Can lifelong endurance exercise improve ageing through beneficial effects on circadian timing function, muscular performance and health status in men? Protocol for a comparative cross-sectional study.

A well-synchronized circadian system is a manifestation of an individual's health. A gradual weakening of the circadian timing function characterizes aging. Regular exercise has been suggested as a modality to improve many detrimental changes associated with aging. Therefore, we aim to examine the benefits and risks of lifelong endurance exercise on age-dependent changes in the circadian time-keeping function, the performance of the muscular system and health status. The study protocol has a comparative cross-sectional design, including groups of senior (65 to 75 years old, n=16) and young (20-30 years old, n=16) endurance runners and triathletes. Age-matched groups of young and elderly sedentary men are included as controls. The circadian function is evaluated mainly by measurement of urinary 6-sulphatoxymelatonin, a metabolite of the hormone melatonin shown to participate in the modulation of sleep cycles. The 6-sulphatoxymelatonin will be assessed in urine samples collected upon awakening in the morning and in the late evening, as a marker of melatonin production. In addition, sleep/activity rhythms and sleep quality will be measured by wrist actigraphy. Performance of the muscular system will be assessed by examination of muscular strength and quantifying of gene expression in the skeletal muscle tissue samples. Health status and age-induced reduction in immune function are to be analysed via the balance of pro- and anti-inflammatory immune markers in the plasma and skeletal muscle, body composition, bone density and physical fitness.

Benefits of Eccentric Training with Emphasis on Demands of Daily Living Activities and Feasibility in Older Adults: A Literature Review.

Aging is associated with a decline in physical capabilities and several other health-related conditions. One of the most common age-related processes is sarcopenia. Sarcopenia is usually accompanied with a decline in skeletal muscle mass and physical functioning. A decrease in these markers usually impacts basic daily living activities (DLAs), which become somewhat harder to accomplish for older individuals. Several research studies have examined the demands of DLA in older individuals with results indicating that activities such as walking, sitting, standing, stair climbing, stair descending, and running generate high demands on older adults. The forces that act on individuals are in most cases equal or multiple times higher relative to their body mass. For instance, it was reported that the GRF (ground reaction force) during stair descent ranged from 1.43 to 1.50 of BW (body weight) in an older population. Even higher demands were recorded during other related activities. These demands of DLA raise the question of appropriate rehabilitative or training management procedures. During the past decades, an eccentric form of resistance training gained popularity due to its effectiveness and lower metabolic demands, which seems to be an appropriate method to develop and maintain a basic level of strength capabilities in higher age. Multiple factors of eccentric training have been examined including modality of exercise, intensity, frequency, and safety of the elderly. Several modalities of eccentric exercise have been shown to be effective including traditional methods, as well as machine-based ones, with or without using some equipment. The studies included in this review varied in intensity from low to high; however, the most frequently used intensity was ≥50% of the maximal eccentric strength during two or three eccentric sessions per week. Importantly, the prevalence of injury of older adults appears to have been low to none, highlighting the safety of this approach. In summary, eccentric training prescriptions for older adults should consider the demands of DLA and the characteristics of the elderly for appropriate management of training recommendations.

Aging and Possible Benefits or Negatives of Lifelong Endurance Running: How Master Male Athletes Differ from Young Athletes and Elderly Sedentary?

Regular physical activity, recommended by the WHO, is crucial in maintaining a good physical fitness level and health status and slows down the effects of aging. However, there is a lack of knowledge of whether lifelong endurance running, with a volume and frequency above the WHO limits, still brings the same benefits, or several negative effects too. The present study aims to examine the protentional benefits and risks of lifelong endurance running training in Master male athletes, as this level of physical activity is above the WHO recommendations. Within the study, four main groups of participants will be included: (1) endurance-trained master athletes, (2) endurance-trained young athletes, (3) young sedentary adults, and (4) elderly sedentary. Both groups of athletes are strictly marathon runners, who are still actively running. The broad spectrum of the diagnostic tests, from the questionnaires, physical fitness testing, and blood sampling to muscle biopsy, will be performed to obtain the possibility of complexly analyzing the effects of lifelong endurance physical activity on the human body and aging. Moreover, the study will try to discover and explain new relationships between endurance running and diagnostic parameters, not only within aging.

