypothesized that old rats would experience a similar magnitude of SSN loss during immobilization, however, take longer to recover SSN than young following cast removal, which would limit the recovery of muscle mechanical function. MethodsWe casted the plantar flexors of young (8 months) and old (32 months) male rats in a shortened position for 2 weeks, and assessed recovery during 4 weeks of voluntary ambulation. Following sacrifice, legs were fixed in formalin for measurement of soleus wet weight and SSN with the un-casted soleus acting as a control. Ultrasonographic measurements of pennation angle (PA) and muscle thickness (MT) were also conducted weekly. In-vivo active and passive torque-angle relationships were constructed pre-cast, post-cast, and following 4 weeks of recovery. ResultsFrom pre- to post-cast, young and old rats experienced similar decreases in SSN (-20%, P<0.001), muscle wet weight (-25%, P<0.001), MT (-30%), PA (-15%, P<0.001), and maximum isometric torque (-40%, P<0.001), but there was a greater increase in passive torque in old (+180%, P<0.001) compared to young rats (+68%, P=0.006). Following cast removal, young exhibited quicker recovery of SSN, PA, and MT than old, but SSN recovered sooner than PA and MT in both young and old. Muscle wet weight recovered 90% and active torque fully recovered in young rats, whereas in old these remained unrecovered at 75% and 72%, respectively. ConclusionsThis study showed that old rats retain a better ability to recover longitudinal compared to parallel muscle morphology following cast removal, making SSN a highly adaptable, appealing mechanism for restoration of functional capacity following disuse in elderly populations.

physiology↗

bioRxiv2024

Residual force enhancement decreases when scaling from the single muscle fibre to joint level in humans

Residual force enhancement (rFE), defined as increased isometric force following active lengthening compared to a fixed-end isometric contraction at the same muscle length and level of activation, is present across all scales of muscle. While rFE is always present at the cellular level, often rFE non-responders are observed during joint-level voluntary contractions. We compared rFE between the joint level and single fibre level (vastus lateralis biopsies) in 16 young males. In-vivo voluntary knee-extensor rFE was measured by comparing steady-state isometric torque between a stretch-hold (maximal activation at 150{degrees}, stretch to 70{degrees}, hold) and a fixed-end isometric contraction, with ultrasonographic recording of vastus lateralis fascicle length (FL). Fixed-end contractions were performed at 67.5{degrees}, 70{degrees}, 72.5{degrees}, and 75{degrees}; the joint angle that most closely matched FL of the stretch-hold contractions isometric steady-state was used to calculate rFE. The starting and ending FLs of the stretch-hold contraction were expressed as % optimal FL, determined via torque-angle relationship. In single fibre experiments, the starting and ending fibre lengths were matched relative to optimal length determined from in-vivo testing, yielding an average sarcomere excursion of [~]2.2-3.4{micro}m. There was a greater magnitude of rFE at the single fibre ([~]20%) than joint level ([~]5%) (P=0.004), with non-responders only observed at the joint level. By comparing rFE across scales within the same participants, we show the development of the rFE non-responder phenomenon is upstream of rFEs cellular mechanisms, with rFE only lost rather than gained when scaling from single fibres to the joint level.

physiology↗

bioRxiv2023

Age-related blunting of serial sarcomerogenesis and mechanical adaptations following 2 weeks of maximal eccentric resistance training

BackgroundDuring natural aging, muscles atrophy, which is partly accounted for by a loss of sarcomeres in series. Serial sarcomere number (SSN) is associated with aspects of muscle mechanical function including the force-length and force-velocity-power relationships; hence, the age-related loss of SSN contributes to declining performance. Training emphasizing muscle lengthening (eccentric) contractions increases SSN in young healthy rodents. However, the ability for eccentric training to increase SSN and improve mechanical function in old age is unknown. MethodsTen young (9 months) and 11 old (33 months) Fisher344/BN F1 rats completed 4 weeks of unilateral isokinetic eccentric plantar flexion training 3 days/week. Pre- and post-training, the plantar flexors were assessed for maximum tetanic torque (ankle angles of 70{degrees} and 90{degrees}), the torque-frequency relationship (stimulation frequencies of 1-100 Hz), the passive torque-angle relationship (ankle angles of 110-70{degrees}), and the torque-angular velocity-power relationship (isotonic loads of 10%-80% maximum). Following post-training testing, rats were sacrificed, and the soleus, lateral gastrocnemius (LG), and medial gastrocnemius (MG) were harvested for SSN assessment by measuring sarcomere lengths with laser diffraction, with the untrained leg used as a control. ResultsIn the untrained leg/pre-training, old rats had lower SSN in the soleus (-9%), LG (-7%), and MG (-14%), lower maximum torque (-27 to -42%), power (-63%), and shortening velocity (-35%), and greater passive torque (+62 to +191%) than young. Young rats showed increased SSN from the untrained to the trained soleus and MG. In contrast, old rats had no change in soleus SSN between legs and experienced SSN loss in the LG. Pre- to post-training, young rats saw modest improvements in isometric mechanical function, including a 13% increase in maximum torque at 90{degrees} and 4-11% increases in 10-60 Hz torque. Old rats, however, had reductions in maximum torque (-35%), shortening velocity (-46%), and power (-63%), and increased passive torque (+24 to +51%) from pre- to post-training. ConclusionsEccentric training induced serial sarcomerogenesis and improved mechanical function in young rats, while old rats exhibited dysfunctional remodeling that led to impairments in muscle mechanical performance following training.

