Effect of age and sex on jumping mechanography and other measures of muscle mass and function

Objectives:

Sarcopenia increases falls and fracture risk. Sarcopenia clinical trials require robust quantitative tools to evaluate muscle function; jumping mechanography (JM) is likely one such tool. However, US data comparing JM with traditional tests across the lifespan is limited. This study evaluated the effect of age and sex on JM compared with traditional function tests and lean mass.

Methods:

US adults (213 women/119 men; mean age 65.4 years, range 27-96) performed functional tests including JM, Short Physical Performance Battery (SPPB) and grip strength (GS). Appendicular lean mass (ALM) was measured using DXA.

Results:

Men had higher relative jump power [mean (SD) 28.5 (10.52) vs. 21.9 (7.11) W/kg], GS [35.5 (9.84) vs. 22.7 (6.98) kg] and ALM/ht² [8.25 (1.35) vs. 6.99 (1.38) kg/m²] (all p<0.0001); no difference was observed for SPPB components. JM parameters were more strongly correlated with age than traditional tests (R²=0.38-0.61 vs. R²=0.01-0.28) and weakly with GS and chair rise time (R²=0.30-0.36).

Conclusion:

JM parameters are correlated with GS and chair rise time and demonstrate stronger correlations with age. JM shows promise as a valuable tool to evaluate and monitor interventions for sarcopenia as it could potentially detect change in muscle function more precisely than existing tools.     

Mechanography performance tests and their association with sarcopenia,falls and impairment in the activities of daily living – a pilot cross-sectional study in 293 older adults

Objectives:

Muscle mass and muscle power considerably decline with aging. The aim of the present study was to determine the association between muscular function using mechanography and sarcopenia, falls and impairment in the activities of daily living (ADL) in a sample of 293 community-dwelling women and men aged 60-85 years in Berlin, Germany.

Methods:

Muscle function was determined by muscle power per body mass in vertical countermovement jumps (2LJP_rel) and the chair rising test (CRTP_rel) on a force plate. Sarcopenia status was assessed by estimating appendicular muscle mass with dual-X-ray absorptiometry. Self-reported ADL impairment and falls in the last 12 months were determined.

Results:

ADL impairment was significantly correlated with all performance tests but not with muscle mass. The 2LJP_rel (OR 0.88, 95%-CI 0.79-0.98), the Esslinger Fitness Index (EFI) (OR 0.97, 95%-CI 0.94-1.00) and the maximal velocity of the CRT (OR 0.70, 95%-CI 0.53-0.93) remained significant correlates for sarcopenia independent of age in men but not in women. The EFI could differentiate female individuals who had past fall events (OR 0.96, 95%-CI 0.93-0.98).

Conclusion:

The results of the present study highlight the importance of assessing muscle power in older individuals as a relevant correlate for functional decline.     

Electrical muscle stimulation: Application and potential role in aging society

Neurodegenerative diseases and sarcopenia become more prevalent as individuals age and, therefore, represent a serious issue for the healthcare system. Several studies have reported the relationship between physical activity and reduced incidence of dementia or cognitive deterioration. Thus, exercise and strength training are most recommended treatments, but it is proving difficult to engage individuals to initiate exercise and strength training. Electrical muscle stimulation (EMS) may provide an alternative and more efficient solution. Although EMS has undergone a decline in use, mainly because of stimulation discomfort, new technologies allow painless application of strong contractions. Such activation can be applied in higher exercise dosages and more efficiently than people are likely to achieve with exercise. Unlike orderly recruitment of motor units (MUs) during low intensity voluntary exercise, EMS activates large fast-twitch MUs with glycolytic fibers preferentially and this could have benefit for prevention and treatment of diabetes and chronic diseases associated with muscle atrophy that ultimately lead to bed-ridden conditions. Recent evidence highlights the potential for EMS to make a major impact on these and other lifestyle related diseases and its role as a useful modality for orthopedic and cardiac rehabilitation. This paper will discuss the potential for EMS to break new ground in effective interventions in these frontiers of medical science.     

