Influence of aging on the in vivo properties of human patellar tendon

Tendons are important for optimal muscle force transfer to bone and play a key role in functional ability. Changes in tendon properties with aging could contribute to declines in physical function commonly associated with aging. We investigated the in vivo mechanical properties of the patellar tendon in 37 men and women [11 young (27 +/- 1 yr) and 26 old (65 +/- 1 yr)] using ultrasonography and magnetic resonance imaging (MRI). Patella displacement relative to the tibia was monitored with ultrasonography during ramped isometric contractions of the knee extensors, and MRI was used to determine tendon cross-sectional area (CSA) and signal intensity. At peak force, patellar tendon deformation, stress, and strain were 13 (P = 0.05), 19, and 12% less in old compared with young (P < 0.05). Additionally, deformation, stiffness, stress, CSA, and length were 18, 35, 41, 28, and 11% greater (P < 0.05), respectively, in men compared with women. After normalization of mechanical properties to a common force, no age differences were apparent; however, stress and strain were 26 and 22% higher, respectively, in women compared with men (P < 0.05). CSA and signal intensity decreased 12 and 24%, respectively, with aging (P < 0.05) in the midregion of the tendon. These data suggest that differences in patellar tendon in vivo mechanical properties with aging are more related to force output rather than an age effect. In contrast, the decrease in signal intensity indirectly suggests that the internal milieu of the tendon is altered with aging; however, the physiological and functional consequence of this finding requires further study.     

Modulation of motor unit firing rates during a complex sinusoidal force task in young and older adults.

This study compared motor unit rate coding and muscular force control in the first dorsal interosseous muscle of older (n = 11, mean 72.3 yr) and young (n = 12, mean 18.7 yr) adults. Rate coding during a sinusoidal isometric force-matching task was evaluated using spectral analysis of the time-varying changes in firing rate. The task required force modulations to match a trajectory comprising the sum of 0.15- and 0.45-Hz sine waves. Based on the amplitude of spectral peaks at 0.15 and 0.45 Hz, the amplitude of force modulation was similar in young and older adults at both frequencies (F = 1.9, P = 0.17). Force modulation gain (FMG) was computed as the ratio of the amplitude of force modulation to the amplitude of firing rate modulation. To account for rate coding differences related to the properties of the motoneuron, recruitment threshold force was used as a covariate in age-group comparisons. At both task frequencies, firing rate was modulated with less amplitude (F = 0 14, P < 0.001) and FMG was greater (F = 0 27, P < 0.001) in the older adults. In its transformation of neural input to mechanical output, muscle is known to act as a low-pass filter. Compared with modulation at 0.15 Hz, less change in force per change in firing rate at 0.45 Hz (lower FMG; F = 0 67, P < 0.001), independent of age group, is consistent with this filtering effect. Our conclusion is that there is a reduced amplitude of firing rate modulation in older adults.     

Handling objects in old age: forces and moments acting on the object

We measured the external moments and digit-tip force directions acting on a freely moveable object while it was grasped and manipulated by old (OA) and young (YA) adults. Participants performed a grasp and lift task and a precision orientation (key-slot) task with a precision (thumb-finger) grip. During the grasp-lift task the OA group misaligned their thumb and finger contacts and produced greater grip force, greater external moments on the object around its roll axis, and oriented force vectors differently compared with the YA group. During the key-slot task, the OA group was more variable in digit-tip force directions and performed the key-slot task more slowly. With practice the OA group aligned their digits, reduced their grip force, and minimized external moments on the object, clearly demonstrating that the nervous system monitored and actively manipulated one or more variables related to object tilt. This was true even for the grip-lift task, a task for which no instructions regarding object orientation were given and which could tolerate modest amounts of object tilt without interfering with task goals. Although the OA group performed the key-slot task faster with experience, they remained slower than the YA group. We conclude that with old age comes a reduced ability to control the forces and moments applied to objects during precision grasp and manipulation. This may contribute to the ubiquitous slowing and deteriorating manual dexterity in healthy aging.     