Linear Motor Driven Leg-Press Dynamometer for Testing, Training, and Rehabilitation: A Scoping Review with a Focus on the Concept of Serial Stretch Loading.

BACKGROUND: The purpose of this scoping review was to analyze the evidence of acute and long-term effects of the application of leg-press strength training with or without serial stretch-loading stimuli on various biomechanical and physiological outcomes. METHODS: This review was performed in accordance with PRISMA for Scoping Reviews recommendations, and two researchers independently searched the following databases: PubMed, Web of Science, Scopus, ScienceDirect, ProQuest, Cochrane, and Google Scholar. All studies that used unique leg-press device for testing, acute responses and long-term adaptation were included in this review, irrespective of the measured outcomes. A total of 13 studies were included in this review, with 5 focused on the testing capabilities of the device and acute training responses and 8 focused on the long-term adaptations in various physical and physiological outcomes. RESULTS: Regarding the acute responses after leg-press strength training with or without serial stretch-loading stimuli, visible changes were observed in the muscle force, rate of force development, and hormonal concentrations between pre- and postmenopausal women (only one study). Long-term studies revealed different training adaptations after performing leg-press strength training with unique serial stretch-loading stimuli. A positive trend for leg-press strength training with serial stretch-loading was recorded in the young population and athletes; however, more variable training effects favoring one or the other approach were achieved in the older population. CONCLUSIONS: In summary, this review shows the uniqueness and usability of a leg-press device that is capable of various exercising modes, including special serial stretch-loading stimuli. The use of this device can serve as a positive addition to training regiments, and the main application appears to be suitable for rehabilitation needs.

Reinnervation of Vastus lateralis is increased significantly in seniors (70-years old) with a lifelong history of high-level exercise (2013, revisited here in 2022).

In 2013 we presented results showing that at the histological level lifelong increased physical activity promotes reinnervation of muscle fibers in aging muscles. Indeed, in muscle biopsies from 70-year old men with a lifelong history of high-level physical activity, we observed a considerable increase in fiber-type groupings (F-TG), almost exclusively of the slow type. Slow-type transformation by denervation-reinnervation in senior sportsmen seems to fluctuate from those with scarce fiber-type transformation and groupings to almost fully transformed muscle, going through a process in which isolated fibers co-expressing fast and slow Myosin Heavy Chains (MHCs) seems to fill the gaps. Taken together, our results suggest that, beyond the direct effects of aging on the muscle fibers, changes occurring in skeletal muscle tissue appear to be largely, although not solely, a result of sparse denervation-reinnervation. The lifelong exercise allows the body to adapt to the consequences of the age-related denervation and to preserve muscle structure and function by saving otherwise lost muscle fibers through recruitment to different, mainly slow, motor units. These beneficial effects of high-level life-long exercise on motoneurons, specifically on the slow type motoneurones that are those with higher daily activity, and on muscle fibers, serve to maintain size, structure and function of muscles, delaying the functional decline and loss of independence that are commonly seen in late aging. Several studies of independent reserchers with independent analyses confirmed and cited our 2013 results. Thus, the results we presented in our paper in 2013 seem to have held up rather well.

Effects of Short- and Long-Term Aerobic-Strength Training and Determinants of Walking Speed in the Elderly.

