Lifelong physical exercise delays age-associated skeletal muscle decline.

Aging is usually accompanied by a significant reduction in muscle mass and force. To determine the relative contribution of inactivity and aging per se to this decay, we compared muscle function and structure in (a) male participants belonging to a group of well-trained seniors (average of 70 years) who exercised regularly in their previous 30 years and (b) age-matched healthy sedentary seniors with (c) active young men (average of 27 years). The results collected show that relative to their sedentary cohorts, muscle from senior sportsmen have: (a) greater maximal isometric force and function, (b) better preserved fiber morphology and ultrastructure of intracellular organelles involved in Ca(2+) handling and ATP production, (c) preserved muscle fibers size resulting from fiber rescue by reinnervation, and (d) lowered expression of genes related to autophagy and reactive oxygen species detoxification. All together, our results indicate that: (a) skeletal muscle of senior sportsmen is actually more similar to that of adults than to that of age-matched sedentaries and (b) signaling pathways controlling muscle mass and metabolism are differently modulated in senior sportsmen to guarantee maintenance of skeletal muscle structure, function, bioenergetic characteristics, and phenotype. Thus, regular physical activity is a good strategy to attenuate age-related general decay of muscle structure and function (ClinicalTrials.gov: NCT01679977).

New hopes for dynamic cardiomyoplasty from use of Doppler flow wire in evaluation of demand stimulation.

BACKGROUND: There are no data regarding real cardiac assistance in demand dynamic cardiomyoplasty (DDCMP). A test of the use of Doppler flow wire is presented to demonstrate cardiac assistance in DDCMP. METHODS: Comparative study in hospitalized care. A peripheral Flex Doppler flow wire of 0.018 inch was advanced through a 4F introducer femoral arterial in seven DDCMP patients (age=57.1+/-6.2 years; NYHA= 1.4+/-0.5). A short period of 10 sec with stimulator off and a following period of 15 sec with clinical stimulation were recorded. We measured the maximum peak aortic flow velocity (MPAV) in all beats. Latissimus dorsi (LD) mechanogram was simultaneously recorded. RESULTS: Statistical analysis showed an increase not only in MPAV in assisted period versus rest, but also in assisted beats versus unassisted (8.42+/-6.98% and 7.55+/-3.07%). CONCLUSIONS: Intravascular Doppler proved real systolic assistance in DDCMP; in DDCMP systolic assistance is correlated to the LD wrap speed of contraction, suggesting that demand stimulation could be the most effective protocol in dynamic cardiomyoplasty.

Activity-rest stimulation of latissimus dorsi for cardiomyoplasty: 1-year results in sheep.

BACKGROUND: In dynamic cardiomyoplasty electro-stimulation achieves full transformation of the latissimus dorsi (LD); therefore, its slowness limits the systolic support. Daily activity-rest could maintain partial transformation of the LD. METHODS: Sheep LD were burst-stimulated either 10 or 24 hours/day. Before and 2, 4, 6, and 12 months after stimulation, LD power output, fatigue resistance, and tetanic fusion frequency were assessed. Latissimus dorsi were biopsied at 6 months, and sheep sacrificed at 12 months. RESULTS: After 1 year of 10 hours/day stimulation LD was substantially conserved and contained large amounts of fast type myosin. From 2 months to 1 year of stimulation the power per muscle of the daily rested LD was greater than that of the left ventricle, being three to four times higher than in the 24-hour/day stimulation. CONCLUSIONS: If extended to humans, these results could be the rationale for the need of a cardiomyostimulator, whose discontinuous activity could offer to patients the long-standing advantage of a faster and powerful muscle contraction.

[The effect of the functional electrostimulation of rat fast and slow muscles on the structural state of actin in the thin filaments of a ghost muscle fiber]. / Vliianie funktsional'noi élektrostimuliatsii bystrykh i medlennykh myshts krysy na strukturnoe sostoianie aktina v tonkikh nitiakh tenevogo myshechnogo volokna.