Collagen, cross-linking, and advanced glycation end products in aging human skeletal muscle.

We examined intramuscular endomysial collagen, cross-linking, and advanced glycation end products, as well as the general and contractile protein concentration of 20 young (25 +/- 3 yr) and 22 old (78 +/- 6 yr, range: 70-93 yr) sedentary men and women to better understand the underlying basis of changes in skeletal muscle mass and function that occur with aging. The old individuals had an impaired ability (increased time) (P < 0.05) to climb stairs (80%), rise from a chair (56%), and walk (44%), as well as lower (P < 0.05) quadriceps muscle volume (-29%), muscle strength (-35%), muscle power (-48%), and strength (-17%) and power (-33%) normalized to muscle size. Vastus lateralis muscle biopsies revealed that intramuscular endomysial collagen (young: 9.6 +/- 1.1, old: 10.2 +/- 1.2 microg/mg muscle wet wt) and collagen cross-linking (hydroxylysylpyridinoline) (young: 395 +/- 65, old: 351 +/- 45 mmol hydroxylysylpyridinoline/mol collagen) were unchanged (P > 0.05) with aging. The advanced glycation end product, pentosidine, was increased (P < 0.05) by approximately 200% (young: 5.2 +/- 1.3, old: 15.9 +/- 4.5 mmol pentosidine/mol collagen) with aging. While myofibrillar protein concentration was lower (-5%, P < 0.05), the concentration of the main contractile proteins myosin and actin were unchanged (P > 0.05) with aging. These data suggest that the synthesis and degradation of proteins responsible for the generation (myosin and actin) and transfer (collagen and pyridinoline cross-links) of muscle force are tightly regulated in aging muscle. Glycation-related cross-linking of intramuscular connective tissue may contribute to altered muscle force transmission and muscle function with healthy aging.     

Time to task failure and muscle activation vary with load type for a submaximal fatiguing contraction with the lower leg.

The purpose was to compare the time to failure and muscle activation patterns for a sustained isometric submaximal contraction with the dorsiflexor muscles when the foot was restrained to a force transducer (force task) compared with supporting an equivalent inertial load and unrestrained (position task). Fifteen men and women (mean+/-SD; 21.1+/-1.4 yr) performed the force and position tasks at 20% maximal voluntary contraction force until task failure. Maximal voluntary contraction force performed before the force and position tasks was similar (333+/-71 vs. 334+/-65 N), but the time to task failure was briefer for the position task (10.0+/-6.2 vs. 21.3+/-17.8 min, P<0.05). The rate of increase in agonist root-mean-square electromyogram (EMG), EMG bursting activity, rating of perceived exertion, fluctuations in motor output, mean arterial pressure, and heart rate during the fatiguing contraction was greater for the position task. EMG activity of the vastus lateralis (lower leg stabilizer) and medial gastrocnemius (antagonist) increased more rapidly during the position task, but coactivation ratios (agonist vs. antagonist) were similar during the two tasks. Thus the difference in time to failure for the two tasks with the dorsiflexor muscles involved a greater level of neural activity and rate of motor unit recruitment during the position task, but did not involve a difference in coactivation. These findings have implications for rehabilitation and ergonomics in minimizing fatigue during prolonged activation of the dorsiflexor muscles.     

Age and contraction type influence motor output variability in rapid discrete tasks.