BACKGROUND/AIMS: Walking speed (WS) is an objective measure of physical capacity and a modifiable risk factor of morbidity and mortality in the elderly. In this study, we (i) determined effects of 3-month supervised aerobic-strength training on WS, muscle strength, and habitual physical activity; (ii) evaluated capacity of long-term (21 months) training to sustain higher WS; and (iii) identified determinants of WS in the elderly. METHODS: Volunteers (F 48/M 14, 68.4 ± 7.1 years) completed either 3-month aerobic-strength (3 × 1 h/week, n = 48) or stretching (active control, n = 14) intervention (study A). Thirty-one individuals (F 24/M 7) from study A continued in supervised aerobic-strength training (2 × 1 h/week, 21 months) and 6 (F 5/M 1) became nonexercising controls. RESULTS: Three-month aerobic-strength training increased preferred and maximal WS (10-m walk test, p < 0.01), muscle strength (p < 0.01) and torque (p < 0.01) at knee extension, and 24-h habitual physical activity (p < 0.001), while stretching increased only preferred WS (p < 0.03). Effect of training on maximal WS was most prominent in individuals with baseline WS between 1.85 and 2.30 m·s-1. Maximal WS measured before intervention correlated negatively with age (r = -0.339, p = 0.007), but this correlation was weakened by the intervention (r = -0.238, p = 0.06). WS progressively increased within the first 9 months of aerobic-strength training (p < 0.001) and remained elevated during 21-month intervention (p < 0.01). Cerebellar gray matter volume (MRI) was positively associated with maximal (r = 0.54; p < 0.0001) but not preferred WS and explained >26% of its variability, while age had only minor effect. CONCLUSIONS: Supervised aerobic-strength training increased WS, strength, and dynamics of voluntary knee extension as well as habitual physical activity in older individuals. Favorable changes in WS were sustainable over the 21-month period by a lower dose of aerobic-strength training. Training effects on WS were not limited by age, and cerebellar cortex volume was the key determinant of WS.

Relation between testosterone levels and body composition, physical functioning and selected biochemical parameters in adult males.

INTRODUCTION: The objective of the study was to examine the relationship between the values of selected parameters of physical function, body composition, body mass index (BMI) and biochemical markers of metabolic health with the total testosterone (TT) levels in adult males. We aimed to analyse the correlation between these values and variations in the TT levels. METHODS: A total of 17 subjects (age = 50.2 ± 8.1 years, TT = 11.4 ± 3.8nmol/l) were included in the study. Subjects were tested on physical function (1RM on leg press, bench-press, handgrip, VO2max), body composition (DXA), biochemical parameters (morning fasting blood samples). RESULTS: TT was inversely correlated with abdominal circumference (AC) (p.

The effectiveness of two different multimodal training modes on physical performance in elderly.

The study compared the effect of 12-week multimodal training programme performed twice a week at the regular exercise facility (REF) with the 12-week multimodal training programme performed three times per week as a part of the research programme (EX). Additionally, the study analysed how the experimental training programme affect the physical performance of cognitive healthy and mild cognitive impaired elderly (MCI). The REF training group included 19 elderly (65.00±3.62 years). The experimental training programme combined cognitively healthy (EXH: n=16; 66.3±6.42 years) and age-matched individuals with MCI (EXMCI: n=14; 66.00±4.79 years). 10m maximal walking speed (10mMWS), Five Times Sit-to-Stand Test (FTSS), maximal and relative voluntary contraction (MVC & rel. MVC) were analysed. The REF group improved in 10mMWS (t=2.431, p=.026), the MVC (t=-3.528, p=.002) and relative MVC (t=3.553, p=.002). The EXH group improved in FTSS (t=5.210, P=.000), MVC (t=2.771, p=.018) and relative MVC (t=-3.793, p=.004). EXMCI improved in FTSS (t=2.936, p=.012) and MVC (t=-2.276, p=.040). According to results, both training programmes sufficiently improved walking speed and muscle strength in cognitively healthy elderly. Moreover, the experimental training programme improved muscle strength in MCI elderly.

Acute and regular exercise distinctly modulate serum, plasma and skeletal muscle BDNF in the elderly.

