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The relative contributions of intrinsic and extrinsic neuromuscular factors on sarcopenia are poorly understood. The associations among age-related declines of strength, muscle mass, and muscle quality in response to motor unit (MU) loss have not been systematically investigated in the same groups of subjects. The purpose was to assess MU loss, MRI-derived muscle cross-sectional area (CSA), muscle protein quantity (MPQ), and normalized strength of the dorsiflexors in one group of young (~25 years) adult males compared with two groups of healthy men aged 60–85 years. Muscle strength was assessed on a dynamometer and was ~25 % lower in both older groups, but CSA was less only in the older (>75 years) men, with no differences between the young and old (60–73 years). Normalized strength tended to be lower in both groups of aged men compared to young. For MPQ, only the older men showed ~8 % lower values than the young and old men. Older men had fewer functioning MUs than old, and both groups of aged men had fewer MUs than young men. Muscle quality appears to be maintained in the old likely due to compensatory MU remodeling, but in the older group (>75 years), MU loss was higher and MPQ was lower.

Gastrocnemius muscle phosphocreatine ([PCr]) and hydrogen ion ([H(+)]) were measured using (31)P-magnetic resonance spectroscopy during repeated bouts of 10-s heavy-intensity (HI) exercise and 5-s rest compared with continuous (CONT) HI exercise. Recreationally active male subjects (n = 7; 28 yr ± 9 yr) performed on separate occasions 12 min of isotonic plantar flexion (0.75 Hz) CONT and intermittent (INT; 10-s exercise, 5-s rest) exercise. The HI power output in both CONT and INT was set at 50% of the difference between the power output associated with the onset of intracellular acidosis and peak exercise determined from a prior incremental plantar flexion protocol. Intracellular concentrations of [PCr] and [H(+)] were calculated at 4 s and 9 s of the work period and at 4 s of the rest period in INT and during CONT exercise. [PCr] and [H(+)] (mean ± SE) were greater at 4 s of the rest periods vs. 9 s of exercise over the course of the INT exercise bout: [PCr] (20.7 mM ± 0.6 vs. 18.7 mM ± 0.5; P < 0.01); [H(+)] (370 nM ± 13.50 vs. 284 nM ± 13.6; P < 0.05). Average [H(+)] was similar for CONT vs. INT. We therefore suggest that there is a glycolytic contribution to ATP recovery during the very short rest period (<5 s) of INT and that the greater average power output of CONT did not manifest in greater [H(+)] and greater glycolytic contribution compared with INT exercise.

Muscle pull and weight-bearing are key mechanical determinants of bone geometry which is an important feature of bone strength that declines with adult aging. However, the relative importance of these determinants in young and old adults has not been evaluated systematically. To differentiate the influence of each type of mechanical loading we compared humeral and femoral bone shaft geometry and cross-sectional area (CSA) of the arm and thigh muscles in young and old men. Contiguous transverse MRI (Siemens 1.5T) scans of the arm and thigh were made in 10 young men (21.9 ± 1.0 years) and 10 old men (78.1 ± 4.9 years). Image analysis yielded total (TA), cortical (CA) and medullary (MA) CSA of the humeral and femoral shafts, as well as muscle CSA of the corresponding regions of the arm and thigh. Humeral CA was significantly greater in the young, whereas humeral and femoral MA were significantly greater in the older group. Significant correlations were found between arm muscle CSA and humeral CA (r = 0.73); between thigh muscle CSA and femoral CA (r = 0.69); and between body mass and femoral CA (r = 0.63) and TA (r = 0.55). Moderate correlations between muscle CSA and CA suggest that muscle pull is an important determinant of bone geometry. The significant difference observed between young and old in humeral, but not femoral CA, and the correlation between body mass and femoral, but not humeral cortical area, suggests that weight-bearing attenuates bone loss associated with adult aging.