The purpose of this study was to examine the ability to control knee-extension force during discrete isometric (IC), concentric (CC), and eccentric contractions (EC) in 24 young (mean age +/- SD = 25.3 +/- 2.8 yr) and 24 old (mean age +/- SD = 73.3 +/- 5.5 yr) healthy and active individuals. Subjects were to match a parabola with a time to peak force of 200 ms during IC, CC, and EC at six target levels of force [20, 35, 50, 65, 80, and 90% of the maximum voluntary contraction (MVC)]. ICs were performed at 90 degrees of knee flexion, whereas CCs and ECs ranged from 90 to 80 degrees of knee flexion (0 degrees is full extension) at a slow velocity (25 degrees /s). Results showed that subjects produced similar MVC forces for the three types of contractions. Young subjects produced greater MVC forces than old subjects, and within each age group, men produced greater force than women. The variability (standard deviation) of peak force and impulse in absolute values was greater for young compared with old subjects. When variability was normalized to the force produced [coefficient of variation (CV)], however, old subjects exhibited greater CV than young subjects for peak force and impulse. Both the standard deviation and CV of time to peak force and impulse duration were greater for the old adults. In general, ECs were more variable than ICs and CCs, and old adults exhibited greater CV compared with young adults during rapid, discrete ICs, CCs, and particularly ECs of the quadriceps.     

Sexual dimorphism in the complexity of cardiac pacemaker activity

This study explored the effects of gender and aging on the complexity of cardiac pacemaker activity. Electrocardiogram signals were studied in normal women (n = 240) and men (n = 240) ranging in age from 40 to 79 yr. Nonlinear analysis of short-term resting R-R intervals was performed using the correlation dimension (CD), approximate entropy (ApEn), and largest Lyapunov exponent (LLE). Evidence of nonlinear structure was obtained by the surrogate data test. CD, ApEn, and LLE were negatively correlated with age. Despite similar means and SDs of the R-R intervals, women had a significantly higher CD, ApEn, and LLE compared with men in the age strata of 40-44 and 45-49 yr. CD and ApEn were strongly (r > 0.71) correlated with low- and high-frequency components. We conclude that the resting cardiac pacemaker activity of women is more complex than that of men in middle age, and the gender-related difference diminishes after the age of 50 yr. The higher complexity implies a more comprehensive neural modulation.     

Multilevel model estimation of age-dependent individual-specific trajectories for left ventricular echocardiographic indexes in an asymptomatic elderly cohort

Few studies have been performed on the individual-specific trajectory of left ventricular aging as assessed by echocardiography in an asymptomatic elderly cohort. In the present study, a representative cohort of elderly men, who were long-term asymptomatic for cardiovascular issues, were selected from an ongoing observational aging study. Annual echocardiographic data were used to establish an age-dependent hierarchical model. Based on two-level linear regression results, four echocardiographic indexes [left ventricular mass (LVmass; -1.872 g/yr), posterior ventricular wall thickness (-0.048 mm/yr), fraction shortening (0.097/yr), and transmitral peak A velocity (-0.006 m·s(-1)·yr(-1))] changed significantly with increasing age and were age- and subject-dependent. The most characterized results of the study were the significant, age-related, within-individual variances in echocardiographic results, which were observed using the likelihood ratio test at an occasion-dependent level. Of these, fluctuated amplitudes of two systolic variables [i.e., LVmass (con/age = -0.012 ± 0.004; P = 0.0007) and fraction shortening (con/age = -0.001 ± 0.004; P = 0.05)] were significantly attenuated with increasing age within individuals. On the other hand, the age-related variability of four diastolic Doppler variables [i.e., peak A velocity (con/age = 0.003 ± 0.002; P = 0.0009), peak E velocity (con/age = 0.004 ± 0.003; P = 0.01), E/A ratio (con/age = 0.007 ± 0.003; P = 0.0002), and deceleration time of E wave (con/age = 0.025 ± 0.007; P < 0.0001)] significantly increased with increasing age within individuals. The age-related individual variability of left ventricular indexes observed in this continuous asymptomatic cohort may reflect the mechanism of preclinical, individualized heart aging. In conclusion, successfully fitted multilevel models were applied as a valuable tool to determine the mechanism of individual cardiac aging in the elderly.     

