A common definition of neuromuscular fatigue (NMF) is a reduction in maximal force or power capacities due to exercise. Fatigue can be more specifically defined as an activity-related circumstance in which there is a less than the expected or anticipated capacity to activate the motor pathway including muscles, for a given stimulus (1). In this sense, NMF is related to any progressive change in the supraspinal, spinal, or muscle properties during the course of intermittent or sustained exercise (1). The majority of studies have assessed the outcome of fatiguing tasks by evaluating voluntary isometric forces at various intensities (2). Yet, most tasks of daily living including exercise performance depend not only on torque or force generating capacity, but also are dependent on contractile velocity which, when combined with torque, determines power output. From the relatively few studies that have explored dynamic actions, it has become apparent that measurement of velocity and power responses to fatiguing tasks are important and can provide important additional information about neuromuscular function that has not been reflected from studies in isometric tasks. This may be especially important when exploring the central aspect of age-related changes in fatigability. For instance, Christie et al. (3) conducted a systematic review of the differences in muscle fatigability between young and old individuals and concluded that when isometric force was assessed after fatigue, most studies reported that older adults were able to maintain the force after fatigue better than or equal to younger individuals (3). However, only two studies had assessed power output after a fatiguing exercise when this study was published in 2011. Therefore, Christie et al. (3) argued that the low number of included studies in the review could have mitigated the strength of the results. In the last approximately 7 yr, nine studies in different muscle groups and using various dynamic tasks have been conducted with the purpose to understand how the age-related neuromuscular changes impair maximal power output capacity (4–12). This is important because an impaired ability to rapidly produce force during daily activities, such as rising from a chair or climbing stairs, can impact the ability to correct postural disturbances and avoid falls (13). Thus, a critical review of these recent studies on this topic is important and with the aim of guiding future studies in the field.
Not only different fatigue assessments (isometric force vs power output) but also different fatiguing tasks (isometric vs dynamic tasks) can influence NMF responses between old and young individuals. For instance, when both the fatiguing task and NMF measurements were performed in the isometric mode, the literature has usually reported a lower decrease in isometric force in older than younger subjects (12,14–21). However, the experimental works that have assessed fatigability isometrically after dynamic fatiguing tasks between old and young individuals have reported controversial results (4,5,8–11,22–25). Nonetheless, because of the relative simplicity of assessing isometric function versus dynamic function (power), isometric force measurements are frequently performed to assess NMF, even after dynamic task. The assessment of power output requires assessment of more variables using more complicated equipment, such as an isokinetic or isotonic dynamometers or customized instrumented ergometers, whereas isometric force can be quantified with more accessible and less expensive equipment.
The exercised muscle group (lower limbs vs upper limbs or extensors vs flexors) can also influence the magnitude of the age-related difference in NMF (3). This could be attributed to differences in neural patterning, fibre type (i.e., cross-sectional area occupied by type I vs type II fibers), muscle architecture and amount/type of habitual physical activity performed with the studied muscles (3). A recent study reported that age-related NMF is different when comparing knee extensors with elbow flexors muscle groups (24). Due to relatively greater changes in functional demands in the lower-limb muscles related to changes in lifestyle with aging, quadriceps (knee extensors) may demonstrate greater age-related neuromuscular remodelling than other muscle groups (26). Thus, several factors need to be explored and identified as studies advance toward dynamic tasks and fatigability with adult aging.
The primary purpose of this study was to systematically review the literature regarding the differences between old (>65 yr) and young (18–40 yr) people in NMF induced by isometric or dynamic tasks with a particular focus on the comparison between the type of fatigue measurement performed (isometric vs dynamic). That is, assessing isometric maximal voluntary contraction (IMVC) compared with power output and maximal velocity measured during dynamic contractions using a moderate resistance but one that can be concentrically moved repeatedly through a large range of joint motion. A systematic review of the proposed central and peripheral mechanisms contributing to the aetiology of age-related NMF will also be conducted as a secondary outcome. The second aim of this study was to examine whether the NMF differences between old and young individuals were similar for upper versus lower limb fatiguing contractions. In addition to differences in the fatiguing tasks, contraction mode (isometric vs dynamic) and muscle groups (upper limbs vs lower limbs), physical characteristics, such as sex, can also influence the NMF responses between young and older individuals. Recent works have shown that women are usually less fatigable than men (27,28), mainly when considering isometric tasks performed in the lower-limb muscles (21,24). Thus, the third aim of this meta-analysis was to investigate the effect of sex on age-related NMF. For the second and third objectives, fatigue induced by both isometric and dynamic contractions were considered but based on studies to date, only isometric measurement was reviewed as the main NMF outcome after each exercise modality.
