Maximum oxidative capacity of skeletal muscle measured by in vivo phosphorus magnetic resonance spectroscopy ( 31 P-MRS) declines with age, and negatively affects whole-body aerobic capacity. However, it remains unclear whether the loss of oxidative capacity is caused by reduced volume and function of mitochondria or limited substrate availability secondary to impaired muscle perfusion. Therefore, we sought to elucidate the role of muscle perfusion on the age-related decline of muscle oxidative capacity and ultimately whole-body aerobic capacity. Muscle oxidative capacity was assessed by 31 P-MRS post-exercise phosphocreatine recovery time (τ PCr ), with higher τ PCr reflecting lower oxidative capacity, in 75 healthy participants (48 men, 22–89 years) of the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing study. Muscle perfusion was characterized as an index of blood volume at rest using a customized diffusion-weighted MRI technique and analysis method developed in our laboratory. Aerobic capacity (peak-VO 2 ) was also measured during a graded treadmill exercise test in the same visit. Muscle oxidative capacity, peak-VO 2 , and resting muscle perfusion were significantly lower at older ages independent of sex, race, and body mass index (BMI). τ PCr was significantly associated with resting muscle perfusion independent of age, sex, race, and BMI ( p -value = 0.004, β = −0.34). τ PCr was also a significant independent predictor of peak-VO 2 and, in a mediation analysis, significantly attenuated the association between muscle perfusion and peak-VO 2 (34% reduction for β in perfusion). These findings suggest that the age-associated decline in muscle oxidative capacity is partly due to impaired muscle perfusion and not mitochondrial dysfunction alone. Furthermore, our findings show that part of the decline in whole-body aerobic capacity observed with aging is also due to reduced microvascular blood volume at rest, representing a basal capacity of the microvascular system, which is mediated by muscle oxidative capacity. This finding suggests potential benefit of interventions that target an overall increase in muscle perfusion for the restoration of energetic capacity and mitochondrial function with aging.
Aging is associated with impaired endothelium-dependent vasodilation that leads to muscle perfusion impairment and contributes to organ dysfunction. Impaired muscle perfusion may result in inadequate delivery of oxygen and nutrients during and after muscle contraction, leading to muscle damage. The ability to study the relationship between perfusion and muscle damage has been limited using traditional muscle perfusion measures, which are invasive and risky. To overcome this limitation, we optimized a diffusion-weighted MRI sequence and validated an intravoxel incoherent motion (IVIM) analysis based on Monte Carlo simulation to study muscle perfusion impairment with aging during post-exercise hyperemia. Simulation results demonstrated that the bias of IVIM-derived perfusion fraction ( f p ) and diffusion of water molecules in extra-vascular tissue (D) ranged from −3.3% to 14% and from −16.5% to 0.002%, respectively, in the optimized experimental condition. The dispersion in f p and D ranged from 3.2% to 9.5% and from 0.9% to 1.1%, respectively. The midthigh of the left leg of four younger (21-30 year old) and four older (60-90 year old) healthy females was studied using the optimized protocol at baseline and at seven time increments occurring every 3.25 min following in-magnet dynamic knee extension exercise performed using a MR-compatible ergometer with a workload of 0.4 bar for 2.5 min. After exercise, both f p and D significantly increased in the rectus femoris (active muscle during exercise) but not in adductor magnus (inactive muscle), reflecting the fact that the local increase in perfusion with both groups showed a maximum value in the second post-exercise time-point. A significantly greater increase in perfusion from the baseline (p < 0.05) was observed in the younger group (37 ± 12.05%) compared with the older group (17.57 ± 15.92%) at the first post-exercise measurement. This work establishes a reliable non-invasive method that can be used to study the effects of aging on dynamic changes in muscle perfusion as they relate to important measures of physical function.
Sarcopenia, the age‐related loss of muscle mass and strength, is linked to a range of adverse outcomes, such as impaired physical performance, cognitive function, and mortality. Preventing sarcopenia may reduce the burden of functional decline with aging and its impact on physiological and economic well‐being in older adults. Mitochondria in muscle cells lose their intrinsic efficiency and capacity to produce energy during aging, and it has been hypothesized that such a decline is the main driver of sarcopenia. Oxidative phosphorylation becomes impaired with aging, affecting muscle performance, and contributing to an age‐associated decline in mobility. However, it is unclear whether this deterioration is due to a reduced mitochondria population, decreased mitochondrial energetic efficiency, or a reduced capacity to dynamically transport oxygen and nutrients into the mitochondria, and addressing these questions is an active area of research. Further research in humans will require use of new “omics” technologies, progress in neuroimaging techniques that permit energy production assessment, and visualization of molecules critical for energetic metabolism, as well as proxy biomarkers of muscle perfusion.