Bone geometry is an important measure of bone strength and is known to be affected by weight-bearing and adult ageing. Engagement in weight-bearing activity decreases with age, thus in this study we compared bone geometry changes between weight-bearing (tibia) and non-weight-bearing (fibula) leg bones in three different age groups of women. Magnetic resonance images of the right leg were acquired in 9 young (20–27 years), 7 old (61–69 years) and 7 very old (71–80 years) women. Total and cortical bone volumes and medullary cavity volumes (mm3) were calculated at proximal and distal sites for both bones. Tibial cortical bone volume was significantly less at the proximal site in old (17%) and very old (24%) groups versus young subjects. Cortical bone volume in the proximal fibula was also significantly reduced in the older groups (7 and 12%), but to a substantially lesser extent than in the tibia. In contrast, distal bone geometry appeared largely to be conserved in both tibia and fibula. Proximally, medullary cavity volume was greater in the older groups in the tibia but not the fibula. Distally, the only difference found in either bone was a significantly greater fibular medullary cavity in the very old group. These findings suggest weight-bearing bones in women are more susceptible than non-weight-bearing bones to age-related changes in bone geometry likely due to decreases in weight-bearing activities. Also, weight-bearing activity appears to provide a greater osteogenic stimulus at the distal portions of the leg bones.

Healthy adult aging is associated with a loss of muscle mass, known as sarcopenia, and functional alterations within the neuromuscular system. As a result, older adults exhibit less strength and slower voluntary contractile velocity. However, these parameters have not been studied fully in older women. PURPOSE: To determine the effect of aging on voluntary isometric strength and contraction velocity of the leg muscles of young (Y), old (O) and very old (VO) women. METHODS: Cross-sectional areas (CSAs) of the anterior and posterior compartments of the right leg were assessed with 3T magnetic resonance (MR) imaging in seven Y (23±2y), five O (65±4y) and six VO (76±3y) women. Maximal voluntary isometric contraction (MVC) torque and maximal contraction velocity (at a fixed load of ∼1Nm) of the dorsiflexors and plantar flexors were determined using a Biodex dynamometer. To determine normalized strength, MVC torque was expressed relative to muscle CSA. RESULTS: Anterior compartment CSA was ∼27% and ∼19% less in the VO compared with the Y and O, respectively, but there was no difference between the Y and O women. The VO had a ∼16% lower dorsiflexor MVC torque than the Y, but neither group differed significantly from the O women. No differences existed among groups for normalized dorsiflexor strength. Maximal voluntary contraction velocity was ∼15% less in the VO than the Y with no other group differences. In the posterior compartment, CSA was 25% less in the VO compared with the Y, but the O did not differ from either Y or VO. Similarly, plantar flexor MVC torque was ∼32% less in the VO compared with the Y women but not different between Y and O, or O and VO. Normalized plantar flexor strength was equivalent among the groups. The VO were 13% slower than the Y for plantar flexor maximal contraction velocity with no other differences between groups. CONCLUSIONS: Lower maximal strength observed in the dorsiflexors and plantar flexors of the VO women can be accounted for by an age-related decrease in muscle mass. Also, contraction velocity did not slow until the 8th decade of life and was similar for both the dorsiflexor and plantar flexor muscle groups. Supported by NSERC.

This study examined the effects of NH4Cl ingestion on phosphocreatine (PCr) metabolism during 9 min of moderate- (MOD) and heavy- (HVY) intensity constant-load isotonic plantar-flexion exercise. Healthy young adult male subjects (n = 8) completed both a control (CON) and NH4Cl ingestion (ACID) trial. Phosphorus-31 magnetic resonance spectroscopy was used to monitor changes in intracellular pH (pHi), [Pi], [PCr], and [ATP]. During the Middle (3–6 min) and Late (6–9 min) stages of HVY, ACID was associated with a higher (P < 0.05) intracellular hydrogen-ion concentration ([H+]i) [Middle: 246 (SD 36) vs. 202 (SD 36) mmol/l]; [Late: 236 (SD 35) vs. 200 (SD 39) mmol/l]. In addition, ACID was associated with a lower (P < 0.05) [PCr] relative to CON during the Early (0–3 min) [18.1 (SD 5.1) vs. 20.4 (SD 5.4) mmol/l] and Middle stages [14.1 (SD 5.4) vs. 16.7 (SD 6.0) mmol/l] of HVY. The amplitude of the primary component of PCr breakdown during the transition to HVY was greater in ACID than CON [14.5 (SD 5.8 vs. 11.3 (SD 4.8) mmol/l], however, the PCr slow component (continued slow decline in [PCr]) showed no difference (P > 0.05). The time constant for PCr breakdown (τPCr) was greater in HVY than MOD for both conditions [58 (SD 22) vs. 28 (SD 15) s ACID; 51 (SD 20) vs. 29 (SD 14) s CON] (P < 0.05). In summary, ACID increased PCr breakdown during the transition from MOD to HVY, but did not increase the magnitude of the PCr slow component.

