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).

The histologic features of aging muscle suggest that denervation contributes to atrophy, that immobility accelerates the process, and that routine exercise may protect against loss of motor units and muscle tissue. Here, we compared muscle biopsies from sedentary and physically active seniors and found that seniors with a long history of high-level recreational activity up to the time of muscle biopsy had 1) lower loss of muscle strength versus young men (32% loss in physically active vs 51% loss in sedentary seniors); 2) fewer small angulated (denervated) myofibers; 3) a higher percentage of fiber-type groups (reinnervated muscle fibers) that were almost exclusive of the slow type; and 4) sparse normal-size muscle fibers coexpressing fast and slow myosin heavy chains, which is not compatible with exercise-driven muscle-type transformation. The biopsies from the old physically active seniors varied from sparse fiber-type groupings to almost fully transformed muscle, suggesting that coexpressing fibers appear to fill gaps. Altogether, the data show that long-term physical activity promotes reinnervation of muscle fibers and suggest that decades of high-level exercise allow the body to adapt to age-related denervation by saving otherwise lost muscle fibers through selective recruitment to slow motor units. These effects on size and structure of myofibers may delay functional decline in late aging.

A time-of-day influence on the neuromuscular response to strength training has been previously reported. However, no scientific study has examined the influence of the time of day when strength training is performed on hormonal adaptations. Therefore, the primary purpose of this study was to examine the effects of time-of-day-specific strength training on resting serum concentrations and diurnal patterns of testosterone (T) and cortisol (CORT) as well as maximum isometric strength of knee extensors. Thirty eight diurnally active healthy, previously untrained men (age 20-45 yrs) underwent a ten-week preparatory strength training period when sessions were conducted between 17:00-19:00 h. Thereafter, these subjects were randomized into either a morning (n=20, training times 07:00-09:00 h) or afternoon (n=18, 7:00-19:00 h) training group for another ten-week period of time-of-day-specific training (TST). Isometric unilateral knee extension peak torque (MVC) was measured at 07:00, 12:00, 17:00, and 20:30 h over two consecutive days (Day 1 & Day 2) before and after TST. Blood samples were obtained before each clock-time measurement to assess resting serum T and CORT concentrations. A matched control group (n=11) did not train but participated in the tests. Serum T and CORT concentrations significantly declined from 07:00 to 20:30 h on all test days (Time effect, p<.001). Serum CORT at 07:00 h was significantly higher on Day 1 than Day 2 in the control and afternoon group, both in Pre and Post conditions (Day x Time interaction, p<.01). In the morning group, a similar day-to-day difference was present in the Pre but not Post conditions (Time x Group interaction, p<.05). MVC significantly increased after TST in both the morning and afternoon groups (Pre to Post effect, p<.001). In both groups, a typical diurnal variation in MVC (Time effect, p<.001) was found, especially on Day 2 in the Pre condition, and this feature persisted from Pre to Post in the afternoon group. In the morning group, however, diurnal variation was reduced after TST on both Day 1 and Day 2 (Pre to PostxDay x TimexGroup interaction, p<.05). In conclusion, 10 weeks of morning time-of-day-specific strength training resulted in reduced morning resting CORT concentrations, presumably as a result of decreased masking effects of anticipatory psychological stress prior to the morning testing. The typical diurnal pattern of maximum isometric strength was blunted by the TST period in the morning but not the afternoon group. However, the TST period had no significant effect on the resting total T concentration and its diurnal pattern and on the absolute increase in maximum strength.

Sarcopenia is the age-related loss of muscle mass and function, reducing force generation and mobility in the elderlies. Contributing factors include a severe decrease in both myofiber size and number as well as a decrease in the number of motor neurons innervating muscle fibers (mainly of fast type) which is sometimes accompanied by reinnervation of surviving slow type motor neurons (motor unit remodeling). Reduced mobility and functional limitations characterizing aging can promote a more sedentary lifestyle for older individuals, leading to a vicious circle further worsening muscle performance and the patients’ quality of life, predisposing them to an increased risk of disability, and mortality. Several longitudinal studies have shown that regular exercise may extend life expectancy and reduce morbidity in aging people. Based on these findings, the Interreg IVa project aimed to recruit sedentary seniors with a normal life style and to train them for 9 weeks with either leg press (LP) exercise or electrical stimulation (ES). Before and at the end of both training periods, all the subjects were submitted to mobility functional tests and muscle biopsies from the Vastus Lateralis muscles of both legs. No signs of muscle damage and/or of inflammation were observed in muscle biopsies after the training. Functional tests showed that both LP and ES induced improvements of force and mobility of the trained subjects. Morphometrical and immunofluorescent analyses performed on muscle biopsies showed that ES significantly increased the size of fast type muscle fibers (p<0.001), together with a significant increase in the number of Pax7 and NCAM positive satellite cells (p<0.005). A significant decrease of slow type fiber diameter was observed in both ES and LP trained subjects (p<0.001). Altogether these results demonstrate the effectiveness of physical exercise either voluntary (LP) or passive (ES) to improve the functional performances of aging muscles. Here ES is demonstrated to be a safe home-based method to counteract fast type fiber atrophy, typically associated with aging skeletal muscle.