Determinants of muscle power and force as assessed by Jumping Mechanography in rural Indian children

Objectives:To: 1. Assess muscle function (MF) of rural Indian children (6-11y, n=232), using Jumping Mechanography (JM) and hand dynamometer, 2. Investigate gender differences, 3. Identify determinants of MF.Methods:Data on anthropometry, muscle mass%, diet, physical activity, sunlight exposure, MF (maximum relative power Pmax/mass, maximum relative force Fmax/BW by JM; relative grip strength (RGS) by hand dynamometer) were collected. Pearson’s correlation and hierarchical linear regression was performed.Results:Pmax/mass, Fmax/BW and RGS of the group were 31.7±5.0W/kg, 3.0±0.3 and 0.4±0.1 (mean±SD), respectively. The Pmax/mass Z-score was –1.1±0.9 and Fmax/BW Z-score was –0.9±1 (mean±SD) which was significantly lower than the machine reference data (p<0.05). Positive association of muscle mass% and protein intake was observed with all MF parameters and moderate+vigorous physical activity with Fmax/BW (p<0.05). Determinants of MF identified through regression for Pmax/mass were age (β=1.83,95% CI=0.973 – 2.686), muscle mass% (β=0.244,95% CI=0.131–0.358) and protein intake (β=3.211,95% CI=1.597–4.825) and for Fmax/BW was protein intake (β=0.130,95% CI=0.023–0.237) (p<0.05). Male gender was a positive predictor of having higher Pmax/mass (β=1.707,95% CI=0.040–3.373) (p<0.05).Conclusion:MF was lower than in western counterparts. To optimize MF of rural Indian children, focus should be on improving muscle mass, ensuring adequate dietary protein, and increasing physical activity, especially in girls.     

Intramuscular pressure of human tibialis anterior muscle detects age-related changes in muscle performance

Intramuscular pressure (IMP) reflects forces produced by a muscle. Age is one of the determinants of skeletal muscle performance. The present study aimed to test whether IMP mirrors known age-related muscular changes. We simultaneously measured the tibialis anterior (TA) IMP, compound muscle action potential (CMAP), and ankle torque in thirteen older adults (60–80 years old) in vivo by applying different stimulation intensities and frequencies. We found significant positive correlations between the stimulation intensity and IMP and CMAP. Increasing stimulation frequency caused ankle torque and IMP to increase. The electromechanical delay (EMD) (36 ms) was longer than the onset of IMP (IMPD) (29 ms). Compared to the previously published data collected from young adults (21–40 years old) in identical conditions, the TA CMAP and IMP of older adults at maximum intensity of stimulation were 23.8% and 39.6% lower, respectively. For different stimulation frequencies, CMAP, IMP, as well as ankle torque of older adults were 20.5%, 24.2%, and 13.2% lower, respectively. Surprisingly, the EMD did not exhibit any difference between young and older adults and the IMPD was consistent with the EMD. Data supporting the hypotheses suggest that IMP measurement is an indicator of muscle performance in older adults.     

Fat mass limits lower-extremity relative strength and maximal walking performance in older women

The purpose of this study was to determine if excess fat negatively affects relative strength and walking gait performance in overweight, older women. Twenty-five older women (65–80 yr) were separated into normal weight (BMI < 25 kg m⁻², n = 11) and overweight groups (BMI ? 25 kg m⁻², n = 14). Strength and rate of torque development (RTD) of the knee extensors and flexors, ankle plantarflexors and dorsiflexors were measured. Participants walked at standard and maximal speeds during which muscle activation, spatiotemporal and kinetic gait variables were measured. Relative to mass, overweight older women had 24% lower maximal torque and 38% lower RTD than normal weight women. Maximal walking speed was slower in overweight (1.25 ± 0.22 vs. 1.54 ± 0.25 m s⁻¹, P = 0.004) and was correlated to strength (r = 0.53, P < 0.01) and fat mass (r = −0.65, P = 0.001). At maximal speed, overweight had 11% lower vertical ground reaction force relative to mass, 8% slower stride rate, 12% shorter strides, 13% longer foot–ground contact times, 21% longer double-limb support times, 65% greater knee extensor and 78% greater plantarflexor activation (P < 0.05). Overweight, older women demonstrated altered gait and reduced walking performance related to poor relative strength and rate of torque development of lower-extremity muscles.     