Brain-derived neurotrophic factor (BDNF) participates in orchestrating the adaptive response to exercise. However, the importance of transient changes in circulating BDNF for eliciting whole-body and skeletal muscle exercise benefits in humans remains relatively unexplored. Here, we investigated effects of acute aerobic exercise and 3-month aerobic-strength training on serum, plasma and skeletal muscle BDNF in twenty-two sedentary older individuals (69.0 ±â€¯8.0 yrs., 9 M/13F). BDNF response to acute exercise was additionally evaluated in young trained individuals (25.1 ±â€¯2.1 yrs., 3 M/5F). Acute aerobic exercise transiently increased serum BDNF in sedentary (16%, p = .007) but not in trained elderly or young individuals. Resting serum or plasma BDNF was not regulated by exercise training in the elderly. However, subtle training-related changes of serum BDNF positively correlated with improvements in walking speed (R = 0.59, p = .005), muscle mass (R = 0.43, p = .04) and cognitive performance (R = 0.41, p = .05) and negatively with changes in body fat (R = -0.43, p = .04) and triglyceridemia (R = -0.53, p = .01). Individuals who increased muscle BDNF protein in response to 3-month training (responders) displayed stronger acute exercise-induced increase in serum BDNF than non-responders (p = .006). In addition, muscle BDNF protein content positively correlated with type II-to-type I muscle fiber ratio (R = 0.587, p = .008) and with the rate of post-exercise muscle ATP re-synthesis (R = 0.703, p = .005). Contrary to serum, acute aerobic exercise resulted in a decline of plasma BDNF 1 h post-exercise in both elderly-trained (-34%, p = .002) and young-trained individuals (-48%, p = .034). Acute circulating BDNF regulation by exercise was dependent on the level of physical fitness and correlated with training-induced improvements in metabolic and cognitive functions. Our observations provide an indirect evidence that distinct exercise-induced changes in serum and plasma BDNF as well as training-related increase in muscle BDNF protein, paralleled by improvements in muscle and whole-body clinical phenotypes, are involved in the coordinated adaptive response to exercise in humans.

Strength training as a supplemental therapy for androgen deficiency of the aging male (ADAM): study protocol for a three-arm clinical trial.

INTRODUCTION: Androgen deficiency of the ageing male is a clinical syndrome resulting from the low production of androgens (testosterone levels <6.9 nmol/L) with symptoms including decline in lean mass, muscle strength, increases in body mass and overall fat mass. The aim of the study is to examine the effect of a 12 week strength training intervention on body composition, physical function, muscle cellular and molecular and selected biochemical markers of metabolic health in hypogonadal patients. METHODS AND ANALYSIS: The study is three-group controlled 12-week experiment to assess the effect of strength training on hypogonadal patients with testosterone replacement therapy and newly diagnosed males without testosterone replacement therapy. Age matched healthy eugonadal males are also engaged in strength training. Lean mass is used to determine sample size indicating, that 22 subjects per group will be sufficient to detect intervention related changes at the power of 0.90. All outcomes are collected before the intervention (pre-intervention assessments) and after the intervention (post-intervention assessments). Clinical outcomes are body composition (lean mass, fat mass and total body mass) measured by dual-energy X-ray absorptiometry, physical functioning assessed by physical tests and psychosocial functioning. The most important haematological and biochemical parameters included are glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, testosterone, luteinizing hormone, follicle-stimulating hormone, sexhormone-binding globulin, insulin and prostate-specific antigen. Muscle cellular and molecular outcomes are muscle fibre size and regulators of muscle fibre size. Muscle cellular outcomes are measured from muscle biopsies obtained from musculus vastus lateralis. ETHICS AND DISSEMINATION: This trial is approved by Ethics Committee of the University Hospital in Bratislava, Slovakia, (ref. trial number: 127/2017) and all subjects will be fully informed on the rationale, risks and benefits of the study and sign the written informed consent prior to entering the study. Results will be published in peer-reviewed journals and presented in scientific conferences. TRIAL REGISTRATION NUMBER: NCT03282682.

