Severity of polycystic kidney disease revealed by multiparametric MRI.

PURPOSE: We aimed to compare multiple MRI parameters, including relaxation rates ( R 1 $$ {R}_1 $$ , R 2 $$ {R}_2 $$ , and R 1 ρ $$ {R}_{1\rho } $$ ), ADC from diffusion weighted imaging, pool size ratio (PSR) from quantitative magnetization transfer, and measures of exchange from spin-lock imaging ( S ρ $$ {S}_{\rho } $$ ), for assessing and predicting the severity of polycystic kidney disease (PKD) over time. METHODS: Pcy/Pcy mice with CD1 strain, a mouse model of autosomal dominant PKD, were imaged at 5, 9, and 26 wk of age using a 7T MRI system. Twelve-week normal CD1 mice were used as controls. Post-mortem paraffin tissue sections were stained using hematoxylin and eosin and picrosirius red to identify histological changes. RESULTS: Histology detected segmental cyst formation in the early stage (week 5) and progression of PKD over time in Pcy kidneys. In T 2 $$ {T}_2 $$ -weighted images, small cysts appeared locally in cystic kidneys in week 5 and gradually extended to the whole cortex and outer stripe of outer medulla region from week 5 to week 26. Regional PSR, R 1 $$ {R}_1 $$ , R 2 $$ {R}_2 $$ , and R 1 ρ $$ {R}_{1\rho } $$ decreased consistently over time compared to normal kidneys, with significant changes detected in week 5. Among all the MRI measures, R 2 $$ {R}_2 $$ and R 1 ρ $$ {R}_{1\rho } $$ allow highest detectability to PKD, while PSR and R 1 $$ {R}_1 $$ have highest correlation with pathological indices of PKD. Using optimum MRI parameters as regressors, multiple linear regression provides reliable prediction of PKD progression. CONCLUSION: R 2 $$ {R}_2 $$ , R 1 $$ {R}_1 $$ , and PSR are sensitive indicators of the presence of PKD. Multiparametric MRI allows a comprehensive analysis of renal changes caused by cyst formation and expansion.

Correction of errors in estimates of T1ρ at low spin-lock amplitudes in the presence of B0 and B1 inhomogeneities.

Relaxation rates R1ρ in the rotating frame measured by spin-lock methods at very low locking amplitudes (≤ 100 Hz) are sensitive to the effects of water diffusion in intrinsic gradients and may provide information on tissue microvasculature, but accurate estimates are challenging in the presence of B0 and B1 inhomogeneities. Although composite pulse preparations have been developed to compensate for nonuniform fields, the transverse magnetization comprises different components and the spin-lock signals measured do not decay exponentially as a function of locking interval at low locking amplitudes. For example, during a typical preparation sequence, some of the magnetization in the transverse plane is nutated to the Z-axis and later tipped back, and so does not experience R1ρ relaxation. As a result, if the spin-lock signals are fit to a monoexponential decay with locking interval, there are residual errors in quantitative estimates of relaxation rates R1ρ and their dispersion with weak locking fields. We developed an approximate theoretical analysis to model the behaviors of the different components of the magnetization, which provides a means to correct these errors. The performance of this correction approach was evaluated both through numerical simulations and on human brain images at 3 T, and compared with a previous correction method using matrix multiplication. Our correction approach has better performance than the previous method at low locking amplitudes. Through careful shimming, the correction approach can be applied in studies using low spin-lock amplitudes to assess the contribution of diffusion to R1ρ dispersion and to derive estimates of microvascular sizes and spacings. The results of imaging eight healthy subjects suggest that R1ρ dispersion in human brain at low locking fields arises from diffusion among inhomogeneities that generate intrinsic gradients on a scale of capillaries (~7.4 ± 0.5 µm).

Multiparametric magnetic resonance imaging in diagnosis of long-term renal atrophy and fibrosis after ischemia reperfusion induced acute kidney injury in mice.