This review included cross-sectional studies that compared the fatigue-induced responses of isometric force, velocity and power output between old (>65 yr) and young (18–40 yr) people. The following databases were searched: Medline (accessed via PubMed), EMBASE and Cochrane Central Register of Controlled Trials, and SPORT Discus. Searches were made in July of 2016 and updated in March 2017. The combination of terms related to the intervention (i.e., fatiguing exercise), population (old people) and outcomes (isometric force, velocity, and power output) were used. There was a language restriction (English) and the publication status had to be accepted or published. There was no restriction in terms of publication date. Details of the protocol and search strategy for this systematic review (see Document, Supplemental Digital Content 1, Search strategy, http://links.lww.com/MSS/B288) were registered on PROSPERO (CRD42016048389).
Selection of studies
The studies were selected by two independent authors (R.L.K. and S.J.A.). The initial screening consisted of title and abstract review. The inclusion criteria for studies in this first screening were as follows: 1) only human subjects research, that is, no animal or in vitro studies; 2) cross-sectional studies; 3) existence of an acute fatiguing exercise intervention, that is, any type of physical exercise that was performed with the purpose to induce fatigue; 4) fatigue assessed by isometric force, power output or maximal velocity; and 5) healthy subjects, that is, no clinical population. The exclusion criteria were as follows: 1) lack of a control group (young group); 2) no assessment of the main outcomes of interest in this review (i.e., isometric force, power output and/or maximal velocity); and 3) if old subjects were younger than 65 yr and/or if young participants were younger than 18 yr or older than 40 yr. If the abstracts did not provide enough information, an evaluation of the full text was performed by the same reviewers. Disagreements were solved by a third author (G.Y.M.).
Data were extracted independently by the same two authors (R.L.K. and S.J.A.). A standardized worksheet was provided for both authors to extract the following data: age, sample size, sex, fatiguing task, muscle group, relative isometric force decline, relative power output decrease, relative maximal velocity drop, reduction in electrically evoked forces amplitude and characteristics (i.e., contraction time [CT], half relaxation time [HRT], rate of force development and relaxation), compound muscle action potential (M-wave) properties and central activation parameters. Corresponding authors were contacted to provide missing data when there was a lack of information in their study. If the data were not provided by the authors, the study was not included in the systematic review. Because most of the studies routinely assess NMF using the conventional measurement tool (i.e., IMVC), six different meta-analyses were performed comparing relative changes in the isometric force (% of decrease from baseline measurement) between the old and young individuals, investigating NMF after/in (i) isometric fatiguing tasks, (ii) dynamic fatiguing tasks, (iii) upper limb exercise, (iv) lower limbs exercise, (v) male individuals, and (vi) female individuals. The seventh meta-analysis compared the relative change in power output after both dynamic and isometric fatiguing tasks between young and old individuals. Because relative changes in maximal velocity were reported in a small number of studies (n = 3), this outcome was not included in the analysis. Because inclusion of more than one data set from a given experiment could increase the likelihood of bias in overall effect size (ES) (29), only the highest velocity task was included for the power output meta-analysis when different velocities were assessed. Similarly, if any study reported different results for males and females, only results from males was included in the meta-analyses that did not aim to investigate the effect of sex on age-related NMF. Mean and standard deviation from prefatiguing to postfatiguing exercise in combination with sample size were used to calculate mean difference. When the postfatigue results were reported in a form of relative values (i.e., percentage of baseline), mean difference, the reported P-value and sample size were aggregated to compute the ES (Hedges g).