Acute effect of different concentrations of cayenne pepper cataplasm on sensory-motor functions and serum levels of inflammation-related biomarkers in healthy subjects.

Physical medicine therapies are often used in treating widespread musculoskeletal disorders, such as neck and low back pain. Herbal cataplasms containing rubefacient substances, such as Cayenne pepper, or galenic preparations like Munari cataplasm are commonly used as natural medications to treat painful areas. In this paper we show the effects of a 20-min application of Cayenne pepper and kaolin powder cataplasm (CPC) on healthy subjects. Treatment effects were evaluated by cold/hot feeling on visual analogue scale, blood pressure, body temperature, skin light touch sensations, two-point discrimination, and pain threshold to a mechanical stimulus, before and immediately after, 15 min after and 30 min after different concentration of Cayenne pepper in CPC preparation on healthy subjects. Maximal voluntary trunk extension force and trunk extension submaximal force matching error were also measured. In addition, the resulting optimal CPC mixture was tested for its safety by measuring changes in circulating levels of inflammatory-related biomarkers after 20-min application. The results indicate that the 5% concentration of Cayenne pepper in the preparation of CPC is the best choice, since no additional effects can be obtained with the 10% concentration, and the effects are higher than those observed at the 2.5% concentration. Importantly, 5% CPC application did not induce a significant increase of inflammatory-related biomarkers, suggesting that 20-min application has no negative side effects at systemic levels. Further studies are needed to investigate the immediate and long-term effects of repeated CPC applications as well as to understand the intersecting underlying mechanisms activated by Capsaicin and other identified factors, in order to be more extensively used in the field of physical medicine therapies.

Morphological, molecular and hormonal adaptations to early morning versus afternoon resistance training.

It has been clearly established that maximal force and power is lower in the morning compared to noon or afternoon hours. This morning neuromuscular deficit can be diminished by regularly training in the morning hours. However, there is limited and contradictory information upon hypertrophic adaptations to time-of-day-specific resistance training. Moreover, no cellular or molecular mechanisms related to muscle hypertrophy adaptation have been studied with this respect. Therefore, the present study examined effects of the time-of-day-specific resistance training on muscle hypertrophy, phosphorylation of selected proteins, hormonal concentrations and neuromuscular performance. Twenty five previously untrained males were randomly divided into a morning group (n = 11, age 23 ± 2 yrs), afternoon group (n = 7, 24 ± 4 yrs) and control group (n = 7, 24 ± 3 yrs). Both the morning and afternoon group underwent hypertrophy-type of resistance training with 22 training sessions over an 11-week period performed between 07:30-08:30 h and 16:00-17:00 h, respectively. Isometric MVC was tested before and immediately after an acute loading exclusively during their training times before and after the training period. Before acute loadings, resting blood samples were drawn and analysed for plasma testosterone and cortisol. At each testing occasion, muscle biopsies from m. vastus lateralis were obtained before and 60 min after the acute loading. Muscle specimens were analysed for muscle fibre cross-sectional areas (CSA) and for phosphorylated p70S6K, rpS6, p38MAPK, Erk1/2, and eEF2. In addition, the right quadriceps femoris was scanned with MRI before and after the training period. The control group underwent the same testing, except for MRI, between 11:00 h and 13:00 h but did not train. Voluntary muscle strength increased significantly in both the morning and afternoon training group by 16.9% and 15.2 %, respectively. Also muscle hypertrophy occurred by 8.8% and 11.9% (MRI, p < 0.001) and at muscle fibre CSA level by 21% and 18% (p < 0.01) in the morning and afternoon group, respectively. No significant changes were found in controls within these parameters. Both pre- and post-training acute loadings induced a significant (p < 0.001) reduction in muscle strength in all groups, not affected by time of day or training. The post-loading phosphorylation of p70S6Thr421/Ser424 increased independent of the time of day in the pre-training condition, whereas it was significantly increased in the morning group only after the training period (p < 0.05). Phosphorylation of rpS6 and p38MAPK increased acutely both before and after training in a time-of-day independent manner (p < 0.05 at all occasions). Phosphorylation of p70S6Thr389, eEF2 and Erk1/2 did not change at any time point. No statistically significant correlations were found between changes in muscle fibre CSA, MRI and cell signalling data. Resting testosterone was not statistically different among groups at any time point. Resting cortisol declined significantly from pre- to post-training in all three groups (p < 0.05). In conclusion, similar levels of muscle strength and hypertrophy could be achieved regardless of time of the day in previously untrained men. However, at the level of skeletal muscle signalling, the extent of adaptation in some parameters may be time of day dependent.