Tubular atrophy and fibrosis are pathological changes that determine the prognosis of kidney disease induced by acute kidney injury (AKI). We aimed to evaluate multiple magnetic resonance imaging (MRI) parameters, including pool size ratio (PSR) from quantitative magnetization transfer, relaxation rates, and measures from spin-lock imaging ( R 1 ρ and S ρ ), for assessing the pathological changes associated with AKI-induced kidney disease. Eight-week-old male C57BL/6 J mice first underwent unilateral ischemia reperfusion injury (IRI) induced by reperfusion after 45 min of ischemia. They were imaged using a 7T MRI system 56 days after the injury. Paraffin tissue sections were stained using Masson trichrome and picrosirius red to identify histopathological changes such as tubular atrophy and fibrosis. Histology detected extensive tubular atrophy and moderate fibrosis in the cortex and outer stripe of the outer medulla (CR + OSOM) and more prominent fibrosis in the inner stripe of the outer medulla (ISOM) of IRI kidneys. In the CR + OSOM region, evident decreases in PSR, R 1 , R 2 , R 1 ρ , and S ρ showed in IRI compared with contralateral kidneys, with PSR and S ρ exhibiting the most significant changes. In addition, the exchange parameter S ρ dropped by the largest degree among all the MRI parameters, while R 2 * increased significantly. In the ISOM of IRI kidneys, PSR increased while S ρ kept decreasing. R 2 , R 1 ρ , and R 2 * all increased due to more severe fibrosis in this region. Among MRI measures, PSR and R 1 ρ showed the highest detectability of renal changes no matter whether tubular atrophy or fibrosis dominated. R 2 * and S ρ could be more specific to a single pathological event than other MRI measures because only R 2 * increased and S ρ decreased consistently when either fibrosis or tubular atrophy dominated, and their correlations with fibrosis scores were higher than other MRI measures. Multiparametric MRI may enable a more comprehensive analysis of histopathological changes following AKI.

Parsimonious modeling of skeletal muscle perfusion: Connecting the stretched exponential and fractional Fickian diffusion.

PURPOSE: To develop an anomalous (non-Gaussian) diffusion model for characterizing skeletal muscle perfusion using multi-b-value DWI. THEORY AND METHODS: Fick's first law was extended for describing tissue perfusion as anomalous superdiffusion, which is non-Gaussian diffusion exhibiting greater particle spread than that of the Gaussian case. This was accomplished using a space-fractional derivative that gives rise to a power-law relationship between mean squared displacement and time, and produces a stretched exponential signal decay as a function of b-value. Numerical simulations were used to estimate parameter errors under in vivo conditions, and examine the effect of limited SNR and residual fat signal. Stretched exponential DWI parameters, α and D , were measured in thigh muscles of 4 healthy volunteers at rest and following in-magnet exercise. These parameters were related to a stable distribution of jump-length probabilities and used to estimate microvascular volume fractions. RESULTS: Numerical simulations showed low dispersion in parameter estimates within 1.5% and 1%, and bias errors within 3% and 10%, for α and D , respectively. Superdiffusion was observed in resting muscle, and to a greater degree following exercise. Resting microvascular volume fraction was between 0.0067 and 0.0139 and increased between 2.2-fold and 4.7-fold following exercise. CONCLUSIONS: This model captures superdiffusive molecular motions consistent with perfusion, using a parsimonious representation of the DWI signal, providing approximations of microvascular volume fraction comparable with histological estimates. This signal model demonstrates low parameter-estimation errors, and therefore holds potential for a wide range of applications in skeletal muscle and elsewhere in the body.

Diffusion-weighted MRI with intravoxel incoherent motion modeling for assessment of muscle perfusion in the thigh during post-exercise hyperemia in younger and older adults.

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 (fp ) 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 fp and D ranged from 3.2% to 9.5% and from 0.9% to 1.1%, respectively. The mid-thigh 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 fp 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.

Low temperature magnetic properties and spin dynamics in single crystals of Cr8Zn antiferromagnetic molecular rings.

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 Cr8Zn. 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 µ0Hc1 = 2.15 T is found to be an almost true LC while the second LC at µ0Hc2 = 6.95 T has an anti-crossing gap of Δ12 = 0.19 K. In addition, both NMR and specific heat measurements show the presence of a level anti-crossing between excited states at µ0H = 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 âˆ¼ 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.

R1ρ dispersion in white matter correlates with quantitative metrics of cognitive impairment.

Much previous neuroimaging research in Alzheimer's disease has focused on the roles of amyloid and tau proteins, but recent studies have implicated microvascular changes in white matter as early indicators of damage related to later dementia. We used MRI to derive novel, non-invasive measurements of R1ρ dispersion using different locking fields to characterize variations of microvascular structure and integrity in brain tissues. We developed a non-invasive 3D R1ρ dispersion imaging technique using different locking fields at 3T. We acquired MR images and cognitive assessments of participants with mild cognitive impairment (MCI) and compared them to age-matched healthy controls in a cross-sectional study. After providing informed consent, 40 adults aged 62 to 82 years (n = 17 MCI) were included in this study. White matter ΔR1ρ-fraction measured by R1ρ dispersion imaging showed a strong correlation with the cognitive status of older adults (ßstd = -0.4, p-value < 0.01) independent of age, in contrast to other conventional MRI markers such as T2, R1ρ, and white matter hyperintense lesion volume (WMHs) measured with T2-FLAIR. The correlation of WMHs with cognitive status was no longer significant after adjusting for age and sex in linear regression analysis, and the size of the regression coefficient was substantially decreased (53% lower). This work establishes a new non-invasive method that potentially characterizes impairment of the microvascular structure of white matter in MCI patients compared to healthy controls. The application of this method in longitudinal studies would improve our fundamental understanding of the pathophysiologic changes that accompany abnormal cognitive decline with aging and help identify potential targets for treatment of Alzheimer's disease.