Altered proteasome function and subunit composition in aged muscle

Myofibrillar protein degradation is mediated through the ubiquitin-proteasome pathway. To investigate if altered proteasome activity plays a role in age-related muscle atrophy, we examined muscle size and proteasome function in young and aged F344BN rats. Significant age-related muscle atrophy was confirmed by the 38% decrease in cross-sectional area of type 1 fibers in soleus muscle. Determination of proteasome function showed hydrolysis of fluorogenic peptides was equivalent between ages. However, when accounting for the 3-fold increase in content of the 20S catalytic core in aged muscle, the lower specific activity suggests a functional loss in individual proteins with aging. Comparing the composition of the catalytic beta-subunits showed an age-related 4-fold increase in the cytokine-inducible subunits, LMP2 and LMP7. Additionally, the content of the activating complexes, PA28 and PA700, relative to the 20S proteasome was reduced 50%. These results suggest significant alterations in the intrinsic activity, the percentage of immunoproteasome, and the regulation of the 20S proteasome by PA28 and PA700 in aged muscle.     

Specific protein changes contribute to the differential muscle mass loss during ageing

In the skeletal muscle, the ageing process is characterized by a loss of muscle mass and strength, coupled with a decline of mitochondrial function and a decrease of satellite cells. This profile is more pronounced in hindlimb than in forelimb muscles, both in humans and in rodents. Utilizing light and electron microscopy, myosin heavy chain isoform distribution, proteomic analysis by 2D‐DIGE, MALDI‐TOF MS and quantitative immunoblotting, this study analyzes the protein levels and the nuclear localization of specific molecules, which can contribute to a preferential muscle loss. Our results identify the molecular changes in the hindlimb (gastrocnemius) and forelimb (triceps) muscles during ageing in rats (3‐ and 22‐month‐old). Specifically, the oxidative metabolism contributes to tissue homeostasis in triceps, whereas respiratory chain disruption and oxidative‐stress‐induced damage imbalance the homeostasis in gastrocnemius muscle. High levels of dihydrolipoyllysine‐residue acetyltransferase (Dlat) and ATP synthase subunit alpha (Atp5a1) are detected in triceps and gastrocnemius, respectively. Interestingly, in triceps, both molecules are increased in the nucleus in aged rats and are associated to an increased protein acetylation and myoglobin availability. Furthermore, autophagy is retained in triceps whereas an enhanced fusion, decrement of mitophagy and of regenerative potential is observed in aged gastrocnemius muscle.     

Store-operated Ca2+ entry in muscle physiology and diseases

Ca²⁺ release from intracellular stores and influx from extracellular reservoir regulate a wide range of physiological functions including muscle contraction and rhythmic heartbeat. One of the most ubiquitous pathways involved in controlled Ca²⁺ influx into cells is store-operated Ca²⁺ entry (SOCE), which is activated by the reduction of Ca²⁺ concentration in the lumen of endoplasmic or sarcoplasmic reticulum (ER/SR). Although SOCE is pronounced in non-excitable cells, accumulating evidences highlight its presence and important roles in skeletal muscle and heart. Recent discovery of STIM proteins as ER/SR Ca²⁺ sensors and Orai proteins as Ca²⁺ channel pore forming unit expedited the mechanistic understanding of this pathway. This review focuses on current advances of SOCE components, regulation and physiologic and pathophysiologic roles in muscles. The specific property and the dysfunction of this pathway in muscle diseases, and new directions for future research in this rapidly growing field are discussed. [BMB Reports 2014; 47(2): 69-79]     

Calf muscle work and segment energy changes in human treadmill walking

The relation between changes in potential and kinetic energy in a seven-segment model of the human body and the work of m. triceps surae was investigated in four subjects walking on a treadmill at speeds between 0.5 and 2.0 m/s. Segment energy levels were determined by means of tachometers attached with strings to various points on the subject's body. Muscle work was assessed by electromyogram to force processing. M. triceps surae is active during stance, first doing negative (eccentric) work and ending with a short period of positive (concentric) work at “push-off”. It turned out that in normal walking these muscles provide the major part of positive work for the initiation of swing at push-off. Only at large step lengths, when push-off starts well before contralateral heel contact, is there a minor pushing forward of the trunk. In the negative work phase, m. triceps surae seem to check the forward speed of the trunk. A related decrease of trunk kinetic energy is not present, however, but this may be obscured by the simultaneous action of m. quadriceps femoris and, in a later stage, by a transfer of energy from the decelerating contralateral (swing) leg to the trunk. Energy of the trunk segment shows a sharp decline in double stance and a more gradual increase in the first half of single stance. Evidence is given that this effect is due to quadriceps action in the knee flexion-extension movement during stance. The presented results are incorporated in a general picture of energy flows in human walking.     