Corticomuscular coherence with and without additional task in the elderly

Aging and dual-task paradigms often degrade fine motor performance, but the effects of aging on correlated neural activity between motor cortex and contracting muscle are unknown during dual tasks requiring fine motor performance. The purpose of this study was to compare corticomuscular coherence between young and elderly adults during the performance of a unilateral fine motor task and concurrent motor and cognitive tasks. Twenty-nine healthy young (18-38 yr) and elderly (61-75 yr) adults performed unilateral motor, bilateral motor, concurrent motor-cognitive, and cognitive tasks. Peak corticomuscular coherence between the electroencephalogram from the primary motor cortex and surface electromyogram from the first dorsal interosseous muscle was compared during steady abduction of the index finger with visual feedback. In the alpha-band (8-14 Hz), corticomuscular coherence was greater in elderly than young adults especially during the motor-cognitive task. The beta-band (15-32 Hz) corticomuscular coherence was higher in elderly than young adults across unilateral motor and dual tasks. In addition, beta-band corticomuscular coherence in the motor-cognitive task was negatively correlated with motor output error across young but not elderly adults. The results suggest that 1) corticomuscular coherence was increased in senior age with a greater influence of an additional cognitive task in the alpha-band and 2) individuals with greater beta-band corticomuscular coherence may exhibit more accurate motor output in young, but not elderly adults, during steady contraction with visual feedback.     

Aerobic exercise training reduces plasma endothelin-1 concentration in older women.

Endothelial function deteriorates with aging. On the other hand, exercise training improves the function of vascular endothelial cells. Endothelin-1 (ET-1), which is produced by vascular endothelial cells, has potent constrictor and proliferative activity in vascular smooth muscle cells and, therefore, has been implicated in regulation of vascular tonus and progression of atherosclerosis. We previously reported significantly higher plasma ET-1 concentration in middle-aged than in young humans, and recently we showed that plasma ET-1 concentration was significantly decreased by aerobic exercise training in healthy young humans. We hypothesized that plasma ET-1 concentration increases with age, even in healthy adults, and that lifestyle modification (i.e., exercise) can reduce plasma ET-1 concentration in previously sedentary older adults. We measured plasma ET-1 concentration in healthy young women (21-28 yr old), healthy middle-aged women (31-47 yr old), and healthy older women (61-69 yr old). The plasma level of ET-1 significantly increased with aging (1.02 +/- 0.08, 1.33 +/- 0.11, and 2.90 +/- 0.20 pg/ml in young, middle-aged, and older women, respectively). Thus plasma ET-1 concentration was markedly higher in healthy older women than in healthy young or middle-aged women (by approximately 3- and 2-fold, respectively). In healthy older women, we also measured plasma ET-1 concentration after 3 mo of aerobic exercise (cycling on a leg ergometer at 80% of ventilatory threshold for 30 min, 5 days/wk). Regular exercise significantly decreased plasma ET-1 concentration in the healthy older women (2.22 +/- 0.16 pg/ml, P < 0.01) and also significantly reduced their blood pressure. The present study suggests that regular aerobic-endurance exercise reduces plasma ET-1 concentration in older humans, and this reduction in plasma ET-1 concentration may have beneficial effects on the cardiovascular system (i.e., prevention of progression of hypertension and/or atherosclerosis by endogenous ET-1).     

Skeletal muscle oxidative capacity in young and older women and men.

It has been suggested that a decline in skeletal muscle oxidative capacity is a general consequence of aging in humans. However, previous studies have not always controlled for the effects of varying levels of physical activity on muscle oxidative capacity. To test the hypothesis that, when matched for comparable habitual physical activity levels, there would be no age-related decline in the oxidative capacity of a locomotor muscle, the postexercise recovery time of phosphocreatine was compared in the tibialis anterior muscle of young [n = 19; 33.8 +/- 4.8 (SD) yr] and older [n = 18; 75.5 +/- 4.5 yr] healthy women and men of similar, relatively low, activity levels. The intramuscular metabolic measurements were accomplished by using phosphorus magnetic resonance spectroscopy. The results indicate that there was no age effect on the postexercise recovery time of phosphocreatine recovery, thus supporting the stated hypothesis. These data suggest that there is no requisite decline in skeletal muscle oxidative capacity with aging in humans, at least through the seventh decade.     

