Journal of Cachexia, Sarcopenia and Muscle最新文献

Background: Sarcopenia is thought to be underlined by age-associated anabolic resistance and dysregulation of intracellular signalling pathways. However, it is unclear whether these phenomena are driven by ageing per se or other confounding factors.

Methods: Lean and healthy young (n = 10, 22 ± 3 years, BMI; 23.4 ± 0.8 kg/m²) and old men (n = 10, 70 ± 3 years, BMI; 22.7 ± 1.3 kg/m²) performed unilateral resistance exercise followed by intake of essential amino acids (EAA). Muscle biopsies were collected from the rested and the exercised leg before, immediately after and 60 and 180 min after EAA intake. Muscle samples were analysed for amino acid concentrations, muscle protein synthesis (MPS) and associated anabolic signalling.

Results: Following exercise, peak plasma levels of EAA and leucine were similar between groups, but the area under the curve was ~11% and ~28% lower in Young (p < 0.01). Absolute levels of muscle EAA and leucine peaked 60 min after exercise, with ~15 and ~21% higher concentrations in the exercising leg (p < 0.01) but with no difference between groups. MPS increased in both the resting (~0.035%·h^-1 to 0.056%·h^-1, p < 0.05) and exercising leg (~0.035%·h^-1 to 0.083%·h^-1, p < 0.05) with no difference between groups. Phosphorylation of S6K1^Thr389 increased to a similar extent in the exercising leg in both groups but was 2.8-fold higher in the resting leg of Old at the 60 min timepoint (p < 0.001). Phosphorylation of 4E-BP1^Ser65 increased following EAA intake and exercise, but differences between legs were statistically different only at 180 min (p < 0.001). However, phosphorylation of this site was on average 78% greater across all timepoints in Old (p < 0.01). Phosphorylation of eEF2^Thr56 was reduced (~66% and 39%) in the exercising leg at both timepoints after EAA intake and exercise, with no group differences (p < 0.05). However, phosphorylation at this site was reduced by ~27% also in the resting leg at 60 min, an effect that was only seen in Old (p < 0.01). Total levels of Rheb (~45%), LAT1 (~31%) and Rag B (~31%) were higher in Old (p < 0.001).

Conclusion: Lean and healthy old men do not manifest AR as evidenced by potent increases in MPS and mTORC1 signalling following EAA intake and exercise. Maintained anabolic sensitivity with age appears to be a function of a compensatory increase in basal levels of proteins involved in anabolic signalling. Therefore, our results suggest that age per se does not appear to cause AR in human skeletal muscle.

Background: Both Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) manifest in cognitive impairment and gait disorders. The precise similarities and differences in gait characteristics and underlying neuroimaging mechanisms remain unclear.

Methods: A total of 399 participants were enrolled: 132 with probable AD, including 98 with mild cognitive impairment due to AD (AD-MCI) and 34 with AD dementia, and 185 with CSVD and 82 healthy controls. CSVD patients with cognitive impairment, including subcortical vascular mild cognitive impairment (svMCI) and subcortical vascular dementia, were grouped as subcortical vascular cognitive impairment (SVCI). Voxel-based morphology analysis assessed grey matter volume (GMV), while cerebral blood flow (CBF) was derived from 3D-arterial spin labelling data. Gait metrics included the timed up and go (TUG) test, dual-task TUG (DTUG) test, Berg balance scale (BBS), dual-task cost (DTC), step length, gait speed, cadence and coefficient of variation of gait. The relationships among structural and perfusion variations, gait metrics and cognitive function were examined.

Results: SVCI patients exhibited greater gait impairments and variability than those with AD, while AD patients experienced higher DTC (p < 0.05). These differences were most evident in the MCI stage. In AD, gait speed correlated with GMV in the left middle occipital gyrus (F = 6.149), middle temporal gyrus (F = 4.595), right precuneus (F = 5.174) and other regions (all p < 0.025). In SVCI, gait speed was linked to thalamic GMV (F = 6.004, p < 0.025). Altered CBF in the parietal lobe and precuneus was associated with DTUG (F = 5.672), gait speed (F = 4.347) and BBS (F = 4.153) in AD, while cerebellar CBF related to TUG (F = 6.042), DTUG (F = 4.857) and BBS (F = 7.097) in SVCI (all p < 0.025). In AD-MCI, memory mediated the effect of hippocampal volume on DTC (indirect effect: -2.432, 95% CI [-5.503, -0.438]), while executive function (indirect effect: -2.920, 95% CI [-7.227, -0.695]) and processing speed (indirect effect: -2.286, 95% CI [-5.174, -0.484]) mediated the effect on DTUG. In svMCI, executive function mediated the effect of thalamic volume on step length (indirect effect: 2.309, 95% CI [0.486, 4.685]) and gait speed (indirect effect: 2.029, 95% CI [0.142, 4.588]), while processing speed mediated the effect on step length (indirect effect: 1.777, 95% CI [0.311, 4.021]).

Conclusions: Different gait disorder characteristics and mechanisms were observed in AD and CSVD patients. In AD, gait is associated with volume/perfusion in posterior brain regions, whereas in SVCI, it relates to thalamic volume and cerebellar perfusion. Cognitive impairment mediates the effect of hippocampal and thalamic volumes on gait in AD-MCI and svMCI, respectively.