For the secondary outcomes (central and peripheral fatigue parameters), the following parameters were considered to examine peripheral fatigue: 1) Evoked forces amplitude including peak twitch (Pt), doublets, and tetanus amplitude; 2) Low-frequency fatigue (LFF), that is, the ratio of forces evoked at low over high-frequency stimulation; 3) Evoked force characteristics involved HRT (the time taken for tension to decline by 50% from peak twitch (Pt) or from force at the last pulse for tetanus), CT (time between the beginning of the contraction to the peak), rate of force relaxation (RFR) and rate of force development (RFD) (derivative of the force–time curve, expressed relative to peak force), maximal rate of force development (MRFD) (maximal slope of the force–time curve), and peak rate of relaxation (PRR) (steepest decline in torque during the EMG silence after stimulus); and 4) M-wave amplitude, area and/or duration, that is, EMG responses produced in response to a single stimulation.
To examine central fatigue, central activation parameters were extracted from the included studies: 1) Maximal voluntary activation (VA) quantified by dividing the amplitude of superimposed twitch (SIT) by the amplitude of an identical stimulation delivered in a relaxed muscle (i.e., VA peripheral nerve stimulation) or estimated resting twitch (i.e., VA transcranial magnetic stimulation, TMS); 2) SIT, that is, an evoked force induced by electrical or magnetic stimulation of peripheral nerve or cerebral cortex during the IMVC. If there was a lack of a good linear regression to determine estimated resting twitch, then SIT values were reported instead of VA. An increase in the SIT means a reduction in the central motor drive to the muscles; 3) Central activation ratio (CAR): CAR = IMVC force/(IMVC + superimposed tetanus); 4) maximal EMG signal normalized by M-wave (EMG/Mmax) which quantifies maximal central drive to the muscle; 5) TMS-induced motor evoked potentials (MEP) normalized by M-wave (MEP/Mmax) to assess corticospinal excitability; and 6) silent period: an inhibition period that follows the excitatory response to TMS.
The methodological quality assessment of all the included studies in the meta-analysis was performed with a modified Newcastle-Ottawa Quality Assessment Scale for cross-sectional studies. This scale has been modified from the Newcastle-Ottawa Quality Assessment Scale for cohort (30) to perform a quality assessment of cross-sectional studies for the systematic review (see Document, Supplemental Digital Content 2, Adapted “Newcastle - Ottawa Quality Assessment Scale,” http://links.lww.com/MSS/B289). This scale was a modified version of the “Newcastle-Ottawa Quality Assessment Scale” (NOS), as used by other studies (31,32). The following parameters were modified from the original scale: 1) the ascertainment of exposure was modified from risk factors in the original version to participants’ health status, because health status is an important inclusion criteria and needs to be similar between the two age groups; 2) for comparability, “physical activity status” was chosen as the most important confounding factor, because fatigue can be significantly influenced by subjects’ physical activity status (24,33); and 3) for the assessment of the main outcome (isometric force and/or power output decrease), the validity of the assessment tool used in the study (e.g., dynamometer, force transducer) was considered as the main factor. The NOS includes three categories (selection, comparability and outcome domains), with a maximum of nine points (stars).
Descriptive statistics (mean, median, and frequency) were used for quality assessment of all the included studies in the meta-analysis. Meta-analytic statistical comparisons were made with the Comprehensive Meta-analysis software V3 (BioStat Inc., Englewood, NJ). The Hedges g ES was calculated as a biased corrected standardized mean difference between the relative changes in isometric force and power output assessments between young and old individuals. The Hedges g ES and 95% confidence interval CI for the outcomes of each study is illustrated with forest plots (Figs. 1 to 4). The ES was calculated to evaluate the magnitude of the difference between young and old individuals according to the criterion of 0.80 large, 0.50 medium and 0.20 small (34). A positive ES indicates more fatigue in young people, whereas a negative ES represents greater fatigue in older individuals. The examination of interstudy heterogeneity was based on computing the weighted sum of squares [Q value] of the ES included in the meta-analysis. The difference of every ES from the combined ES (i.e., Hedges g ES in a random effect model) was calculated and squared. Then, the sum of the weighted squares was computed. The I2 and the P values (P < 0.05) were also considered to determine if the dispersion observed in the forest plot reflects difference in the true ES or random sampling error (29). Because heterogeneity was high (I2 > 50%), a random effect model was used to incorporate heterogeneity in meta-analyses (35). Publication bias was calculated based on the funnel plot method. The distribution of the estimated ES (Hedges g ES) for each study (on x-axis) and standard error (on y-axis) were used to calculate the measure. In this technique, the combined ES (and the corresponding CI) as well as the number of missing studies are calculated (36,37).
