The purpose is to characterize and explain age associated losses of muscle strength, understand the effects of age and gender on the exercise response to exercise, and to examine the phyiological contributions of motor units to strength production.1. Characterization of longitudinal strength changes in the BLSA. Over the past year, we have reported cross sectional and longitudinal changes in the force generated per unit of muscle (muscle quality). Depending on the means of measuring muscle mass and strength, we found that muscle quality either declined with age or remained unchanged. Furthermore, longitudinal analysis found no change in muscle quality. The findings argued that factors other than muscle mass contribute to age-associated strength loss. In a separate study, we demonstrated that changes in peripheral nerve function as assessed by nerve conduction velocity were found to have a small contribution to the loss independent of mass. An unresolved issue is the degree that such age-associated changes in strength alter functional performance. We examined the question by comparing timed gait to knee strength in subjects aged 20-90. Rapid gait speed was found to increase linearly to a strength of about 200 Nm, with no further changes in speed at higher strength levels. The plateauing of the strength gait speed curve, argues that 200 Nm represents a threshold forfunctional reserve, i.e. an excess in physiological function that does not increase performance. What was particularly revealing was that 10-15% of men fell above this plateau level, while none of the women reached this level. Also, a plateau was found for normal gait speed. However, at normal speed, 20% of women fell on the plateau, as well as 40% of men. The striking observation is that women are dependent on the strength to gait speed linear relationship to a far greater extent than are men. Age-associated changes in strength should have a greater negative impact on womens gait than on mens gait, particularly at faster speeds. 2. Comparison of exercise response to resistive strength training in young and old subjects. After 9 weeks of resistive strength training both young and old, women and men showed approximately a 25% to 35% increase in muscle strength based on 1 RM with younger subjects showing a greater increase. After 20 weeks of detraining, both age groups continued to be stronger than at baseline. Unfortunately, the older women did not maintain the increases as well as the other three groups. The increase in strength was associated with muscle hypertrophy that was greater in men than women, but no difference based on age. The increases were not found to be associated with increases in muscle damage in either young or old men. Isometric strength did not significantly increase, but during isometric exertion, a change occurred in motor unit activation with smaller units being used to generate the same force levels after as compared to before training. Other benefits may arise from strength training programs. Following 24 weeks of total body training, a transient decline was observed in blood pressure that lasted for up to 48 hours. However, following the 24 weeks of total body training, there were no reductions in plasma fasting glucose levels, but men seemed to blunt their insulin response during oral glucose tolerance test. Resting metabolic rates were found to increased in both young and old subjects, but this primarily resulted from increases in the men. These increases were directly related to changes in fat free mass. Levels of activity as judged by triaxial accelerometer, and by questionnaire did not change in response to exercise. The total body training resulted in improved bone mineral density of the femoral region in young men and women and increases in lumbar spine bone mineral density in young women, but does not change regional bone mineral density in older healthy men and women. 3. Examination of the motor unit and its relationship to muscle strength and exercise response. Decomposition- enhanced spike-triggered averaging was applied to the vastus medialis muscle to examine size distribution of surface-detected motor unit action potentials and firing rates at various voluntarily generated force levels. Amplitude increased linearly with increasing knee extension force. Firing rate showed small increases to 30% of maximal knee extension force, and rose more rapidly at higher force levels. Average motor unit amplitude and firing rate accounted for approximately 70% of the variance in muscle force generation. During fatiguing submaximal isometric force at 30% of maximal a progressive increase in motor unit amplitude occurred with a gradual decline in firing rate, consistent with the concept of muscle wisdom advocated by Marsden and Merton.