The decrease in skeletal muscle mitochondrial oxidative capacity with age adversely affects muscle strength and physical performance. Factors that are associated with this decrease have not been well characterized. Low plasma lysophosphatidylcholines (LPC), a major class of systemic bioactive lipids, are predictive of aging phenotypes such as cognitive impairment and decline of gait speed in older adults. Therefore, we tested the hypothesis that low plasma LPC are associated with impaired skeletal muscle mitochondrial oxidative capacity. Skeletal muscle mitochondrial oxidative capacity was measured using in vivo phosphorus magnetic resonance spectroscopy (31P‐MRS) in 385 participants (256 women, 129 men), aged 24–97 years (mean 72.5) in the Baltimore Longitudinal Study of Aging. Postexercise recovery rate of phosphocreatine (PCr), kPCr, was used as a biomarker of mitochondrial oxidative capacity. Plasma LPC were measured using liquid chromatography–tandem mass spectrometry. Adults in the highest quartile of kPCr had higher plasma LPC 16:0 (p = 0.04), 16:1 (p = 0.004), 17:0 (p = 0.01), 18:1 (p = 0.0002), 18:2 (p = 0.002), and 20:3 (p = 0.0007), but not 18:0 (p = 0.07), 20:4 (p = 0.09) compared with those in the lower three quartiles in multivariable linear regression models adjusting for age, sex, and height. Multiple machine‐learning algorithms showed an area under the receiver operating characteristic curve of 0.638 (95% confidence interval, 0.554, 0.723) comparing six LPC in adults in the lower three quartiles of kPCr with the highest quartile. Low plasma LPC are associated with impaired mitochondrial oxidative capacity in adults.
Articles you may be interested inHigh temperature spin dynamics in linear magnetic chains, molecular rings, and segments by nuclear magnetic resonance J. Appl. Phys. 117, 17B308 (2015) A detailed experimental investigation of the effects giving rise to the magnetic energy level structure in the vicinity of the level crossing (LC) at low temperature is reported for the open antiferromagnetic molecular ring Cr 8 Zn. The study is conducted by means of thermodynamic techniques (torque magnetometry, magnetization and specific heat measurements) and microscopic techniques (nuclear magnetic resonance line width, nuclear spin lattice, and spin-spin relaxation measurements). The experimental results are shown to be in excellent agreement with theoretical calculations based on a minimal spin model Hamiltonian, which includes a Dzyaloshinskii-Moriya interaction. The first ground state level crossing at µ 0 H c1 = 2.15 T is found to be an almost true LC while the second LC at µ 0 H c2 = 6.95 T has an anti-crossing gap of ∆ 12 = 0.19 K. In addition, both NMR and specific heat measurements show the presence of a level anti-crossing between excited states at µ 0 H = 4.5 T as predicted by the theory. In all cases, the fit of the experimental data is improved by introducing a distribution of the isotropic exchange couplings (J), i.e., using a J strain model. The peaks at the first and second LCs in the nuclear spin-lattice relaxation rate are dominated by inelastic scattering and a value of Γ ∼ 10 10 rad/s is inferred for the life time broadening of the excited state of the open ring, due to spin phonon interaction. A loss of NMR signal (wipe-out effect) is observed for the first time at LC and is explained by the enhancement of the spin-spin relaxation rate due to the inelastic scattering. C 2015 AIP Publishing LLC. [http://dx
Adequate support of energy for biological activities and during fluctuation of energetic demand is crucial for healthy aging; however, mechanisms for energy decline as well as compensatory mechanisms that counteract such decline remain unclear. We conducted a discovery proteomic study of skeletal muscle in 57 healthy adults (22 women and 35 men; aged 23–87 years) to identify proteins overrepresented and underrepresented with better muscle oxidative capacity, a robust measure of in vivo mitochondrial function, independent of age, sex, and physical activity. Muscle oxidative capacity was assessed by 31P magnetic resonance spectroscopy postexercise phosphocreatine (PCr) recovery time (τPCr) in the vastus lateralis muscle, with smaller τPCr values reflecting better oxidative capacity. Of the 4,300 proteins quantified by LC‐MS in muscle biopsies, 253 were significantly overrepresented with better muscle oxidative capacity. Enrichment analysis revealed three major protein clusters: (a) proteins involved in key energetic mitochondrial functions especially complex I of the electron transport chain, tricarboxylic acid (TCA) cycle, fatty acid oxidation, and mitochondrial ABC transporters; (b) spliceosome proteins that regulate mRNA alternative splicing machinery, and (c) proteins involved in translation within mitochondria. Our findings suggest that alternative splicing and mechanisms that modulate mitochondrial protein synthesis are central features of the molecular mechanisms aimed at maintaining mitochondrial function in the face of impairment. Whether these mechanisms are compensatory attempt to counteract the effect of aging on mitochondrial function should be further tested in longitudinal studies.
Articles you may be interested inHigh temperature spin dynamics in linear magnetic chains, molecular rings, and segments by nuclear magnetic resonance We present the room temperature proton nuclear magnetic resonance (NMR) nuclear spin-lattice relaxation rate (NSLR) results in two 1D spin chains: the Heisenberg antiferromagnetic (AFM) Eu(hfac) 3 NITEt and the magnetically frustrated Gd(hfac) 3 NITEt. The NSLR as a function of external magnetic field can be interpreted very well in terms of high temperature spin dynamics dominated by a long time persistence of the decay of the two-spin correlation function due to the conservation of the total spin value for isotropic Heisenberg chains. The high temperature spin dynamics are also investigated in Heisenberg AFM molecular rings. In both Cr 8 closed ring and in Cr 7 Cd and Cr 8 Zn open rings, i.e., model systems for a finite spin segment, an enhancement of the low frequency spectral density is found consistent with spin diffusion but the high cut-off frequency due to intermolecular anisotropic interactions prevents a detailed analysis of the spin diffusion regime. V C 2015 AIP Publishing LLC.[http://dx
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