Effects of training and creatine supplement on muscle strength and body mass

The purpose of this study was to test the effect of creatine supplement on the size of the extra- and intracellular compartments and on the increase of isokinetic force during a strength training-program. Twenty-five healthy male subjects (age 22.0+/-2.9 years) participated in this experiment. Seven subjects formed the control-group. They did not complete any training and did not have any dietary supplement. The eighteen other subjects were randomly divided into a creatine- (n = 8) and a placebo-group (n = 10). They were submitted to a controlled strength-training program for 42 days followed by a detraining period of 21 days. Creatine and placebo were given over a period of 9 weeks. The size of the body water compartments was assessed by bioimpedance spectroscopy and the isokinetic force was determined during a single squat by means of an isokinetic dynamometer. These measurements were completed beforehand, at the end of the training period, and after the determining period. Both placebo- and creatine-group increased the isokinetic force by about 6% after the training period, showing that creatine ingestion does not induce a higher increase of the force measured during a single movement. No change in body mass was observed in the control- and placebo-groups during the entire experiment period while the body mass of the creatine-group was increased by 2 kg (P < 0.001). This change can be attributed partially to an increase (P = 0.039) in the body water content (+1.11), and more specifically, to an increase (P < 0.001) in the volume of the inter-cellular compartment (+0.61). Nevertheless, the relative volumes of the body water compartments remained constant and therefore the gain in body mass cannot be attributed to water retention, but probably to dry matter growth accompanied with a normal water volume.     

Peak power and body mass as predictors of tibial bone strength in healthy male and female adults

Objective:The purpose of this study was to examine whether a non-invasive, muscular fitness field test was a better predictor of bone strength compared to body mass in healthy adults.Methods:Hierarchical multiple regression analyses were used to determine the amount of variance that peak power explained for tibial bone strength compared to body mass. Peak power was estimated from maximal vertical jump height using the Sayer’s equation. Peripheral quantitative computed tomography scans were used to assess bone strength measures.Results:Peak power (β=0.541, p<0.001) contributed more to the unique variance in bone strength index for compression (trabecular bone) compared to body mass (β=-0.102, p=0.332). For polar strength strain index (cortical bone), the beta coefficient for body mass remained significant (β=0.257, p<0.006), however peak power’s contribution was similar (β=0.213, p=0.051).Conclusion:Compared to body mass, peak power was a better predictor for trabecular bone strength but similar to body mass for cortical bone strength. These data provide additional support for the development of a vertical jump test as an objective, valid and reliable measure to monitor bone strength among youth and adult populations.     

Inhibition of myostatin in adult mice increases skeletal muscle mass and strength

A human therapeutic that specifically modulates skeletal muscle growth would potentially provide a benefit for a variety of conditions including sarcopenia, cachexia, and muscular dystrophy. Myostatin, a member of the TGF-beta family of growth factors, is a known negative regulator of muscle mass, as mice lacking the myostatin gene have increased muscle mass. Thus, an inhibitor of myostatin may be useful therapeutically as an anabolic agent for muscle. However, since myostatin is expressed in both developing and adult muscles, it is not clear whether it regulates muscle mass during development or in adults. In order to test the hypothesis that myostatin regulates muscle mass in adults, we generated an inhibitory antibody to myostatin and administered it to adult mice. Here we show that mice treated pharmacologically with an antibody to myostatin have increased skeletal muscle mass and increased grip strength. These data show for the first time that myostatin acts postnatally as a negative regulator of skeletal muscle growth and suggest that myostatin inhibitors could provide a therapeutic benefit in diseases for which muscle mass is limiting.     

Death receptor-associated pro-apoptotic signaling in aged skeletal muscle

Tumor necrosis factor-alpha (TNF-α) is elevated in the serum as a result of aging and it promotes pro-apoptotic signaling upon binding to the type I TNF receptor. It is not known if activation of this apoptotic pathway contributes to the well-documented age-associated decline in muscle mass (i.e. sarcopenia). We tested the hypothesis that skeletal muscles from aged rodents would exhibit elevations in markers involved in the extrinsic apoptotic pathway when compared to muscles from young adult rodents, thereby contributing to an increased incidence of nuclear apoptosis in these muscles. The plantaris (fast) and soleus (slow) muscles were studied in young adult (5–7 mo, n=8) and aged (33 mo, n=8) Fischer₃₄₄ × Brown Norway rats. Muscles from aged rats were significantly smaller while exhibiting a greater incidence of apoptosis. Furthermore, muscles from aged rats had higher type I TNF receptor and Fas associated death domain protein (FADD) mRNA, protein contents for FADD, BCL-2 Interacting Domain (Bid), FLICE-inhibitory protein (FLIP), and enzymatic activities of caspase-8 and caspase-3 than muscles from young adult rats. Significant correlations were observed in the plantaris muscle between caspase activity and muscle weight and the apoptotic index, while similar relationships were not found in the soleus. These data demonstrate that pro-apoptotic signaling downstream of the TNF receptor is active in aged muscles. Furthermore, our data extend the previous demonstration that type II fibers are preferentially affected by aging and support the hypothesis that type II fiber containing skeletal muscles may be more susceptible to muscle mass loses via the extrinsic apoptotic pathway.     