The electronic database searches provided a total of 11,003 articles. After removing the duplicates (n = 3098), 7905 abstracts were reviewed. After the first screening, 7809 studies were excluded because they did not meet the inclusion criteria. Thus, 96 studies (full texts) were assessed for eligibility. After this selection, 67 articles were excluded for the following reasons: (i) no assessment of the main outcomes of interest (n = 34); (ii) old subjects were younger than 65 yr (n = 24); (iii) same dataset (n = 1); and (iv) lack of information (n = 8). Thus, 29 studies met the inclusion criteria for the present systematic review. In the second search performed on March 2017, two more studies were included. Therefore, 31 studies were included in the meta-analysis (see Figure, Supplemental Digital Content 3, PRISMA Flow Diagram, http://links.lww.com/MSS/B290). Tables 1 and Table 2 describe the characteristics of the included studies divided by lower and upper limbs. Because of the large variety in outcome results’ presentation in the included studies, the relative changes (percent drop from baseline measurement) of the outcomes (isometric force and power output) after fatigue were calculated for the old and young individuals for each of the included studies.
Isometric force assessment
The first meta-analysis was conducted including studies that assessed isometric force changes when fatigue was induced by isometric tasks. Twenty studies met the criteria and were included in this meta-analysis (4,7,12,14–21,38–46). The meta-analysis revealed that isometric force loss was greater in young subjects when compared to their older counterparts (Hedges g ES, 0.913; CI, 0.435 to 1.391, P < 0.001) (Fig. 1). The test of Heterogeneity showed a significant value (Q value, 119.187; P < 0.001; I2 = 84.058) indicating that majority of the dispersion observed across studies could be due to parameters such as different populations, methods and responses of the subjects to various interventions used in the included studies, and not sampling error.
The second meta-analysis for the isometric force outcomes was conducted with fatigue induced by dynamic tasks. Eleven studies compared isometric force after a dynamic fatiguing task between old and young subjects (4,5,8–11,14,22–25). The overall effect from the meta-analysis showed no difference in the magnitude of isometric force between young and old adults (Hedges g ES, 0.322; CI, −0.039 to 0.682; P = 0.08) (Fig. 1). The heterogeneity was also high (Q value, 21.447; P = 0.018; I2 = 53.374), indicating that although the combined effect does not show any significance, the dispersion among studies observed effects could be due to parameters other than sampling error. Nineteen studies (7–12,14,16,19–25,40,43,44,46) were included in the third meta-analysis, which aimed to assess isometric force after fatiguing tasks in the lower limb muscle groups. Results indicated that young adults had a greater decline in isometric force when compared to their older counterparts (Hedges g ES, 0.948; CI, 0.463–1.433; P < 0.001) (Fig. 2). The heterogeneity test was also significantly high between ES derived from included studies (Q value, 113.658; P < 0.001; I2 = 84.163).
For the fourth meta-analysis which was conducted to analyze the effect of upper limb fatigue on isometric force, eleven studies were included (4,5,15,17,18,24,38,39,41,42,45). The analysis revealed no difference between young and old adults (Hedges g ES, 0.341; CI, −0.091–0.773; P = 0.122) (Fig. 2). The heterogeneity test was significantly high between ES derived from included studies (Q value, 26.768; P = 0.001; I2 = 65.239).
The fifth meta-analysis included eighteen studies that investigated the decrease in isometric force in males after a fatiguing exercise (4,5,7,9–11,16,17,19–22,24,25,39,41,42,44). These results showed young males had a greater loss in isometric force after fatiguing tasks when compared to their older counterparts (Hedges g ES, 0.538; CI, 0.174–0.901; P = 0.004) (Fig. 3). The heterogeneity test was significantly high between ES derived from included studies (Q value, 56.653; P < 0.001; I2 = 69.993).
Nine studies were included in the sixth meta-analysis, which aimed to assess isometric force decrease after a fatiguing task in females (5,8,12,17,19,21,23,24,41). Similarly, isometric force decline was greater in young females when compared to their older counterparts (Hedges g ES, 1.168; CI, 0.386–1.949; P = 0.003) (Fig. 3). The heterogeneity test was significantly high between ES derived from the included studies (Q value, 51.672; P < 0.001; I2 = 84.518).