Molecular and physiological manifestations and measurement of aging in humans

Biological aging is associated with a reduction in the reparative and regenerative potential in tissues and organs. This reduction manifests as a decreased physiological reserve in response to stress (termed homeostenosis) and a time‐dependent failure of complex molecular mechanisms that cumulatively create disorder. Aging inevitably occurs with time in all organisms and emerges on a molecular, cellular, organ, and organismal level with genetic, epigenetic, and environmental modulators. Individuals with the same chronological age exhibit differential trajectories of age‐related decline, and it follows that we should assess biological age distinctly from chronological age. In this review, we outline mechanisms of aging with attention to well‐described molecular and cellular hallmarks and discuss physiological changes of aging at the organ‐system level. We suggest methods to measure aging with attention to both molecular biology (e.g., telomere length and epigenetic marks) and physiological function (e.g., lung function and echocardiographic measurements). Finally, we propose a framework to integrate these molecular and physiological data into a composite score that measures biological aging in humans. Understanding the molecular and physiological phenomena that drive the complex and multifactorial processes underlying the variable pace of biological aging in humans will inform how researchers assess and investigate health and disease over the life course. This composite biological age score could be of use to researchers seeking to characterize normal, accelerated, and exceptionally successful aging as well as to assess the effect of interventions aimed at modulating human aging.     

Measurement of aortic input impedance in mice: effects of age on aortic stiffness

Mice are used with increasing frequency as models of human cardiovascular diseases, but significant gaps exist in our knowledge of vascular function in the aging mouse. We determined aortic input impedance spectra, pulse wave velocity, and augmentation index in adult (8-mo-old) and old (29-mo-old) mice to determine whether arterial stiffening occurred with age in mice as it does in humans. Pressure and blood velocity signals measured simultaneously from the same location in the ascending aorta were used to determine input impedance spectra (0-10 harmonics). The first minimum of the impedance modulus occurred at the second harmonic in adult mice but shifted to the fourth harmonic in old mice. Characteristic impedance (average of 2nd-10th harmonic) was 57% higher in old mice: 471 +/- 62 vs. 299 +/- 10 (SE) dyn.s.cm-3 (P < 0.05). Pulse pressure and augmentation index, determined from the aortic pressure signals, were also higher in old mice: 42 +/- 2.2 vs. 29 +/- 4.9 mmHg (P < 0.05) and 37 +/- 5 vs. 14 +/- 2% (P < 0.005). Aortic pulse wave velocity measured from the timing of upstrokes of the Doppler velocity signals was 45% higher in old mice: 416 +/- 22 vs. 286 +/- 14 cm/s (n = 3, P < 0.01). These results reproduce age-related findings reported in humans and confirm that mice may be used as models of age-related vascular stiffening.     

Effects of age and gender on finger coordination in MVC and submaximal force-matching tasks.

The objective of the study is to examine the effects of age and gender on finger coordination. Twelve young (24 +/- 8 yr; 6 men and 6 women) and 12 elderly (75 +/- 5 yr; 6 men and 6 women) subjects performed single-finger maximal contraction [maximal voluntary contraction (MVC)], four-finger MVC, and four-finger ramp force production tasks by pressing on individual force transducers. A drop in the force of individual fingers during four-finger MVC tasks compared with single-finger MVC tasks (force deficit) was larger, whereas unintended force production by other fingers during single-finger MVC tasks (enslaving) was smaller, in elderly than in young subjects and in women than in men. Force deficit was smaller and enslaving was larger in subjects with higher peak force. During the ramp task, the difference between the variance of total force and the sum of variances of individual forces showed a logarithmic relation to the level of total force, across all subject groups. These findings suggest that indexes of finger coordination scale with force-generating capabilities across gender and age groups.     