Age-related changes in human skeletal muscle microstructure and architecture assessed by diffusion-tensor magnetic resonance imaging and their association with muscle strength.

Diffusion-tensor magnetic resonance imaging (DT-MRI) offers objective measures of muscle characteristics, providing insights into age-related changes. We used DT-MRI to probe skeletal muscle microstructure and architecture in a large healthy-aging cohort, with the aim of characterizing age-related differences and comparing these to muscle strength. We recruited 94 participants (43 female; median age = 56, range = 22-89 years) and measured microstructure parameters-fractional anisotropy (FA) and mean diffusivity (MD)-in 12 thigh muscles, and architecture parameters-pennation angle, fascicle length, fiber curvature, and physiological cross-sectional area (PCSA)-in the rectus femoris (RF) and biceps femoris longus (BFL). Knee extension and flexion torques were also measured for comparison to architecture measures. FA and MD were associated with age (ß = 0.33, p = 0.001, R2 = 0.10; and ß = -0.36, p < 0.001, R2 = 0.12), and FA was negatively associated with Type I fiber proportions from the literature (ß = -0.70, p = 0.024, and R2 = 0.43). Pennation angle, fiber curvature, fascicle length, and PCSA were associated with age in the RF (ß = -0.22, 0.26, -0.23, and -0.31, respectively; p < 0.05), while in the BFL only curvature and fascicle length were associated with age (ß = 0.36, and -0.40, respectively; p < 0.001). In the RF, pennation angle and PCSA were associated with strength (ß = 0.29, and 0.46, respectively; p < 0.01); in the BFL, only PCSA was associated with strength (ß = 0.43; p < 0.001). Our results show skeletal muscle architectural changes with aging and intermuscular differences in the microstructure. DT-MRI may prove useful for elucidating muscle changes in the early stages of sarcopenia and monitoring interventions aimed at preventing age-associated microstructural changes in muscle that lead to functional impairment.

Ankle-Brachial Index and Energy Production in People Without Peripheral Artery Disease: The BLSA.

Background Lower ankle-brachial index (ABI) values within the 0.90 to 1.40 range are associated with poorer mitochondrial oxidative capacity of thigh muscles in cross-sectional analyses. Whether ABI decline is associated with greater declines in thigh muscle oxidative capacity with aging is unknown. Method and Results We analyzed data from 228 participants (100 men) of the BLSA (Baltimore Longitudinal Study of Aging), aged 39 to 97 years, with an ABI between 0.9 and 1.40 at baseline and at follow-up (mean follow-up period of 2.8 years). We examined mitochondrial oxidative capacity of the left thigh muscle, by measuring the postexercise phosphocreatine recovery rate constant (kPCr) from phosphorus-31 magnetic resonance spectroscopy. Greater kPCr indicated higher mitochondrial oxidative capacity. Although kPCr was available on the left leg only, ABI was measured in both legs. Longitudinal rates of change (Change) of left and right ABI and kPCr of the left thigh muscle were estimated using linear mixed effects models, and their association was analyzed by standardized multiple linear regressions. In multivariate analysis including sex, age, baseline kPCr, both left and right baseline ABI, and ABI change in both legs, (kPCr)Change was directly associated with ipsilateral (left) (ABI)Change (standardized [STD]-ß=0.14; P=0.0168) but not with contralateral (right) (ABI)Change (P=0.22). Adjusting for traditional cardiovascular risk factors, this association remained significant (STD-ß=0.18; P=0.0051). (kPCr)Change was steeper in White race participants (STD-ß=0.16; P=0.0122) and body mass index (STD-ß=0.13; P=0.0479). There was no significant association with current smoking status (P=0.63), fasting glucose (P=0.28), heart rate (P=0.67), mean blood pressure (P=0.78), and low-density lipoprotein (P=0.75), high-density lipoprotein (P=0.82), or triglycerides (P=0.15). Conclusions In people without peripheral arterial disease, greater decline in ABI over time, but not baseline ABI, was associated with faster decline in thigh mitochondrial oxidative capacity in the ipsilateral leg. Further studies are needed to examine whether early interventions that improve lower extremity muscle perfusion can improve and prevent the decline of muscle energetics.

