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Background Degeneration of the motoneuron and neuromuscular junction (NMJ) and loss of motor units (MUs) contribute to age-related muscle wasting and weakness associated with sarcopenia. However, these features have not been comprehensively investigated in humans. This study aimed to compare neuromuscular system integrity and function at different stages of sarcopenia, with a particular focus on NMJ stability and MU properties. Methods We recruited 42 young individuals (Y) (aged 25.98 ± 4.6 years; 57% females) and 88 older individuals (aged 75.9 ± 4.7 years; 55% females). The older group underwent a sarcopenia screening according to the revised guidelines of the European Working Group on Sarcopenia in Older People 2. In all groups, knee extensor muscle force was evaluated by isometric dynamometry, muscle morphology by ultrasound and MU potential properties by intramuscular electromyography (iEMG). MU number estimate (iMUNE) and blood samples were obtained. Muscle biopsies were collected in a subgroup of 16 Y and 52 older participants. Results Thirty-nine older individuals were non-sarcopenic (NS), 31 pre-sarcopenic (PS) and 18 sarcopenic (S). A gradual decrease in quadriceps force, cross-sectional area and appendicular lean mass was observed across the different stages of sarcopenia (for all P < 0.0001). Handgrip force and the Short Physical Performance Battery score also showed a diminishing trend. iEMG analyses revealed elevated near fibre segment jitter in NS, PS and S compared with Y (Y vs. NS and S: P < 0.0001; Y vs. PS: P = 0.0169), suggestive of age-related impaired NMJ transmission. Increased C-terminal agrin fragment (P < 0.0001) and altered caveolin 3 protein expression were consistent with age-related NMJ instability in all the older groups. The iMUNE was lower in all older groups (P < 0.0001), confirming age-related loss of MUs. An age-related increase in MU potential complexity was also observed. These observations were accompanied by increased muscle d

Aim: Muscle thickness (MT) measured by ultrasound has been used to estimate cross-sectional area (measured by CT and MRI) at a single time-point. We tested whether MT could be used as a valid marker of MRI determined muscle anatomical cross-sectional area (ACSA) and volume changes following resistance training (RT). Methods: Nine healthy, young, male volunteers (24±2 y.o., BMI 24.1±2.8 kg/m2) had vastus lateralis (VL) muscle volume (VOL) and ACSA mid (at 50% of femur length, FL) assessed by MRI, and VL MT measured by ultrasound at 50% FL. Measurements were taken at baseline and after 12 weeks of isokinetic RT. Differences between baseline and post-training were assessed by Student’s paired t-test. The relationships between MRI and ultrasound measurements were tested by Pearson’s correlation. Results: After RT, MT increased by 7.5±6.1% (p<0.001), ACSAmid by 5.2±5% (p<0.001) and VOL by 5.0±6.9% (p<0.05) (values: means±S.D.). Positive correlations were found, at baseline and 12 weeks, between MT and ACSAmid (r=0.82, p<0.001 and r=0.73, p<0.001, respectively), and between MT and VOL (r=0.76, p < 0.001 and r=0.73, p < 0.001, respectively). The % change in MT with training was correlated with % change in ACSAmid (r=0.69, p = 0.01), but not % change in VOL (r= 0.33, p>0.05). Conclusions: These data support evidence that MT is a reliable index of muscle ACSAmid and VOL at a single time-point. MT changes following RT are associated with parallel changes in muscle ACSAmid but not with the changes in VOL, highlighting the impact of RT on regional hypertrophy.

We recently reported that the greatest distinguishing feature between eccentric (ECC) and concentric (CON) muscle loading lays in architectural adaptations: ECC favors increases in fascicle length (Lf), associated with distal vastus lateralis muscle (VL) hypertrophy, and CON increases in pennation angle (PA). Here, we explored the interactions between structural and morphological remodeling, assessed by ultrasound and dual x‐ray absorptiometry (DXA), and long‐term muscle protein synthesis (MPS), evaluated by deuterium oxide (D2O) tracing technique. Ten young males (23 ± 4 years) performed unilateral resistance exercise training (RET) three times/week for 4 weeks; thus, one‐leg trained concentrically while the contralateral performed ECC exercise only at 80% of either CON or ECC one repetition maximum (1RM). Subjects consumed an initial bolus of D2O (150 mL), while a 25‐mL dose was thereafter provided every 8 days. Muscle biopsies from VL midbelly (MID) and distal myotendinous junction (MTJ) were collected at 0 and 4‐weeks. MPS was then quantified via GC–pyrolysis–IRMS over the 4‐week training period. Expectedly, ECC and CON RET resulted in similar increases in VL muscle thickness (MT) (7.5% vs. 8.4%, respectively) and thigh lean mass (DXA) (2.3% vs. 3%, respectively), albeit through distinct remodeling: Lf increasing more after ECC (5%) versus CON (2%) and PA increasing after CON (7% vs. 3%). MPS did not differ between contractile modes or biopsy sites (MID‐ECC: 1.42 vs. MID‐CON: 1.4% day−1; MTJ‐ECC: 1.38 vs. MTJ‐CON: 1.39% day−1). Muscle thickness at MID site increased similarly following ECC and CON RET, reflecting a tendency for a contractile mode‐independent correlation between MPS and MT (P = 0.07; R2 = 0.18). We conclude that, unlike MT, distinct structural remodeling responses to ECC or CON are not reflected in MPS; the molecular mechanisms of distinct protein deposition, and/or the role of protein breakdown in mediating these responses remain to be defined.