Effect of resistance training to muscle failure vs non-failure on strength,hypertrophy and muscle architecture in trained individuals

The aim of this study was to compare the effects of resistance training to muscle failure (RT-F) and non-failure (RT-NF) on muscle mass, strength and activation of trained individuals. We also compared the effects of these protocols on muscle architecture parameters. A within-subjects design was used in which 14 participants had one leg randomly assigned to RT-F and the other to RT-NF. Each leg was trained 2 days per week for 10 weeks. Vastus lateralis (VL) muscle cross-sectional area (CSA), pennation angle (PA), fascicle length (FL) and 1-repetition maximum (1-RM) were assessed at baseline (Pre) and after 20 sessions (Post). The electromyographic signal (EMG) was assessed after the training period. RT-F and RT-NF protocols showed significant and similar increases in CSA (RT-F: 13.5% and RT-NF: 18.1%; P < 0.0001), PA (RT-F: 13.7% and RT-NF: 14.4%; P < 0.0001) and FL (RT-F: 11.8% and RT-NF: 8.6%; P < 0.0001). All protocols showed significant and similar increases in leg press (RT-F: 22.3% and RT-NF: 26.7%; P < 0.0001) and leg extension (RT-F: 33.3%, P < 0.0001 and RT-NF: 33.7%; P < 0.0001) 1-RM loads. No significant differences in EMG amplitude were detected between protocols (P > 0.05). In conclusion, RT-F and RT-NF are similarly effective in promoting increases in muscle mass, PA, FL, strength and activation.     

Body mass bias in a competition of muscle strength and aerobic power

Recently, a fitness competition called the Pump and Run (PR) has been popularized. Composed of 2 events, a 5-km road race time (RT) in seconds and a maximal-repetition bench press (BPR) with resistance based on a percentage of body mass (M), the final score (RTadj) equals RT - 30(BPR). From published findings, the authors hypothesized that the PR would impose a bias against heavier competitors. Furthermore, the potential for age bias in this event has not been evaluated. Therefore, the purpose of this study was to investigate M and age bias in the PR for men and women. For 74 female and 343 male competitors in a large PR event, RT, BPR, M, and age were collected from official competition results. Two subsamples were randomly created from the original sample: the validation (VAL) (54 women and 258 men) and the cross-validation (CVAL) (20 women and 85 men). For the VAL sample, the RTadj showed significant bias against heavier runners (women r = 0.35; men r = 0.28; P < 0.01 for both) but no age bias (women r = 0.04; men r = 0.005; P > 0.05 for both). Using allometric modeling, the authors developed a set of M-based correction factors to be multiplied by each RTadj to yield new adjusted run times (NRTadj) that would be free of M bias. As applied to the CVAL sample, the NRTadj values virtually eliminated the M bias (women r = 0.04; men r = 0.002; P > 0.05 for both) of the current PR scoring system and retained the absence of age bias (women r = 0.02; men r = 0.0002; P > 0.05 for both). The authors recommend the use of the NRTadj scores for future PR competitions.     

