Summary This 3-year longitudinal study among older adults showed that declining muscle mass, strength, power, and physical performance are independent contributing factors to increased fear of falling, while declines of muscle mass and physical performance contribute to deterioration of quality of life. Our findings reinforce the importance of preserving muscle health with advancing age. Introduction The age-associated loss of skeletal muscle quantity and function are critical determinants of independent physical functioning in later life. Longitudinal studies investigating how decrements in muscle components of sarcopenia impact fear of falling (FoF) and quality of life (QoL) in older adults are lacking. Methods Twenty-six healthy older subjects (age, 74.1±3.7; Short Physical Performance Battery (SPPB) score ≥10) and 22 mobility-limited older subjects (age, 77.2±4.4; SPPB score ≥9) underwent evaluations of lower extremity muscle size and composition by computed tomography, strength and power, and physical performance at baseline and after 3-year follow-up. The Falls Efficacy Scale (FES) and Short Form-36 questionnaire (SF-36) were also administered at both timepoints to assess FoF and QoL, respectively. Results At 3-year follow-up, muscle cross-sectional area (CSA) (p<0.013) and power decreased (p<0.001), while intermuscular fat infiltration increased (p<0.001). These decrements were accompanied with a longer time to complete 400 m by 22±46 s (p<0.002). Using linear mixed-effects regression models, declines of muscle CSA, strength and power, and SPPB score were associated with increased FES score (p<0.05 for each model). Reduced physical component summary score of SF-36 over follow-up was independently associated with decreased SPPB score (p<0.020), muscle CSA (p<0.046), and increased 400 m walk time (p<0.003). Conclusions In older adults with and without mobility limitations, declining muscle mass, strength, power, and physical performance contribute independently to increase FoF, while declines of muscle mass and physical performance contribute to deterioration of QoL. These findings provide further rationale for developing interventions to improve aging muscle health.

Purpose This longitudinal study examined the major physiological mechanisms that determine the age-related loss of lower extremity muscle power in two distinct groups of older humans. We hypothesized that after ~ 3 years of follow-up, mobility-limited older adults (mean age: 77.2 ± 4, n = 22, 12 females) would have significantly greater reductions in leg extensor muscle power compared to healthy older adults (74.1 ± 4, n = 26, 12 females). Methods Mid-thigh muscle size and composition were assessed using computed tomography. Neuromuscular activation was quantified using surface electromyography and vastus lateralis single muscle fibers were studied to evaluate intrinsic muscle contractile properties. Results At follow-up, the overall magnitude of muscle power loss was similar between groups: mobility-limited: −8.5% vs. healthy older: −8.8%, P > 0.8. Mobility-limited elders had significant reductions in muscle size (−3.8%, P< 0.01) and strength (−5.9%, P< 0.02), however, these parameters were preserved in healthy older (P ≥ 0.7). Neuromuscular activation declined significantly within healthy older but not in mobility-limited participants. Within both groups, the cross sectional areas of type I and type IIA muscle fibers were preserved while substantial increases in single fiber peak force ( > 30%), peak power (> 200%) and unloaded shortening velocity (>50%) were elicited at follow-up. Conclusion Different physiological mechanisms contribute to the loss of lower extremity muscle power in healthy older and mobility-limited older adults. Neuromuscular changes may be the critical early determinant of muscle power deficits with aging. In response to major whole muscle decrements, major compensatory mechanisms occur within the contractile properties of surviving single muscle fibers in an attempt to restore overall muscle power and function with advancing age.

clinicaltrials.gov NCT01836380.