Power output assessment
The seventh meta-analysis included eleven studies that assessed power output changes after fatigue induced by fatiguing exercises (4–12,20,47). Because only two studies used isometric tasks to induce fatigue (4,7), no separate analysis was performed for dynamic versus isometric task for this parameter. The overall effect indicates that older individuals demonstrate a greater reduction in power output after a fatiguing task (Hedges g ES, −0.891; CI, −1.657 to −0.125; P = 0.023) (Fig. 4). The heterogeneity test was also significantly high between ES derived from included studies (Q value, 78.175; P < 0.001; I2 = 87.208).
Only three studies (6,11,24) reported velocity changes between young and old adults after fatigue induced by physical exercise. Results were either nonsignificant (11) or old adults showed a higher decrease after fatigue (6,24).
Descriptive statistics were used to assess the quality of the studies. The mean of points (stars) of the included studies as 4.68 and the median was 4. The frequency of ratings is presented in a table in the supplemental digital content 4 (see Table, Supplemental Digital Content 4, Quality assessment, http://links.lww.com/MSS/B291). Regarding the risk of bias in the selection domain, 13% of the studies were classified as “good,” whereas 19% were classified as “fair” and 68% had a “poor” grade. For the risk of bias in the comparability domain, 6% of the included studies were classified as “good,” 72% were graded as “fair,” and 22% were “poor.” Finally, for the outcome domain, 94% of the studies were classified as “good” and just 6% of the studies were “poor.”
The ES of the included studies was plotted against the standard error for each of the seven meta-analysis (see Figures, Supplemental Digital Content 5, Funnel plots, http://links.lww.com/MSS/B292). There was no evidence of asymmetry in any of the funnel plots, indicating a considerably equal distribution of the studies along the horizontal line (Hedges g). The results of trim-and-fill analysis (36,37) revealed that there were no missing studies. The estimates of the effect of the missing studies were similar to the meta-analysis combined ES, suggesting a little chance of publication bias for these measures.
The secondary outcomes from the included studies are presented in Supplemental Digital Content 5 (see Figures, Supplemental Digital Content 5, Funnel plots, http://links.lww.com/MSS/B292). This table presents the difference in relative changes with fatigue between old and young individuals. Most of the included studies reported Pt amplitude changes with fatigue. Nine studies did not find any difference in Pt amplitude after fatigue between young and old individuals (9,10,16,17,19,25,38,39,45). Three studies reported that Pt amplitude decreased more after fatigue for young adults (11,18,38), whereas two other studies reported the opposite result (8,22). Nine experiments analyzed doublets and tetanus amplitude in response to fatigue (8,11,14–16,19–21,39). There was either no difference in the changes of the evoked force between young and old people (8,14,16,19,20,39) or younger individuals demonstrated a greater decrease in tetanic force (11,14,15,20,21). Two studies reported no difference in LFF between groups after fatigue (16,39), whereas LFF was greater in older adults in one study (8).
Regarding evoked forces properties, most of the studies showed no difference in HRT and CT responses between the age groups after fatigue (8,11,15–17,19,25,39). Three studies reported that HRT was lower for younger adults after a dynamic fatiguing task (9,10,22), which means that HRT was longer in older subjects in response to fatigue. However, three other studies reported the opposite result for HRT (16,20,21). For CT, only two studies reported a longer CT after a fatiguing task for older individuals (i.e., CT increased less for young individuals at the end of the fatiguing task) (9,22). Most of the included studies reported no significant difference in MRFD, RFD, RFR, and PRR between young and old individuals (4,5,16,17,19,25,45). Two studies reported a greater decrease in RFD and MRFD for older adults (6,8), whereas one experiment showed a higher drop in RFD (20) and lower PRR for younger individuals at the end of the fatiguing task (18). Likewise, most of the included studies reported no effect on M-wave properties (4,5,8,9,15–17,19,20,22,25,45). Two studies reported a greater decrease in M-wave amplitude after fatigue in younger individuals (16,39), whereas one study showed a larger decline in M-wave amplitude in elderlies (10). Despite having used different techniques to assess central drive, studies usually show no difference in central activation changes between old and young adults in response to a fatiguing task (4,5,8–11,14,16–20,22,39). Yet, central activation changes were more pronounced in older adults in three studies (38,45,46), but was further decreased in young individuals in three others (15,21,25).