A new method for measuring power output in a single leg extension: feasibility, reliability and validity

A method is described for measuring the explosive power of the leg in extension which has been found safe and acceptable for all age groups and levels of physical capability. The extension movement takes 0.25-0.40 s in a push through 0.165 m against a flat pedal. At the end of the push the leg is fully extended. The movement is made seated so that the forces are contained between the buttocks and the foot. The seat position is adjusted for leg length and the push is transmitted by a lever and chain to spin a flywheel. The gearing is such that resistance to the movement remains velocity of the flywheel is measured by an optoswitch and used to calculated the average leg extensor power (LEP) in the push. The reliability of the power measurement was evaluated in 46 subjects ranging in age from 20 to 86 years; they included medical students and geriatric day patients. They were tested on two occasions separated by a week. The maximal values on the first occasion (best of at least five trials) ranged from 30 to 300 W (mean +/- 1 SD = 154 +/- 88 W). There was no significant difference on re-test and the coefficient of variation was 9.4%. In a subgroup of 9 non-naive subjects who were measured by an experienced observer it was 6.3%. As expected, power was lower in women than in men and declined sharply with age. The sex difference was less when the values were expressed as power per body mass; a sharp age-related decline remained.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peak anaerobic power in master athletes

The age-related decline in maximal physical performance of healthy subjects may be attributed both to the aging process per se and/or to a progressive reduction in physical activity. In two groups of master athletes, power (P) or endurance (E) trained (n = 115; aged 40-78 years), the degree and rate of the age-related deterioration of the maximal instantaneous muscle power (peak power, Wpeak), and the relative contribution of quantitative (muscle mass) and qualitative factors possibly underlying such deterioration were determined. Two groups of young athletes (n = 20; 17-26 years) and healthy untrained subjects (U, n = 37; 22-67 years) were also tested for comparison. The following two variables were assessed, firstly the lower limb muscle plus bone volume (LMV) by anthropometry, and secondly Wpeak, by means of a standardized vertical jump off both feet, performed on a force platform. The results obtained were that LMV of E and P, as well as of U, was about the same between age 20 and 45 years, whereas at older ages a progressive reduction was observed; the LMV values were higher in P than in E and U.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maximal aerobic power and leg muscle mass and strength related to age in non-athletic males and females

To investigate the relationships between the age-associated decline in peak oxygen uptake (peak VO2), leg muscle mass (LMM) and leg strength (LS) under the modulating effect of gender and level of physical activity (LPA, as assessed by questionnaire), we evaluated 71 sedentary subjects [males(M):females(F), 34:37], aged 20-80 years. Peak VO2 at maximum cycle ergometry was related to LMM (dual energy X-ray absorptiometry) and LS (isokinetic dynamometry) using both standard (y x x(-1)) and power function ratios (allometry). Absolute values of all variables were higher in males and declined with age (P < 0.01). Differences between the genders disappeared after peak VO2 x LS(-1.46(M)or -1.62(F)) adjustment but remained significant between peak VO2 LMM-(-0.51 (M)or -0.45(F)) and LS LMM- (-091(M) or -1.10(F)) corrected values. Allometric correction of peak VO2 and LS by LMM slowed their age-related declines; the flattening effect however, was more evident in the females. Interestingly, while no age-related decrement in peak VO2 LS(-1) was found, power function ratio values also declined with age, and at a slower rate in females. These findings are consistent with those obtained following a multiple regression analysis using LPA as an independent covariate (P < 0.01). We conclude that using adequate scaling methods and controlling by LPA: (1) no gender differences are observed in peak VO2 adjusted for LS, (2) loss of LS and LMM are important determinants of the age-associated reduction in physical fitness in both genders but (3) age per se has an LS- and LMM-independent influence on the functional decline, although this intrinsic effect of senescence is less pronounced in females.     

Mitochondrial death effectors: Relevance to sarcopenia and disuse muscle atrophy

Accelerated apoptosis in skeletal muscle is increasingly recognized as a potential mechanism contributing to the development of sarcopenia of aging and disuse muscle atrophy. Given their central role in the regulation of apoptosis, mitochondria are regarded as key players in the pathogenesis of myocyte loss during aging and other atrophying conditions. Oxidative damage to mitochondrial constituents, impaired respiration and altered mitochondrial turnover have been proposed as potential triggering events for mitochondrial apoptotic signaling. In addition, iron accumulation within mitochondria may enhance the susceptibility to apoptosis during the development of sarcopenia and possibly acute muscle atrophy, likely through exacerbation of oxidative stress. Mitochondria can induce myocyte apoptosis via both caspase-dependent and independent pathways, although the apoptogenic mediators involved may be different depending on age, muscle type and specific atrophying conditions. Despite the considerable advances made, additional research is necessary to establish a definite causal link between apoptotic signaling and the development of sarcopenia and acute atrophy. Furthermore, a translational effort is required to determine the role played by apoptosis in the pathogenesis of sarcopenia and disuse-induced muscle loss in human subjects.