Tissue characterization using R1rho dispersion imaging at low locking fields.

Measurements of the variations of spin-locking relaxation rates (R1ρ) with locking field amplitude allow the derivation of quantitative parameters that describe different dynamic processes, such as slow molecular motions, chemical exchange and diffusion. In some samples, changes in R1ρ values between locking frequency 0 and 200 Hz may be dominated mainly by diffusion of water in intrinsic field gradients, while those at higher locking fields are due to exchange processes. The exchange and diffusion effects act independently of each other, as confirmed by simulation and experimentally. In tissues, the relevant intrinsic field gradients may arise from the magnetic inhomogeneities caused by microvascular blood so that R1ρ dispersion over weak locking field amplitudes (≤ 200 Hz) is affected by changes in capillary density and geometry. Here we first review the theoretical and experimental background to the interpretation of R1ρ dispersions caused by intrinsic magnetic susceptibility variations within the tissue. We then provide new empirical results of R1ρ dispersion imaging of the human brain and skeletal muscle at low locking field amplitudes for the first time and identify potential applications of R1ρ dispersion imaging in clinical studies.

Greater Skeletal Muscle Oxidative Capacity Is Associated With Higher Resting Metabolic Rate: Results From the Baltimore Longitudinal Study of Aging.

Resting metabolic rate (RMR) tends to decline with aging. The age-trajectory of decline in RMR is similar to changes that occur in muscle mass, muscle strength, and fitness, but while the decline in these phenotypes has been related to changes of mitochondrial function and oxidative capacity, whether lower RMR is associated with poorer mitochondrial oxidative capacity is unknown. In 619 participants of the Baltimore Longitudinal Study of Aging, we analyzed the cross-sectional association between RMR (kcal/day), assessed by indirect calorimetry, and skeletal muscle maximal oxidative phosphorylation capacity, assessed as postexercise phosphocreatine recovery time constant (τ PCr), by phosphorous magnetic resonance spectroscopy. Linear regression models were used to evaluate the relationship between τ PCr and RMR, adjusting for potential confounders. Independent of age, sex, lean body mass, muscle density, and fat mass, higher RMR was significantly associated with shorter τ PCr, indicating greater mitochondrial oxidative capacity. Higher RMR is associated with a higher mitochondrial oxidative capacity in skeletal muscle. This association may reflect a relationship between better muscle quality and greater mitochondrial health.

Proteomic signatures of in vivo muscle oxidative capacity in healthy adults.

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 31 P 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.

The Role of Muscle Perfusion in the Age-Associated Decline of Mitochondrial Function in Healthy Individuals.

Maximum oxidative capacity of skeletal muscle measured by in vivo phosphorus magnetic resonance spectroscopy (31P-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 31P-MRS post-exercise phosphocreatine recovery time (τPCr), with higher τPCr 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-VO2) was also measured during a graded treadmill exercise test in the same visit. Muscle oxidative capacity, peak-VO2, and resting muscle perfusion were significantly lower at older ages independent of sex, race, and body mass index (BMI). τPCr was significantly associated with resting muscle perfusion independent of age, sex, race, and BMI (p-value = 0.004, ß = -0.34). τPCr was also a significant independent predictor of peak-VO2 and, in a mediation analysis, significantly attenuated the association between muscle perfusion and peak-VO2 (34% reduction for ß 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.

Age and Muscle Function Are More Closely Associated With Intracellular Magnesium, as Assessed by 31P Magnetic Resonance Spectroscopy, Than With Serum Magnesium.

Total serum magnesium is a common clinical measurement for assessing magnesium status; however, magnesium in blood represents less than 1% of the body's total magnesium content. We measured intramuscular ionized magnesium by phosphorus magnetic resonance spectroscopy (31P-MRS) and tested the hypothesis that this measure better correlates with skeletal muscle function and captures more closely the effect of aging than the traditional measure of total serum magnesium. Data were collected from 441 participants (age 24-98 years) in the Baltimore Longitudinal Study of Aging (BLSA), a study of normative aging that encompasses a broad age range. Results showed that intramuscular ionized magnesium was negatively associated with age (ß = -0.29, p < 0.001, R 2 = 0.08) and positively associated with knee-extension strength (ß = 0.31, p < 0.001, and R 2 = 0.1 in women; and ß = 0.2, p = 0.003, and R 2 = 0.04 in men), while total serum magnesium showed no association with age or strength (p = 0.27 and 0.1, respectively). Intramuscular ionized magnesium was significantly lower in women that in men (p < 0.001), perhaps due to chronic latent Mg deficiency in women that is not otherwise detected by serum magnesium levels. Based on these findings, we suggest that intramuscular ionized magnesium from 31P-MRS is a better clinical measure of magnesium status than total serum magnesium, and could be measured when muscle weakness of unidentified etiology is detected. It may also be used to monitor the effectiveness of oral magnesium interventions, including supplementation.