How Aging Affects Grasping Behavior and Pull Strength in Captive Gray Mouse Lemurs (<Emphasis Type="Italic">Microcebus murinus</Emphasis>)

Prehension is essential for animal survival and fitness. It is involved in locomotion and feeding behavior and subject to physical and physiological constraints. Studies of prehension in primates have explored the importance of food properties and of the environment, but aging has rarely been studied although prehensile capacity may deteriorate with age in humans. To test the hypothesis that aging affects grasping abilities and to reveal possible behavioral adaptations to this, we quantified behavioral grasping strategies and pull strength in 10 young adult (2–3 yr old) and 10 aged (7–8 yr old) gray mouse lemurs (Microcebus murinus). We assessed grasping strategies in an experimental cage by quantifying grip types used to grasp static and mobile foods. We measured strength using a Kistler triaxial force platform. Our results show that 1) mobile and static foods affected individuals of different ages in similar ways; 2) older individuals used more mouth grasps than young ones; 3) aged individuals made twice as many attempts as young ones when grasping mobile food items but this difference was not significant; and 4) there were no differences in hand grip strength between age classes but young individuals showed a higher foot pull strength compared to old ones. These data suggest that the observed differences in behavior may be due to a decrease in foot grip strength, which in turn influences stability on narrow branches, forcing animals to use their hands to maintain stability and preventing them from using their hands for food-related tasks.     

Membrane Resonance and Stochastic Resonance Modulate Firing Patterns of Thalamocortical Neurons

We examined the interactions of subthreshold membrane resonance and stochastic resonance using whole-cell patch clamp recordings in thalamocortical neurons of rat brain slices, as well as with a Hodgkin-Huxley-type mathematical model of thalamocortical neurons. The neurons exhibited the subthreshold resonance when stimulated with small amplitude sine wave currents of varying frequency, and stochastic resonance when noise was added to sine wave inputs. Stochastic resonance was manifest as a maximum in signal-to-noise ratio of output response to subthreshold periodic input combined with noise. Stochastic resonance in conjunction with subthreshold resonance resulted in action potential patterns that showed frequency selectivity for periodic inputs. Stochastic resonance was maximal near subthreshold resonance frequency and a high noise level was required for detection of high frequency signals. We speculate that combined membrane and stochastic resonances have physiological utility in coupling synaptic activity to preferred firing frequency and in network synchronization under noise.     

Physiological complexity and system adaptability: evidence from postural control dynamics of older adults

The degree of multiscale complexity in human behavioral regulation, such as that required for postural control, appears to decrease with advanced aging or disease. To help delineate causes and functional consequences of complexity loss, we examined the effects of visual and somatosensory impairment on the complexity of postural sway during quiet standing and its relationship to postural adaptation to cognitive dual tasking. Participants of the MOBILIZE Boston Study were classified into mutually exclusive groups: controls [intact vision and foot somatosensation, n = 299, 76 ± 5 (SD) yr old], visual impairment only (<20/40 vision, n = 81, 77 ± 4 yr old), somatosensory impairment only (inability to perceive 5.07 monofilament on plantar halluxes, n = 48, 80 ± 5 yr old), and combined impairments (n = 25, 80 ± 4 yr old). Postural sway (i.e., center-of-pressure) dynamics were assessed during quiet standing and cognitive dual tasking, and a complexity index was quantified using multiscale entropy analysis. Postural sway speed and area, which did not correlate with complexity, were also computed. During quiet standing, the complexity index (mean ± SD) was highest in controls (9.5 ± 1.2) and successively lower in the visual (9.1 ± 1.1), somatosensory (8.6 ± 1.6), and combined (7.8 ± 1.3) impairment groups (P = 0.001). Dual tasking resulted in increased sway speed and area but reduced complexity (P < 0.01). Lower complexity during quiet standing correlated with greater absolute (R = -0.34, P = 0.002) and percent (R = -0.45, P < 0.001) increases in postural sway speed from quiet standing to dual-tasking conditions. Sensory impairments contributed to decreased postural sway complexity, which reflected reduced adaptive capacity of the postural control system. Relatively low baseline complexity may, therefore, indicate control systems that are more vulnerable to cognitive and other stressors.     