The first aim of this meta-analysis was to systematically review the effect of exercise-induced NMF on isometric force and power output decreases between old (>65 yr) and young (18–40 yr) individuals. The main results from the meta-analyses indicate that younger individuals demonstrate a greater isometric force decline after an isometric fatiguing task. However, when power output was assessed after fatigue induced by either dynamic or isometric tasks, older subjects presented with a greater reduction in power output compared to young individuals. Furthermore, and not previously examined, this review identified no difference in the subsequent isometric force changes between young and old people when fatigue was induced by dynamic tasks. Analyses of upper compared with lower limb muscle groups highlighted that the decrease in isometric force after fatiguing tasks is muscle group dependent, that is, young adults exhibited a greater isometric force decrease after fatigue induced in the lower limbs but not in the upper limbs, meaning there is no age difference in fatigue in the upper limbs. Moreover, the age-related NMF fatigue difference between young and old individuals was not found to be sex-dependent, meaning that both old women’s and old men’s fatigue are equal but more than their younger counterparts.
The results of the meta-analysis indicate that isometric force decline is greater in young people after fatigue induced by isometric contractions. Among the 20 included studies in this meta-analysis, there was no difference in the isometric force changes between young and old individuals in 10 studies (4,7,39–46). However, despite the nonsignificant difference between groups, ES was moderate in favor of a greater fatigue in young subjects in at least 4 of these 10 studies (7,39,40,46). Contrary to what occurs after isometric fatiguing tasks, the results of the meta-analysis showed no difference in isometric force changes between age groups after a dynamic fatiguing tasks. This is a new interpretation that was not reported in a prior analysis (3). In the current review, based on the rationale that different measurements of fatigue can provide distinct information about the age-related NMF, we considered only isometric force decline, rather than combining isometric and dynamic assessments of fatigue in one meta-analysis (3).
The greater loss in isometric force in younger adults is in line with their larger decrease in tetanic force (14,15,20,21) and greater elongation in HRT (20,21) compared with older adults. Therefore, muscle contractile properties were also more affected in young compared with older adults after isometric fatiguing tasks. There are a few plausible explanations related to the aging process that explain why older individuals are more fatigue-resistant mainly during maximal and submaximal isometric contractions than younger individuals. First, the age-related motor unit (MU) remodelling process that involves collateral reinnervation of denervated fibres leads to an overall greater myosin heavy chain (MHC) coexpression in the skeletal muscle fiber population (48). More specifically, this process results in an increase in the number of fibers coexpressing MHC I and IIa, but the majority seems to be MHC I expression dominant fibers (17–19,44,49,50). The reduction in the number of fibers expressing MHC IIx in combination with fiber atrophy plays an important role in decreasing the glycolytic flux in older individuals, resulting in lower rates of glycolytic ATP production in comparison to younger adults; thus, older individuals likely rely more on oxidative sources (44). Ultimately, the greater involvement of oxidative phosphorylation results in lower acidosis and metabolite (e.g., inorganic phosphate) accumulation during sustained contraction than younger individuals, contributing to a greater fatigue resistance in older adults (44). It is important to note that this idea of a preferential shift to slow MHC expression is not always reported (51,52), and indeed one study reported a decrease in the percentage of type I fibers in nine elderly subjects from their sixth to seventh decade of life (52). These somewhat disparate findings however may not be a significant factor when muscle atrophy becomes more severe in very old muscles (>80 yr) (51).
Second, it is also expected that young adults are stronger than older adults. During high-intensity sustained isometric contractions, stronger muscles may generate higher intramuscular pressure, which can decrease oxygen delivery due to muscle ischemia, and consequently, increase metabolite concentrations (44). Third, recent evidence indicates that older individuals have a metabolic reserve in the skeletal muscle despite the advanced age and poorer physical status (53). Indeed, Layec et al. (53) reported an enhanced oxygen supply after blood occlusion in age adults, suggesting a preserved skeletal muscle metabolic reserve. Therefore, after sustained isometric contractions, which generate blood occlusion due to increased intramuscular pressure, muscle from age individuals are more resistant to fatigue because of their ability to reoxygenate tissue and capacity of improving mitochondrial ATP synthesis rate (53). Finally, previous studies have shown that older individuals have a greater metabolic economy also due to a lower MU firing rates (38,42,54,55). Lower firing rates require less energy (ATP) during a sustained task (42,56). However, it should be noted that age-related reductions in maximal MU firing rates is muscle-dependent (57) and that some muscles show minimal to modest reductions in firing rates (58,59). Overall, it seems reasonable that a lower metabolite (e.g., Pi, H+) accumulation combined perhaps with a lower MU firing rates contributes to a greater fatigue resistance in older subjects during sustained and maximal isometric contractions.