In this study, we examined muscle metabolic and acid-base status during incremental wrist extension exercise in the forearm of individuals with work-related myalgia (WRM). Eighteen women employed in full-time occupations involving repetitive forearm labor were recruited in this cross-sectional study. Nine of these women were diagnosed with WRM, while the other nine had no previous WRM history and were used as age-matched controls (Con). Phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) was used to noninvasively monitor the intracellular concentrations of phosphocreatine ([PCr]) and inorganic phosphate ([P(i)]) as well as intracellular pH (pH(i)) status during exercise in WRM and Con. We observed a 38% decreased work capacity in WRM compared with Con [0.18 W (SD 0.03) vs. 0.28 W (SD 0.10); P = 0.007]. Piecewise linear regression of the incremental exercise data revealed that the onset of a faster decrease in pH(i) (i.e., the pH threshold, pHT) and the onset of a faster increase in log([P(i)]/[PCr]) (i.e., the phosphorylation threshold, PT) occurred at a 14% relatively lower power output in WRM [pHT: 45.2% (SD 5.3) vs. 59.0% (SD 4.6), P < 0.001; PT: 44.8% (SD 4.3) vs. 57.8% (SD 3.1), P < 0.001; % of peak power output, Con vs. WRM, respectively]. Monoexponential modeling of the kinetics of [PCr] and pH(i) recovery following exercise demonstrated a slower (P = 0.005) time constant (tau) for [PCr] in WRM [113 s (SD 25)] vs. Con [77 s (SD 23)] and a slower (P = 0.007) tau for pH(i) in WRM [370 s (SD 178)] vs. Con [179 s (SD 52)]. In conclusion, our results suggest that WRM is associated with an increased reliance on nonoxidative metabolism. Possible mechanisms include a reduction in local muscle blood flow and perfusion, an increased ATP cost of force production, or both.

Bone geometry is an important determinant of bone strength and is influenced by muscle pull and weight-bearing. Muscle mass and exposure to weight-bearing decrease with age and thus the purpose of the study was to compare bone geometry of the weight-bearing (tibia) and non-weight-bearing (fibula) bones of the leg in different age groups. Magnetic resonance images of the right leg were acquired in 13 young (26 yr), 13 old (66 yr), and 13 very old men (83 yr). Cortical, medullary and total cross-sectional areas (CSA) of the bones were measured at approximately one-third and two-thirds the length of the leg. Muscle CSA of the anterior, lateral and posterior compartments was measured at the proximal site. Cortical CSA was ~14 to 22% smaller in the elderly in the tibia but similar across age in the fibula. Medullary CSA was larger with age (~5 to 65%) in both bones but ~15 to 440% greater in the tibia than fibula. Total CSA was similar across age in both bones. Muscle mass was similar between young and old but ~25% less in the very old and as a consequence, the magnitude of differences in bone geometry at proximal and distal sites varied in the two elderly groups. These findings indicate that there is a complex age-dependent interaction between muscle pull and weight-bearing. The greater age-related differences in bone geometry in the tibia suggest the weight-bearing role of the tibia makes it more susceptible than the fibula to the reduced activity typically associated with aging.