Aging, visual information, and adaptation to task asymmetry in bimanual force coordination

This study investigated the coordination and control strategies that the elderly adopt during a redundant finger force coordination task and how the amount of visual information regulates the coordination patterns. Three age groups (20-24, 65-69, and 75-79 yr) performed a bimanual asymmetric force task. Task asymmetry was manipulated via imposing different coefficients on the finger forces such that the weighted sum of the two index finger forces equaled the total force. The amount of visual information was manipulated by changing the visual information gain of the total force output. Two hypotheses were tested: the reduced adaptability hypothesis predicts that the elderly show less degree of force asymmetry between hands compared with young adults in the asymmetric coefficient conditions, whereas the compensatory hypothesis predicts that the elderly exhibit more asymmetric force coordination patterns with asymmetric coefficients. Under the compensatory hypothesis, two contrasting directions of force sharing strategies (i.e., more efficient coordination strategy and minimum variance strategy) are expected. A deteriorated task performance (high performance error and force variability) was found in the two elderly groups, but enhanced visual information improved the task performance in all age groups. With low visual information gain, the elderly showed reduced adaptability (i.e., less asymmetric forces between hands) to the unequal weighting coefficients, which supported the reduced adaptability hypothesis; however, the elderly revealed the same degree of adaptation as the young group under high visual gain. The findings are consistent with the notion that the age-related reorganization of force coordination and control patterns is mediated by visual information and, more generally, the interactive influence of multiple categories of constraints.     

Accumulation of calcium in the arteries of Japanese monkey

To examine whether the calcium accumulation in the arteries is related to the way of walk or not, the calcium contents were determined in various arteries of Japanese monkeys of quadrupedal walk by inductively coupled plasma-atomic emission spectrometry. Japanese monkeys consisted of five males and four females, ranging in age from 2 to 29 yr. Age-related changes of the calcium content were examined in various monkey arteries. Significant relationships between age and calcium content were found in the arteries, such as the axillary, brachial, radial, subclavian, common carotid, common iliac, and femoral arteries, but not statistically in the thoracic and abdominal aortas, ulnar, external iliac, internal iliac, popliteal, and tibial arteries. The average contents of calcium were compared between the two groups of the monkeys below 14 yr and over 24 yr of age. Below 14 yr, the calcium content was a little higher in the arteries, such as the common, external and internal iliac, and femoral arteries than that of the other ones. Over 24 yr, the calcium content increased remarkably in the arteries, such as the thoracic aorta, common, internal and external iliac, common carotid, and subclavian arteries. The calcium contents of the thoracic aorta, common, internal and external iliac, common carotid, and subclavian arteries increased by more than two times over 24 yr compared with those below 14 yr. In a comparison between the calcium contents of the arteries in the anatomically corresponding regions of the upper and lower limbs, no statistically significant differences were found in the subjects over 24 yr as well as the subjects 2–29 yr of age. The calcium accumulation in the arteries of monkeys with aging was different from those in the arteries of humans, because in the case of human, a very high accumulation of calcium occurred in the arteries of the lower limb with aging in comparison with those in the upper limbs. Therefore, it is likely that different ways of walk or different species are partly affected in the calcium accumulation in the arteries with aging.     

Resolution of patch capacitance recordings and of fusion pore conductances in small vesicles

We investigated the noise levels in cell-attached patch capacitance recordings with a lock-in amplifier. The capacitance noise level decreases with increasing sine wave frequency up to 20-40 kHz. With a 20-mV rms sine wave the rms noise level above 8 kHz is <50 aF. With increasing sine wave amplitudes a further reduction down to 14 aF could be achieved. Capacitance measurements with a lock-in amplifier may also be used to measure the conductance of fusion pores connecting the vesicular lumen to the extracellular space. It is estimated that at noise levels of 14 aF fusion pore conductances between 20 pS and 700 pS may be resolved in vesicles with 380-aF capacitance by using a 50-kHz sine wave. This corresponds to vesicles with a approximately 110-nm diameter. It is suggested that with low-noise techniques fusion pores may be detectable in vesicles approaching the size of large synaptic vesicles.