Moderate-to-Vigorous Physical Activity Is Associated With Higher Muscle Oxidative Capacity in Older Adults.

BACKGROUND: Age-related decline in muscle oxidative capacity reduces muscle function and physical performance, leading to disability and frailty. Whether age-related decline in oxidative capacity is modified by exercise and other lifestyle practices is unclear. Therefore, we tested the hypothesis that physical activity is associated with better oxidative capacity, independent of age. DESIGN: Cross-sectional study performed in the Baltimore Longitudinal Study of Aging, conducted by the Intramural Research Program (IRP) of the National Institute on Aging (NIA). SETTING: NIA IRP Clinical Research Unit, Baltimore, MD. PARTICIPANTS: Participants included 384 adults (54.7% women), aged 22 to 92 years, seen between 2013 and 2017. MEASUREMENTS: Muscle oxidative capacity was measured in vivo using phosphorous magnetic resonance spectroscopy. We determined the postexercise time constant (τPCr ; in seconds) for phosphocreatine (PCr) recovery, with lower values of τPCr, (ie, more rapid recovery of PCr levels after exercise) reflecting greater oxidative capacity. Time spent in moderate-to-vigorous physical activity (MVPA) was assessed using wearable accelerometers that participants wore 5.9 ± 0.9 consecutive days in the free-living environment. RESULTS: In linear regression models, higher τPCr was associated with older age (standardized ß = .39; P < .001) after adjusting for sex, race, height, and weight. After including MVPA as an independent variable, the standardized regression coefficient of age decreased by 40%, but remained associated with τPCr (ßage = .22; P < .001) and had a smaller standardized regression coefficient than MVPA (ßMVPA = -.33; P < .001). After adjusting for health status, education, and smoking history, the standardized regression coefficient for age decreased 12% (ßage = .20; P = .003), while the standardized coefficient for MVPA decreased only 3% (ßMVPA = -.32; P < .001). CONCLUSION: Study findings suggest that MVPA is strongly associated with muscle oxidative capacity, independent of age, providing mechanistic insights into the health benefits of exercise in older age. J Am Geriatr Soc 67:1695-1699, 2019.

Low plasma lysophosphatidylcholines are associated with impaired mitochondrial oxidative capacity in adults in the Baltimore Longitudinal Study of Aging.

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 (31 P-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.

Searching for a mitochondrial root to the decline in muscle function with ageing.

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.

Comparison of spin dynamics and magnetic properties in antiferromagnetic closed and open molecular Cr-based rings.

We present magnetization and (1)H nuclear magnetic resonance (NMR) measurements performed in both closed Cr8 and open Cr8Zn antiferromagnetic molecular rings in the temperature range 1.65 < T < 300 K at different external magnetic fields. The magnetization measurements on Cr8Zn are consistent with a small decrease of the exchange constant J(Cr-Cr) and a much smaller gap between the singlet ground state and the first magnetic excited state when compared with the same properties of the closed ring Cr8, in agreement with previous inelastic neutron scattering results. The temperature dependence of the (1)H NMR nuclear spin lattice relaxation rate (NSLR), 1/T1(T), was found to be similar in both open and closed rings with a magnetic field dependent peak centered at a temperature of the order of the corresponding exchange constant J(Cr-Cr). Such main peak in the NSLR could be fitted with a single correlation frequency ω(c1) as in most molecular magnets. At low temperature T < 4 K, a new feature not observed in previous NMR measurements on antiferromagnetic rings and consisting in a smaller peak of 1/T1(T) which is well resolved only in Cr8Zn, was singled out. This low-T peak indicates the presence of a second correlation frequency ω(c2) of the magnetization, found to be quite different between the two rings and thus possibly reflecting the different low temperature level structure associated with the different spin topology. The presence of ω(c2) is confirmed by the NMR spin-spin relaxation rate enhancement, which generates a two-steps wipe-out effect of the NMR signal intensity.