Aim: Muscle thickness (MT) measured by ultrasound has been used to estimate cross-sectional area (measured by CT and MRI) at a single time-point. We tested whether MT could be used as a valid marker of MRI determined muscle anatomical cross-sectional area (ACSA) and volume changes following resistance training (RT). Methods: Nine healthy, young, male volunteers (24±2 y.o., BMI 24.1±2.8 kg/m2) had vastus lateralis (VL) muscle volume (VOL) and ACSA mid (at 50% of femur length, FL) assessed by MRI, and VL MT measured by ultrasound at 50% FL. Measurements were taken at baseline and after 12 weeks of isokinetic RT. Differences between baseline and post-training were assessed by Student’s paired t-test. The relationships between MRI and ultrasound measurements were tested by Pearson’s correlation. Results: After RT, MT increased by 7.5±6.1% (p<0.001), ACSAmid by 5.2±5% (p<0.001) and VOL by 5.0±6.9% (p<0.05) (values: means±S.D.). Positive correlations were found, at baseline and 12 weeks, between MT and ACSAmid (r=0.82, p<0.001 and r=0.73, p<0.001, respectively), and between MT and VOL (r=0.76, p < 0.001 and r=0.73, p < 0.001, respectively). The % change in MT with training was correlated with % change in ACSAmid (r=0.69, p = 0.01), but not % change in VOL (r= 0.33, p>0.05). Conclusions: These data support evidence that MT is a reliable index of muscle ACSAmid and VOL at a single time-point. MT changes following RT are associated with parallel changes in muscle ACSAmid but not with the changes in VOL, highlighting the impact of RT on regional hypertrophy.

We recently reported that the greatest distinguishing feature between eccentric (ECC) and concentric (CON) muscle loading lays in architectural adaptations: ECC favors increases in fascicle length (Lf), associated with distal vastus lateralis muscle (VL) hypertrophy, and CON increases in pennation angle (PA). Here, we explored the interactions between structural and morphological remodeling, assessed by ultrasound and dual x‐ray absorptiometry (DXA), and long‐term muscle protein synthesis (MPS), evaluated by deuterium oxide (D2O) tracing technique. Ten young males (23 ± 4 years) performed unilateral resistance exercise training (RET) three times/week for 4 weeks; thus, one‐leg trained concentrically while the contralateral performed ECC exercise only at 80% of either CON or ECC one repetition maximum (1RM). Subjects consumed an initial bolus of D2O (150 mL), while a 25‐mL dose was thereafter provided every 8 days. Muscle biopsies from VL midbelly (MID) and distal myotendinous junction (MTJ) were collected at 0 and 4‐weeks. MPS was then quantified via GC–pyrolysis–IRMS over the 4‐week training period. Expectedly, ECC and CON RET resulted in similar increases in VL muscle thickness (MT) (7.5% vs. 8.4%, respectively) and thigh lean mass (DXA) (2.3% vs. 3%, respectively), albeit through distinct remodeling: Lf increasing more after ECC (5%) versus CON (2%) and PA increasing after CON (7% vs. 3%). MPS did not differ between contractile modes or biopsy sites (MID‐ECC: 1.42 vs. MID‐CON: 1.4% day−1; MTJ‐ECC: 1.38 vs. MTJ‐CON: 1.39% day−1). Muscle thickness at MID site increased similarly following ECC and CON RET, reflecting a tendency for a contractile mode‐independent correlation between MPS and MT (P = 0.07; R2 = 0.18). We conclude that, unlike MT, distinct structural remodeling responses to ECC or CON are not reflected in MPS; the molecular mechanisms of distinct protein deposition, and/or the role of protein breakdown in mediating these responses remain to be defined.