physiology↗

bioRxiv2023

Ultrasonographic measurements of fascicle length overestimate adaptations in serial sarcomere number

Ultrasound-derived measurements of muscle fascicle length (FL) are often used to infer increases (chronic stretch or training) or decreases (muscle disuse or aging) in serial sarcomere number (SSN). Whether FL adaptations measured via ultrasound can truly approximate SSN adaptations has not been investigated. We casted the right hindlimb of 15 male Sprague-Dawley rats in a dorsiflexed position (i.e., stretched the plantar flexors) for 2 weeks, with the left hindlimb serving as a control. Ultrasound images of the soleus, lateral gastrocnemius (LG), and medial gastrocnemius (MG) were obtained with the ankle at 90{degrees} and full dorsiflexion for both hindlimbs pre and post-cast. Following post-cast ultrasound measurements, legs were fixed in formalin with the ankle at 90{degrees}, then muscles were dissected, and fascicles were teased out for measurement of sarcomere lengths via laser diffraction and calculation of SSN. Ultrasound detected an 11% increase in soleus FL, a 12% decrease in LG FL, and an 8-11% increase in MG FL for proximal fascicles and at full dorsiflexion. These adaptations were partly reflected by SSN adaptations, with a 6% greater soleus SSN in the casted leg than the un-casted leg, but no SSN differences for the gastrocnemii. Weak relationships were observed between ultrasonographic measurements of FL and measurements of FL and SSN from dissected fascicles. Our results showed that ultrasound-derived FL measurements can overestimate an increase in SSN by [~]5%. Future studies should be cautious when concluding a large magnitude of sarcomerogenesis from ultrasound-derived FL measurements, and may consider applying a correction factor. Key Points SummaryO_LIMeasurements of muscle fascicle length via ultrasound are often used to infer changes in serial sarcomere number, such as increases following chronic stretch or resistance training, and decreases with aging or muscle disuse C_LIO_LIThe present study used a rat model of casting the plantar flexor muscles in a stretched position to investigate directly whether ultrasound-derived fascicle length can accurately detect adaptations in serial sarcomere number C_LIO_LIUltrasound detected an [~]11% increase in soleus fascicle length, but measurements on dissected fascicles showed the actual increase in serial sarcomere number was only [~]6%; therefore, measurements of ultrasound-derived fascicle length can overestimate serial sarcomere number adaptations by as much as 5% C_LI

physiology↗

bioRxiv2022

An increase in serial sarcomere number induced via weighted downhill running improves work loop performance in the rat soleus

Increased serial sarcomere number (SSN) has been observed in rats via downhill running training due to the emphasis on active lengthening contractions; however, little is known about the influence on dynamic contractile function. Therefore, we employed 4 weeks of weighted downhill running training in rats, then assessed soleus SSN and work loop performance. We hypothesized trained rats would produce greater net work output during faster, higher-strain work loops due to a greater SSN. Thirty-one Sprague-Dawley rats were assigned to a control or training group. Weight was added during downhill running via a custom-made vest, progressing from 5-15% body mass. Following sacrifice, the soleus was dissected, and a force-length relationship was constructed. Work loops (active shortening followed by passive lengthening) were then performed about optimal muscle length (LO) at 1.5-3-Hz cycle frequencies and 1-7-mm strains to assess net work output. Muscles were then fixed in formalin at LO. Fascicle lengths and sarcomere lengths were measured and used to calculate SSN. Intramuscular collagen content and crosslinking were quantified via a hydroxyproline content and pepsin-solubility assay. Trained rats had longer fascicle lengths (+13%), greater SSN (+8%), greater specific active forces (+50%), and lower passive forces (-45-62%) than controls (P<0.05). There were no differences in collagen parameters (P>0.05). Net work output was greater (+101-424%) in trained than control rats for the 1.5-Hz loops at 1, 3, and 5-mm strains (P<0.05) and showed relationships with fascicle length (R2=0.14-0.24, P<0.05). These results suggest training-induced longitudinal muscle growth may improve dynamic performance.

physiology↗