The results of our meta-analysis showed that reduction in power output was greater in older individuals than younger individuals. Some of the secondary outcomes reported in the included studies may explain possible age-related mechanisms that are involved in the greater power output reduction after fatigue in older individuals. For instance, a few studies report a prolongation in the HRT after high-velocity tasks in older subjects (9,10), but not after isometric fatiguing tasks (16,17,19,21,39). The longer muscle relaxation time after high-intensity dynamic tasks is usually accompanied by a greater reduction in power output in old subjects, suggesting a common fatigue mechanism between these two variables (9,11). This mechanism could be related to a slower cross-bridge cycle (actin and myosin attachment and detachment rate) and greater proportion of cross bridges remaining in the low force state with fatigue (60). Similarly, studies involving high-intensity dynamic fatiguing tasks have reported a greater reduction in RFD in older individuals after fatigue (6,8). A recent study showed that the decrease in RFD is associated with a lower neuromuscular activation level after fatigue, which could be explained by an age-related decrease in maximal MU firing rates (6), although these have not been recorded directly during dynamic fatiguing tasks. Therefore, alongside the changes in mechanical machinery of the exercised muscles, the magnitude of central motor output could be another major contributing factor in the decrease in RFD and maximal power output in older individuals. However, it is worth noting that the pattern of central fatigue changes in older adults is inconsistent possibly because different techniques (i.e., VA, CAR, SIT, MEP/Mmax, and EMG/Max—see Table, Supplemental Digital Content 6, Secondary outcomes, http://links.lww.com/MSS/B293) were used to assess central activation in the included studies, which might have affected the results. Most of the studies did not report any difference in the changes of evoked forces (Pts, doublets, and tetanus amplitudes) and M-wave amplitudes after fatigue between young and old people, despite various contraction modes, duty cycles, intensities and durations of the task. For this reason, it seems that these variables do not contribute to discrimination of fatigue aetiology between young and old people.
Interestingly, some of the studies that reported a greater decline in power output in older adults after fatigue (8–10) either did not find any difference in the magnitude of isometric force loss between young and old individuals or older adults were less fatigable when assessed with isometric force. These results indicate that the assessment of isometric force alone may not provide sufficient or useful information about fatigue responses between old and young individuals. That is, the assessment of power output is important because it is related to the ability to produce maximal velocity, which is highly affected negatively with aging (6,9,10,12,24). For instance, Wallace et al. (6) showed that the decrease in power output after fatigue was strongly associated with the decrease in velocity (r = 0.94). In addition, the correlation was greater between the decrease in the rate of velocity development, which is a measure of acceleration, and power output (r = 0.94) than for other torque-dependent variables, such as torque and RFD (0.81–0.87) (6). Therefore, the reduced capacity to rapidly accelerate a limb is a key factor that affects the ability of older adults to achieve maximal power output after fatigue, and it is probably related to the slower rate and time for cross-bridge cycle attachment with aging (6).
Isometric NMF induced in the upper versus lower limbs
Another novel finding of the present article is that NMF can be influenced by the muscle group exercised. Isometric force decline is lower in older individuals when NMF is tested in lower limb muscles, but not in upper limb muscle. This is in agreement with one recent study that directly addressed this issue and reported that the age-related difference in the magnitude of fatigability is greater in the lower limbs than in the upper limbs (24). The mechanism(s) that contributes to a difference in the fatigability in the upper and lower limbs between old and young individuals is not clear. It was speculated that age differences in MU activation, anatomy and contractile function may play a role (24). For instance, a relatively greater variability in the rate of sarcopenia is usually observed in the lower limbs muscles of aging populations due perhaps to disuse, compared to upper limb muscles (61). Sarcopenia is associated with a decrease in muscle cross-sectional area due to an age-related reduction in fiber number in combination with preferential atrophy of type II fibers (62). This age-related MU remodeling increases the ratio of type I:II area, which could improve the ability to maintain isometric force in older individuals (12,14,19). Regarding the upper-limb muscle groups, the P value was not significant for isometric force decrease and ES was low-to-moderate in favor of greater isometric force reduction in the younger group. Only 11 studies were included in the meta-analysis involving upper limb fatigue and, in most of these studies, fatigue was induced by isometric contractions either at 20% or 60% of the elbow flexors IMVC (4,5,18,24,38,41,42,45). Moreover, in only two studies was fatigue induced by a dynamic fatiguing task (5,24). Therefore, although NMF induced by exercise (isometric and dynamic combined) is greater in the lower limbs in younger individuals when fatigability is defined as a loss in isometric torque, more studies are needed to understand whether the etiology of age-related fatigability is different between upper and lower limb muscle groups.