Little is known about the muscle metabolic status during repeated bouts of very short work-to-rest transitions. PURPOSE:: In the present study, we measured gastrocnemius muscle [PCr] and [H+] using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) during repeated bouts of 10 s heavy-intensity exercise and 5 s rest compared to continuous (i.e. no rest) heavy-intensity exercise. METHODS: Recreationally active male subjects (n=8, 27yr±SE3.3) performed on separate occasions 12 min of isotonic plantar flexion (contraction rate 0.75 Hz) continuously (CON) and intermittently (INT) 10 s exercise 5 s rest. Heavy-intensity exercise workload in both CON and INT was set at 150% of the power output associated with the onset of intracellular acidosis determined from a prior incremental plantar flexion exercise protocol. Intracellular concentrations of [H+] and [PCr] were calculated at 4 s and 9 s of the work period and 4 s of the rest period in INT, and at similar intervals during CON. ATP synthesis and oxidative flux were estimated from changes in those concentrations. RESULTS: Metabolite concentrations (mean ±SE) were increased at 4 s of the rest periods vs 9 s of exercise averaged over the course of the intermittent exercise bout: [PCr] (19.09 mM ±0.59 vs 17.33mM ±0.5: p<0.01); [H+] (324.5 nM±13.50 vs 284.0 nM±13.6; p<0.05). Average [H+] was greater for continuous exercise vs interval exercise (252.6nM±5.6 vs 217.18nM±6.5, p< 0.001) during the exercise bout. CONCLUSIONS: A 5 s recovery period is sufficient duration to increase [PCr] and [H+] between repeated 10 s bouts of heavy-intensity exercise. We therefore suggest a rapid shift of the creatine kinase reaction occurs during a very short rest period (<5 s) following a brief bout of heavy intensity exercise. We also observe that the lower average [H+] during short interval exercise suggests reduced production or increased buffering vs continuous exercise of a similar duration and intensity.

Intracellular acidosis has been shown to increase the time constant and/or rate constant of the phosphocreatine (PCr) kinetic response during recovery from exercise, supporting the notion that mitochondrial respiration is reduced under low pH conditions. The slowed PCr recovery in the presence of intracellular acidosis has also been attributed to an increased ATP consumption by cellular ion pumps, and/or to a pH-induced shift in the creatine kinase (CK) equilibrium. However, during this recovery period, [PCr] often rises transiently above resting values before returning to pre-exercise values. This phenomenon has been named the PCr recovery overshoot, and the mechanisms responsible for it remain unknown. PURPOSE: To examine the effects of ammonium chloride (NH4Cl) ingestion on PCr recovery and the magnitude of PCr overshoot following heavy-intensity plantar flexion (PF) exercise. METHODS: Eight untrained male subjects performed isotonic PF exercise in a control (CON) and NH4Cl ingestion (ACID) trial (0.3g/kg oral dose of NH4Cl, over 3 hrs prior to exercise). PF exercise (contraction rate, 0.5 Hz) was performed for 9 min each during moderate- (MOD: 75% of intracellular pH threshold, TpHi) and heavy-intensity exercise (HVY: 125% TpHi), and was followed immediately by 15 min resting recovery. 31phosphorus magnetic resonance spectroscopy was used to non-invasively monitor changes in intracellular pH (pHi), [PCr], and [ATP]. RESULTS: End HVY exercise pHi was lower (P<0.05) in ACID (6.61 (0.07); mean (SD)) than CON (6.69 (0.06)). During recovery the PCr time constant (tPCr) was greater (P<0.05) in ACID (45 s (16)) than CON (33 s (10)). The magnitude of [PCr] recovery overshoot, as a percentage of the pre-exercise resting value, was greater (P<0.05) in ACID than CON during the following recovery periods: 3-6 min (ACID, 110% (3); CON, 107% (3)); 6-9 min (ACID, 110% (3); CON, 106% (4)); 9-12 min (ACID, 108% (3); CON, 105% (3)); and 12-15 min (ACID, 108% (3); CON, 105% (4)). CONCLUSION: A greater intracellular acidosis at the end of HVY was seen in ACID vs. CON. This was associated with a longer time constant describing PCr recovery kinetics and a greater magnitude of [PCr] overshoot above baseline values.