Aim: Muscle thickness (MT) measured by ultrasound has been used to estimate cross-sectional area (measured by CT and MRI) at a single time-point. We tested whether MT could be used as a valid marker of MRI determined muscle anatomical cross-sectional area (ACSA) and volume changes following resistance training (RT). Methods: Nine healthy, young, male volunteers (24±2 y.o., BMI 24.1±2.8 kg/m2) had vastus lateralis (VL) muscle volume (VOL) and ACSA mid (at 50% of femur length, FL) assessed by MRI, and VL MT measured by ultrasound at 50% FL. Measurements were taken at baseline and after 12 weeks of isokinetic RT. Differences between baseline and post-training were assessed by Student’s paired t-test. The relationships between MRI and ultrasound measurements were tested by Pearson’s correlation. Results: After RT, MT increased by 7.5±6.1% (p<0.001), ACSAmid by 5.2±5% (p<0.001) and VOL by 5.0±6.9% (p<0.05) (values: means±S.D.). Positive correlations were found, at baseline and 12 weeks, between MT and ACSAmid (r=0.82, p<0.001 and r=0.73, p<0.001, respectively), and between MT and VOL (r=0.76, p < 0.001 and r=0.73, p < 0.001, respectively). The % change in MT with training was correlated with % change in ACSAmid (r=0.69, p = 0.01), but not % change in VOL (r= 0.33, p>0.05). Conclusions: These data support evidence that MT is a reliable index of muscle ACSAmid and VOL at a single time-point. MT changes following RT are associated with parallel changes in muscle ACSAmid but not with the changes in VOL, highlighting the impact of RT on regional hypertrophy.

Aim: Muscle thickness (MT) measured by ultrasound has been used to estimate cross-sectional area (measured by CT and MRI) at a single time-point. We tested whether MT could be used as a valid marker of MRI determined muscle anatomical cross-sectional area (ACSA) and volume changes following resistance training (RT). Methods: Nine healthy, young, male volunteers (24±2 y.o., BMI 24.1±2.8 kg/m2) had vastus lateralis (VL) muscle volume (VOL) and ACSA mid (at 50% of femur length, FL) assessed by MRI, and VL MT measured by ultrasound at 50% FL. Measurements were taken at baseline and after 12 weeks of isokinetic RT. Differences between baseline and post-training were assessed by Student’s paired t-test. The relationships between MRI and ultrasound measurements were tested by Pearson’s correlation. Results: After RT, MT increased by 7.5±6.1% (p<0.001), ACSAmid by 5.2±5% (p<0.001) and VOL by 5.0±6.9% (p<0.05) (values: means±S.D.). Positive correlations were found, at baseline and 12 weeks, between MT and ACSAmid (r=0.82, p<0.001 and r=0.73, p<0.001, respectively), and between MT and VOL (r=0.76, p < 0.001 and r=0.73, p < 0.001, respectively). The % change in MT with training was correlated with % change in ACSAmid (r=0.69, p = 0.01), but not % change in VOL (r= 0.33, p>0.05). Conclusions: These data support evidence that MT is a reliable index of muscle ACSAmid and VOL at a single time-point. MT changes following RT are associated with parallel changes in muscle ACSAmid but not with the changes in VOL, highlighting the impact of RT on regional hypertrophy.

We recently reported that the greatest distinguishing feature between eccentric (ECC) and concentric (CON) muscle loading lays in architectural adaptations: ECC favors increases in fascicle length (Lf), associated with distal vastus lateralis muscle (VL) hypertrophy, and CON increases in pennation angle (PA). Here, we explored the interactions between structural and morphological remodeling, assessed by ultrasound and dual x‐ray absorptiometry (DXA), and long‐term muscle protein synthesis (MPS), evaluated by deuterium oxide (D2O) tracing technique. Ten young males (23 ± 4 years) performed unilateral resistance exercise training (RET) three times/week for 4 weeks; thus, one‐leg trained concentrically while the contralateral performed ECC exercise only at 80% of either CON or ECC one repetition maximum (1RM). Subjects consumed an initial bolus of D2O (150 mL), while a 25‐mL dose was thereafter provided every 8 days. Muscle biopsies from VL midbelly (MID) and distal myotendinous junction (MTJ) were collected at 0 and 4‐weeks. MPS was then quantified via GC–pyrolysis–IRMS over the 4‐week training period. Expectedly, ECC and CON RET resulted in similar increases in VL muscle thickness (MT) (7.5% vs. 8.4%, respectively) and thigh lean mass (DXA) (2.3% vs. 3%, respectively), albeit through distinct remodeling: Lf increasing more after ECC (5%) versus CON (2%) and PA increasing after CON (7% vs. 3%). MPS did not differ between contractile modes or biopsy sites (MID‐ECC: 1.42 vs. MID‐CON: 1.4% day−1; MTJ‐ECC: 1.38 vs. MTJ‐CON: 1.39% day−1). Muscle thickness at MID site increased similarly following ECC and CON RET, reflecting a tendency for a contractile mode‐independent correlation between MPS and MT (P = 0.07; R2 = 0.18). We conclude that, unlike MT, distinct structural remodeling responses to ECC or CON are not reflected in MPS; the molecular mechanisms of distinct protein deposition, and/or the role of protein breakdown in mediating these responses remain to be defined.

