We hypothesize that the attenuated hypertrophic response in old mouse muscle is (1) partly due to a reduced capillarization and angiogenesis, which is (2) accompanied by a reduced oxidative capacity and fatigue resistance in old control and overloaded muscles, that (3) can be rescued by the antioxidant resveratrol. To investigate this, the hypertrophic response, capillarization, oxidative capacity, and fatigue resistance of m. plantaris were compared in 9- and 25-month-old non-treated and 25-month-old resveratrol-treated mice. Overload increased the local capillary-to-fiber ratio less in old (15 %) than in adult (59 %) muscle (P < 0.05). Although muscles of old mice had a higher succinate dehydrogenase (SDH) activity (P < 0.05) and a slower fiber type profile (P < 0.05), the isometric fatigue resistance was similar in 9- and 25-month-old mice. In both age groups, the fatigue resistance was increased to the same extent after overload (P < 0.01), without a significant change in SDH activity, but an increased capillary density (P < 0.05). Attenuated angiogenesis during overload may contribute to the attenuated hypertrophic response in old age. Neither was rescued by resveratrol supplementation. Changes in fatigue resistance with overload and aging were dissociated from changes in SDH activity, but paralleled those in capillarization. This suggests that capillarization plays a more important role in fatigue resistance than oxidative capacity.

Force characteristics of skeletal muscle of knockout mice lacking creatine (Cr) due to a deletion of guanidinoacetate methyltransferase (GAMT) were studied in situ. Medial gastrocnemius muscles of anesthetized GAMT-deficient (GAMT Ϫ/Ϫ ) and control (Con) littermates were stimulated at optimum length via the sciatic nerve at different stimulation frequencies . GAMT Ϫ/Ϫ mice showed reduced maximal tetanic and twitch force, reduced relative force at 60 Hz, and increased relaxation times. High-intensity fatigue protocols consisting of 30 successive isometric or dynamic contractions showed a strong reduction in force at the beginning of the series in GAMT Ϫ/Ϫ mice, followed by a smaller reduction compared with Con littermates toward the end of the series. Cr supplementation for 2 days in GAMT Ϫ/Ϫ animals (GAMT Cr Ϫ/Ϫ ) resulted in normalization to Con values for relaxation times, relative force at lower stimulation frequencies, and relative force during 30 isometric contractions. Force per muscle mass, however, remained decreased. Furthermore, GAMT Cr Ϫ/Ϫ mice showed differences compared with both Con and unsupplemented animals in maximal rates of force rise and relaxation times during the isometric protocol as well as in force during the dynamic protocol. Our results show that the absence of Cr plays a direct role in relaxation times, maximal rate of force rise, and force production during high-intensity fatigue protocols. The lower force per muscle mass, however, is probably caused by other factors; i.e., high intracellular guanidinoacetate concentrations. energy metabolism; creatine; fatigue; force characteristics THE CREATINE KINASE (CK) reaction, where creatine (Cr) and ATP are reversibly catalyzed to form phosphocreatine (PCr), ADP, and a hydrogen ion, is considered to be important for energy metabolism during muscular exercise (e.g., 15, 32). This so-called PCr-CK system is thought to play a key role in keeping ATP-to-ADP ratios balanced and possibly also in the transport of high-energy phosphates through the cytosol (2,33,35). In skeletal muscle, two major isoforms of CK are present: mouse muscle (MM-CK) in the cytosol and skeletal (ScCKmit) in the intermembrane space of the mitochondria (33).In the past decade, the significance of the PCr-CK system on muscle performance and energy metabolism has been studied in muscles of mice lacking either one or both of the isoforms of CK that are present in muscle (7,9,16,22,25,28,30), and even earlier in rats fed analogs of Cr (e.g

The age-related decline in muscle function contributes to the movement limitations in daily life in old age. The age-related loss in muscle force is attributable to loss of myofibers, myofiber atrophy, and a reduction in specific force. The contribution of each of these determinants to muscle weakness in old age is, however, largely unknown. The objective of this study is to determine whether a loss in myofiber number, myofiber atrophy, and a reduction in specific muscle force contribute to the age-related loss of muscle force in 25-month-old mouse. Maximal isometric force of in situ m. plantaris of C57BL/6J male adult (9 months) and old (25 months) mice was determined and related to myofiber number, myofiber size, intramuscular connective tissue content, and proportion of denervated myofibers. Isometric maximal plantaris muscle force was 13 % lower in old than adult mice (0.97±0.05 N vs. 0.84±0.03 N; P<0.05). M. plantaris mass of old mice was not significantly smaller than that of adult mice. There was also no significant myofiber atrophy or myofiber loss. Specific muscle force of old mice was 25 % lower than that of adult mice (0.55±0.05 vs. 0.41± 0.03 N·mm −2 , P<0.01). In addition, with age, the proportion of type IIB myofibers decreased (43.6 vs. 38.4 %, respectively), while the connective tissue content increased (11.6 vs. 16.4 %, respectively). The agerelated reduction in maximal isometric plantaris muscle force in 25-month-old male C57BL/6J mice is mainly attributable to a reduction in specific force, which is for 5 % explicable by an age-related increase in connective tissue, rather than myofiber atrophy and myofiber loss.

During many movements (e.g., running, jumping, and kicking) there is little time for skeletal muscles to build up force, thus rapid force development is important. The length dependency of isometric force development was investigated in maximally activated rat medial gastrocnemius muscles in situ with intact blood flow at 35 degrees C. Depending on time available for muscle activation, the length dependency of force development was expected to differ from that of the maximal isometric force (F(max)) reached much later during the contraction. During isometric force development in intact muscle-tendon preparations, the contractile elements actually shortened. Therefore, similar to previous findings on shortening contractions, it was hypothesized that maximal rate of force development (MRFD) would be obtained at a length below the optimum (L(o)) for maximal isometric force production. To measure the effect of the entire time history of activation, force time integrals (FTIs) for different activation times (10-50 ms) were also calculated. The highest MRFD was obtained 1.94 +/- 0.42 mm below (p < 0.05) L(o). When expressed relative to F(max) obtained at each individual length, the optimum was found at L(o) - 4.4 mm. For FTI 10 ms and FTI 20 ms, optimum length was obtained at approximately 2 and 1 mm above (p < 0.05) L(o), respectively, whereas the optima for FTI 30, 40, and 50 ms were approximately 1 mm below (p < 0.05) L(o). In addition, at short lengths (< L(o) - 4 mm) and for all activation times FTIs were relatively more decreased than F(max). In conclusion, length dependency of force output during rapid force development differed from that of maximal isometric force; specifically, MRFD was obtained 2 mm below L(o).