The purpose of this study was to examine the kinetics of phosphocreatine (PCr) breakdown in repeated bouts of heavy-intensity exercise separated by three different durations of resting recovery. Healthy young adult male subjects (n = 7) performed three protocols involving two identical bouts of heavy-intensity dynamic plantar flexion exercise separated by 3, 6, and 15 min of rest. Muscle high-energy phosphates and intracellular acid-base status were measured using phosphorus-31 magnetic resonance spectroscopy. In addition, the change in concentration of total haemoglobin (Delta[Hb(tot)]) and deoxy-haemoglobin (Delta[HHb]) were monitored using near-infrared spectroscopy. Prior exercise resulted in an elevated (P < 0.05) intracellular hydrogen ion ([H+](i)) after 3 min (182 +/- 72 (SD) nM; pH 6.73) and 6 min (112 +/- 19 nM; pH 6.95) but not after 15 min (93 +/- 8 nM; pH 7.03) compared to pre-exercise in Con (90 +/- 3 nM; pHi 7.05). The on-transient time constant (tau) of the PCr primary component was not different amongst the exercise bouts. However, in each of the subsequent bouts the amplitude of the PCr slow component, total PCr breakdown, and rise in [H+](i) were reduced (P < 0.05). At exercise onset, Delta[Hb(tot)] was increased (P < 0.05) and the Delta[HHb] kinetic response was slowed (P < 0.05) in the exercise after 3 min, consistent with improved muscle perfusion. In summary, neither the level of acidosis or muscle perfusion at the onset of exercise appeared to be directly related to the time course of the on-transient PCr primary component or the magnitude of the PCr slow component during subsequent bouts of exercise.

It is well established that changes in bone geometry occur with age. However, there has been little investigation about the influence of weight-bearing load on the magnitude of these changes. PURPOSE: To assess the impact of aging on cross-sectional areas of the main weight-bearing (tibia) and minimally weight-bearing (fibula) bones of the leg. METHODS: Serial transverse magnetic resonance images of the right leg were acquired in 13 young (26 ± 3y), 13 old (66 ± 2y), and 13 very old men (83 ± 4y) of similar heights and weights. Cortical area (CA) and medullary area (MA) of the tibia and fibula were measured for 5 images (7mm slice thickness, 3mm slice offset) centered one-third of the distance between the head of the fibula and the lateral malleolus. Total area (TA) for each image was calculated as the sum of CA and MA, and the relative percentage of cortical bone (CORT) was calculated as CA divided by TA. The mean of the 5 images was used for all statistical comparisons; significance set at P<0.05. RESULTS: In the tibia, CA was greater in young (434mm2) than old (377mm2) and very old (340mm2), whereas MA was greater in very old (265mm2) than young (178mm2); old (211mm2). Total bone was not different among the age groups (612, 588, and 604mm2 for young, old, and very old, respectively). Young and old had higher percentages (70% and 65%, respectively) of CORT than did the very old (57%), with no difference between young and old. In the fibula, CA was greater in young (109mm2) than very old (93mm2); old (95mm2). Medullary area was greater in very old (40mm2) than young (25mm2) and old (27mm2). Similar to the tibia, total bone of the fibula was unchanged with age (134, 122, and 133mm2 for young, old, and very old, respectively), and CA expressed as a percentage of the TAwas higher in young and old (81 % and 78%, respectively) as compared to very old (70%). CONCLUSION: Age-related decreases in CA and increases in MA led to a progressive decline in the relative percentage of CORT in both the tibia and fibula. These findings indicate that the weight-bearing role of the tibia does not prevent the age-related loss of CORT. In fact, the relative loss of CORT was slightly greater in the tibia than fibula which suggests that the weight-bearing role of the tibia makes it more susceptible than the fibula to the reduced activity typically associated with aging. Supported by NSERC