Aerobic-Strength Exercise Improves Metabolism and Clinical State in Parkinson's Disease Patients.

Regular exercise ameliorates motor symptoms in Parkinson's disease (PD). Here, we aimed to provide evidence that exercise brings additional benefits to the whole-body metabolism and skeletal muscle molecular and functional characteristics, which might help to explain exercise-induced improvements in the clinical state. 3-months supervised endurance/strength training was performed in early/mid-stage PD patients and age/gender-matched individuals (n = 11/11). The effects of exercise on resting energy expenditure (REE), glucose metabolism, adiposity, and muscle energy metabolism (31P-MRS) were evaluated and compared to non-exercising PD patients. Two muscle biopsies were taken to determine intervention-induced changes in fiber type, mitochondrial content, and expression of genes related to muscle energy metabolism, as well as proliferative and regenerative capacity. Exercise improved the clinical disability score (MDS-UPDRS), bradykinesia, balance, walking speed, REE, and glucose metabolism and increased muscle expression of energy sensors (AMPK). However, the exercise-induced increase in muscle mass/strength, mitochondrial content, type II fiber size, and postexercise phosphocreatine (PCr) recovery (31P-MRS) were found only in controls. Nevertheless, MDS-UPDRS was associated with muscle AMPK and mechano-growth factor (MGF) expression. Improvements in fasting glycemia were positively associated with muscle function and the expression of Sirt1 and Cox7a1, and the parameters of fitness/strength were positively associated with the expression of MyHC2, MyHC7, and MGF. Moreover, reduced bradykinesia was associated with better muscle metabolism (maximal oxidative capacity and postexercise PCr recovery; 31P-MRS). Exercise training improved the clinical state in early/mid-stage Parkinson's disease patients, including motor functions and whole-body metabolism. Although the adaptive response to exercise in PD was different from that of controls, exercise-induced improvements in the PD clinical state were associated with specific adaptive changes in muscle functional, metabolic, and molecular characteristics. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT02253732.

Effects of Leg-Press Training With Moderate Vibration on Muscle Strength, Pain, and Function After Total Knee Arthroplasty: A Randomized Controlled Trial.