One of the most fundamental adaptive physiological events is the response of skeletal muscle to high-intensity resistance exercise, resulting in increased protein synthesis and ultimately larger muscle mass. However, muscle growth in response to contraction is attenuated in older humans. Impaired contractile-induced muscle growth may contribute to sarcopenia: the age-associated loss of muscle mass and function that is manifested by loss of strength, contractile capacity, and endurance. We hypothesized that the storage of ceramide would be increased in older individuals and this would be associated with increases in NFκB signaling and a decreased anabolic response to exercise. To test this hypothesis we measured ceramides at rest and anabolic and NFκB signaling after an acute bout of high-intensity resistance exercise in young and older males. Using lipidomics analysis we show there was a 156% increase in the accumulation of C16:0-ceramide (P < 0.05) and a 30% increase in C20:0-ceramide (P < 0.05) in skeletal muscle with aging, although there was no observable difference in total ceramide. C16:0-ceramide content was negatively correlated (P = 0.008) with lower leg lean mass. Aging was associated with a ~60% increase in the phosphorylation of the proinflammatory transcription factor NFκB in the total and nuclear cell fractions (P < 0.05). Furthermore, there was an attenuated activation of anabolic signaling molecules such as Akt (P < 0.05), FOXO1 (P < 0.05), and S6K1 (P < 0.05) after an acute bout of high-intensity resistance exercise in older males. We conclude that ceramide may have a significant role in the attenuation of contractile-induced skeletal muscle adaptations and atrophy that is observed with aging.

Background: Central arterial stiffness and brain hypoperfusion are emerging risk factors of Alzheimer’s disease (AD). Aerobic exercise training (AET) may improve central arterial stiffness and brain perfusion. Objective: To investigate the effects of AET on central arterial stiffness and cerebral blood flow (CBF) in patients with amnestic mild cognitive impairment (MCI), a prodromal stage of AD. Methods: This is a proof-of-concept, randomized controlled trial that assigned 70 amnestic MCI patients into a 12-month program of moderate-to-vigorous AET or stretching-and-toning (SAT) intervention. Carotid β-stiffness index and CBF were measured by color-coded duplex ultrasonography and applanation tonometry. Total CBF was measured as the sum of CBF from both the internal carotid and vertebral arteries, and divided by total brain tissue mass assessed with MRI to obtain normalized CBF (nCBF). Episodic memory and executive function were assessed using standard neuropsychological tests (CVLT-II and D-KEFS). Changes in cardiorespiratory fitness were measured by peak oxygen uptake (VO2peak). Results: Total 48 patients (29 in SAT and 19 in AET) were completed one-year training. AET improved VO2peak, decreased carotid β-stiffness index and CBF pulsatility, and increased nCBF. Changes in VO2peak were associated positively with changes in nCBF (r = 0.388, p = 0.034) and negatively with carotid β-stiffness index (r = –0.418, p = 0.007) and CBF pulsatility (r = –0.400, p = 0.014). Decreases in carotid β-stiffness were associated with increases in cerebral perfusion (r = –0.494, p = 0.003). AET effects on cognitive performance were minimal compared with SAT. Conclusion: AET reduced central arterial stiffness and increased CBF which may precede its effects on neurocognitive function in patients with MCI.

No abstract

The aging US population and the recent rise in the prevalence of obesity are two phenomena of great importance to public health. In addition, research suggests that midlife body mass index (BMI) is a risk factor for dementia, a particularly costly disease, in later life. BMI could influence brain health by adversely impacting cerebral white matter. Recently, greater BMI has been associated with lower white matter fractional anisotropy (FA), an index of tissue microstructure, as measured by diffusion-tensor imaging (DTI) in midlife. The aim of this study was to investigate the role of abdominal obesity, the most metabolically active adipose tissue compartment, and white matter microstructure in midlife. Community dwelling participants (N=168) between the ages of 40 – 62 underwent MRI scanning at 3T and a general health assessment. Inferences were made on whole brain white matter tracts using full-tensor, high-dimension normalization and tract based spatial statistics. Higher waist circumference was associated with higher FA, indicating more directional diffusion in several white matter tracts controlling for age, sex, triglycerides, systolic blood pressure, fasting glucose, and HDL-cholesterol. Post-hoc analysis reveled that greater waist circumference was associated with lower axial diffusivity (AD), indicating lower parallel diffusion; lower radial diffusivity (RD), indicating lower perpendicular diffusion; and lower mean diffusivity (MD), indicating restricted diffusion. This is the first study to report a positive relationship between obesity and FA, indicating a more complicated view of this relationship in the aging brain.

The present findings suggest that voluntary neuromuscular activation declines with advancing age, contributes to a reduction in power production, and precedes the decline of mobility function.