The effect of electrostimulation of fast (EDL) and slow (SOL) rat muscles on the orientation and mobility of fluorescent probes rhodamine-phalloidine and 1.5-IAEDANS (N-iodoacetyl-N'-(5-sulpho-1-naphtyl)-ethylenediamine), located in various parts of actin molecule, has been studied by polarized microfluorimetry techniques. Muscles were stimulated at 20 Hz with the pulse width of 0.3 msec, some muscles were treated for 6 h during the first day, the other muscles for 6 h a day during the next 4 days before glycerinization. Then muscle fibres freed by the extraction of myosin, tropomyosin and troponin (ghost fibres) were used. It was shown that the binding of myosin subfragment 1 (S1) to actin induced the changes in polarized fluorescence of the fibres. The analysis of the obtained data showed that the formation of actomyosin complex in stimulated muscles resulted in increasing the angle between the thin filaments and the emission dipole of rhodamine-phalloidine, as well as in decreasing the mobility of this dye. In the experiments with the 1.5-IAEDANS label, the angle of the emission dipole decreased, while the label mobility increased. It was suggested that the orientation of domains in actomyosin complex changes following the electrostimulation to affect both the conformational state of F-actin in thin filaments of ghost fibres and actin-myosin interaction.

Isomyosin changes after functional electrostimulation of denervated sheep muscle.

Isomyosin analyses by biochemical, immunochemical, and histochemical investigations have been carried out in five sheep following unilateral recurrent laryngeal nerve paralysis and direct functional electrostimulation of the denervated cricoarytenoid posterior muscle. Myosin light chains were identified by two-dimensional gel electrophoresis. Myosin heavy chains were analyzed by one-dimensional SDS-polyacrylamide gel electrophoresis. Slow myosin heavy chain was identified by orthogonal peptide mapping and immunochemistry. The stimulation effect at cellular level was determined using adenosine triphosphatase (ATPase) histochemistry. A dramatic increase of the type 1 fiber area (slow, fatigue-resistant fibers) could be seen after many weeks of an increasing regime of low-frequency direct electrical stimulation. Biochemically, the amount of slow myosin was always higher than in normal muscles. Some muscles were transformed almost completely to the slow type. At the time they were studied and with the methods employed, the expression of embryonic isomyosin was not observed. In conclusion, after numerous weeks of maintained functional activity, elicited by direct electrostimulation, the denervated muscle regionally showed areas of hypertrophy or at least lack of atrophy of slow myofibers without major signs of muscle damage.

Slow-like electrostimulation switches on slow myosin in denervated fast muscle.

Adult fast and slow skeletal muscles are composed of a large number of fibers with different physiological and biochemical properties that under neuronal control can respond in a plastic manner to a variety of stimuli. Although muscle cells synthesize muscle-specific contractile proteins in the absence of motoneurons, after innervation the neuron controls the particular set of isoforms subsequently synthesized. However, agreement has not been reached on the mechanism, either chemotrophic or impulse-mediated, by which the nerve influences gene expression in the muscle. Here we report the effect on isomyosins of continuous, low-frequency (a protocol mimicking the discharge pattern of the slow motoneuron) direct electrical stimulation of a permanently denervated fast muscle, the extensor digitorum longus of adult rat. After several weeks, unlike sham-stimulated muscle, the stimulated muscle showed a dramatic increase of the slow myosin light and heavy chains. Myosin light chains were identified by two-dimensional gel electrophoresis. The slow myosin heavy chain was clearly distinguished from fast and embryonic types by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and orthogonal peptide mapping. The myosin change could be restricted to a portion of the muscle by the position of the stimulating electrodes. Taking into account the morphologic appearance of the electrostimulated muscle and the large body of evidence demonstrating the absolute dependence of slow myosin on specific innervation, our observations indicate that at least the slow motoneuron influences the isomyosin genes' expression by the kind of activity it imposes on developing muscle fibers.

[Functional electrostimulation of the denervated posticus muscle in an animal experiment: histo- and biochemical results]. / Funktionelle Elektrostimulation des denervierten M. posticus im Tierversuch: Histo- und biochemische Ergebnisse.

Histochemical and biochemical investigations have been carried out in 2 sheep following unilateral recurrent laryngeal nerve paralysis and direct electrical stimulation of the denervated posticus muscles. The stimulation effect was determined histochemically (standard ATP-ase staining) and compared with the fibre pattern of normal posticus muscles. In addition, one-dimensional gel electrophoresis of myosin heavy-chain isoforms was carried out and correlated with the histochemical results. A dramatic increase of type I fibres could be seen after long-term low-frequency direct electrical stimulation of denervated posticus muscles of the sheep. Biochemically the amount of slow myosin heavy-chain isoforms was higher than in normal muscles.