Aim: Muscle thickness (MT) measured by ultrasound has been used to estimate cross-sectional area (measured by CT and MRI) at a single time-point. We tested whether MT could be used as a valid marker of MRI determined muscle anatomical cross-sectional area (ACSA) and volume changes following resistance training (RT). Methods: Nine healthy, young, male volunteers (24±2 y.o., BMI 24.1±2.8 kg/m2) had vastus lateralis (VL) muscle volume (VOL) and ACSA mid (at 50% of femur length, FL) assessed by MRI, and VL MT measured by ultrasound at 50% FL. Measurements were taken at baseline and after 12 weeks of isokinetic RT. Differences between baseline and post-training were assessed by Student’s paired t-test. The relationships between MRI and ultrasound measurements were tested by Pearson’s correlation. Results: After RT, MT increased by 7.5±6.1% (p<0.001), ACSAmid by 5.2±5% (p<0.001) and VOL by 5.0±6.9% (p<0.05) (values: means±S.D.). Positive correlations were found, at baseline and 12 weeks, between MT and ACSAmid (r=0.82, p<0.001 and r=0.73, p<0.001, respectively), and between MT and VOL (r=0.76, p < 0.001 and r=0.73, p < 0.001, respectively). The % change in MT with training was correlated with % change in ACSAmid (r=0.69, p = 0.01), but not % change in VOL (r= 0.33, p>0.05). Conclusions: These data support evidence that MT is a reliable index of muscle ACSAmid and VOL at a single time-point. MT changes following RT are associated with parallel changes in muscle ACSAmid but not with the changes in VOL, highlighting the impact of RT on regional hypertrophy.

We recently reported that the greatest distinguishing feature between eccentric (ECC) and concentric (CON) muscle loading lays in architectural adaptations: ECC favors increases in fascicle length (Lf), associated with distal vastus lateralis muscle (VL) hypertrophy, and CON increases in pennation angle (PA). Here, we explored the interactions between structural and morphological remodeling, assessed by ultrasound and dual x‐ray absorptiometry (DXA), and long‐term muscle protein synthesis (MPS), evaluated by deuterium oxide (D2O) tracing technique. Ten young males (23 ± 4 years) performed unilateral resistance exercise training (RET) three times/week for 4 weeks; thus, one‐leg trained concentrically while the contralateral performed ECC exercise only at 80% of either CON or ECC one repetition maximum (1RM). Subjects consumed an initial bolus of D2O (150 mL), while a 25‐mL dose was thereafter provided every 8 days. Muscle biopsies from VL midbelly (MID) and distal myotendinous junction (MTJ) were collected at 0 and 4‐weeks. MPS was then quantified via GC–pyrolysis–IRMS over the 4‐week training period. Expectedly, ECC and CON RET resulted in similar increases in VL muscle thickness (MT) (7.5% vs. 8.4%, respectively) and thigh lean mass (DXA) (2.3% vs. 3%, respectively), albeit through distinct remodeling: Lf increasing more after ECC (5%) versus CON (2%) and PA increasing after CON (7% vs. 3%). MPS did not differ between contractile modes or biopsy sites (MID‐ECC: 1.42 vs. MID‐CON: 1.4% day−1; MTJ‐ECC: 1.38 vs. MTJ‐CON: 1.39% day−1). Muscle thickness at MID site increased similarly following ECC and CON RET, reflecting a tendency for a contractile mode‐independent correlation between MPS and MT (P = 0.07; R2 = 0.18). We conclude that, unlike MT, distinct structural remodeling responses to ECC or CON are not reflected in MPS; the molecular mechanisms of distinct protein deposition, and/or the role of protein breakdown in mediating these responses remain to be defined.