OBJECTIVES: To examine the effects of a time-saving leg-press training program with moderate vibration on strength parameters, pain, and functional outcomes of patients after total knee arthroplasty (TKA) in comparison with functional physiotherapy. DESIGN: Randomized controlled trial. SETTING: Outpatient rehabilitation department at a university teaching hospital. PARTICIPANTS: Patients (N=55) with TKA were randomly allocated into 2 rehabilitation groups. INTERVENTIONS: Six weeks after TKA, participants either underwent isokinetic leg-press training combined with moderate vibration (n=26) of 15 minutes per session or functional physiotherapy (n=29) of 30 minutes per session. Both groups received therapy twice a week for a period of 6 weeks. Participants were evaluated at baseline (6wk after TKA) and after the 6-week rehabilitation program. MAIN OUTCOME MEASURES: The main outcome measure was maximal voluntary contraction (MVC) of the involved leg. Secondary outcome measures were pain assessed with a visual analog scale (VAS), range of motion, stair test, timed Up and Go test, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: Both groups showed statistically significant improvements in MVC of knee extensors measured on the knee dynamometer (leg-press group: from 0.8±.06 to 1±.09Nm/kg body weight [BW], physiotherapy group: from 0.7±.06 to 0.9±.06Nm/kg BW; P<.05) and in closed kinetic chain on the leg press (leg-press group: from 8.9±.77 to 10.3±1.06N/kg BW, physiotherapy group: from 6.7±.54 to 9.1±.70N/kg BW; P<.05) and in pain at rest (leg-press group: from 2±.36 to 1.3±.36 on the VAS, physiotherapy group: from 1.2±.28 to 1.1±.31; P<.05), WOMAC scores, and functional measurements after 6 weeks of training. There was no significant difference between the 2 groups concerning strength, pain, and functional outcomes after training (P>.05). CONCLUSIONS: Isokinetic leg-press training with moderate vibration and functional physiotherapy are both effective in regaining muscle strength and function after TKA; however, isokinetic leg-press training is considerably less time consuming.

Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics.

Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca2+ homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice. To understand the relevance of MCU-dependent mitochondrial Ca2+ uptake in aging and to investigate the effect of physical exercise on MCU expression and mitochondria dynamics, we analyzed skeletal muscle biopsies from 70-year-old subjects 9 weeks trained with either neuromuscular electrical stimulation (ES) or leg press. Here, we demonstrate that improved muscle function and structure induced by both trainings are linked to increased protein levels of MCU Ultrastructural analyses by electron microscopy showed remodeling of mitochondrial apparatus in ES-trained muscles that is consistent with an adaptation to physical exercise, a response likely mediated by an increased expression of mitochondrial fusion protein OPA1. Altogether these results indicate that the ES-dependent physiological effects on skeletal muscle size and force are associated with changes in mitochondrial-related proteins involved in Ca2+ homeostasis and mitochondrial shape. These original findings in aging human skeletal muscle confirm the data obtained in mice and propose MCU and mitochondria-related proteins as potential pharmacological targets to counteract age-related muscle loss.

Physical Exercise in Aging: Nine Weeks of Leg Press or Electrical Stimulation Training in 70 Years Old Sedentary Elderly People.

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.

Physical Activity in Elderly.

Aging is a multifactorial irreversible process associated with significant decline in muscle mass and neuromuscular functions. One of the most efficient methods to counteract age-related changes in muscle mass and function is physical exercise. An alternative effective intervention to improve muscle structure and performance is electrical stimulation. In the present work we present the positive effects of physical activity in elderly and a study where the effects of a 8-week period of functional electrical stimulation and strength training with proprioceptive stimulation in elderly are compared.

Electrical stimulation counteracts muscle decline in seniors.

The loss in muscle mass coupled with a decrease in specific force and shift in fiber composition are hallmarks of aging. Training and regular exercise attenuate the signs of sarcopenia. However, pathologic conditions limit the ability to perform physical exercise. We addressed whether electrical stimulation (ES) is an alternative intervention to improve muscle recovery and defined the molecular mechanism associated with improvement in muscle structure and function. We analyzed, at functional, structural, and molecular level, the effects of ES training on healthy seniors with normal life style, without routine sport activity. ES was able to improve muscle torque and functional performances of seniors and increased the size of fast muscle fibers. At molecular level, ES induced up-regulation of IGF-1 and modulation of MuRF-1, a muscle-specific atrophy-related gene. ES also induced up-regulation of relevant markers of differentiating satellite cells and of extracellular matrix remodeling, which might guarantee shape and mechanical forces of trained skeletal muscle as well as maintenance of satellite cell function, reducing fibrosis. Our data provide evidence that ES is a safe method to counteract muscle decline associated with aging.

Long-term high-level exercise promotes muscle reinnervation with age.

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.