Effects of sex on age-related isometric NMF
The meta-analyses results revealed that both old males and old females are more fatigue resistant than their younger counterparts when the isometric force decline is the main outcome measure. It is important to acknowledge that a limited number of experimental works have exclusively explored fatigue responses in old versus young females (8,12,23) in comparison with the far greater number of articles that have assessed fatigability in men (4,7,9–11,16,20,22,25,39,42,44). In addition, only a small number of studies have investigated the effect of sex on age-related NMF (5,17,19,21,24,41). Among these studies, three have shown that this age-related NMF difference between young and old individuals is larger in males than females (17,21,24). The greater relative area occupied by of slow oxidative muscle fibers and the lower initial force (muscle mass) in old adults (17,21) and females (28) may partly explain these sex and age differences. These conclusions are based on a relatively few studies and again more are needed to address comprehensively whether there is a sex difference.
This study has a few limitations: 1) Eight studies could not be included in the meta-analysis because of the lack of information and their inclusion could have altered the results of our meta-analysis. 2) Whereas it is known that fatigue is task specific, we combined studies in which fatigue was induced by different exercise tasks, such as different contraction mode, duty cycle, intensity and duration. 3) Only a few studies assessed fatigue in elderly subjects older than 75 yr (6,10,11,39,43,44,47). Previous studies have suggested that the decrease in muscle function is further accelerated with advanced age (>75 yr) (48). Thus, even though we combined all the elderly subjects in the same group for the meta-analyses, it is important to consider that younger old individuals (~65 yr) may show different responses than those over 75 yr of age (48). 4) Most of the included studies had a poor methodological quality in the selection and comparability domains. For instance, health and physical activity status in some studies was often not clear and adjusting for this important factor might affect the results.
The inclusion of seven recent articles on age-related fatigability confirm the main findings of a prior similar analyses on this topic, however the present review has provided several novel key findings. First, it is important to update a review on this topic with emerging studies especially those that are focused on dynamic actions which may be more applicable to everyday life. Thus, as noted previously (3) for isometric fatiguing tasks, older adults are less fatigable (i.e., have a better ability to maintain isometric force) than younger individuals in the lower limbs, but not in the upper limbs. However, specific new insights from this review are a lack of difference in the subsequent isometric force loss between young and old people when fatigue is induced by dynamic tasks and the more pronounced decrease in maximal power output after fatigue induced by both isometric and dynamic tasks in older adults. Furthermore, central and peripheral mechanisms contributing to the etiology of fatigue were examined to help understand the greater age-related decrease in power output. Among the factors that could potentially impact power output production after fatigue in old individuals are longer muscle relaxation time and decrease in rate of force development, likely due partly to decreased neuromuscular activation as well as structural and functional changes in the muscle with aging. Therefore, the assessment of fatigue (isometric force vs power output) must be considered in identifying age-related NMF differences between young and old individuals. Lastly, this meta-analysis showed that age-related muscle fatigue difference between young and old individuals is not sex-dependent.
R. L. K. is currently being sponsored by Brazilian National Research Council (CNPq/Brazil). S. J. A. is funded by an Eyes High Postdoctoral Fellowship from the University of Calgary. For the remaining authors, none were declared. The results are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and do not constitute endorsement by the American College of Sports Medicine.
Conflicts of Interest: The authors have no conflict of interest in relation to the present scientific article.
1. MacIntosh BR, Rassier DE. What is fatigue? Can J Appl Physiol
2. Twomey R, Aboodarda SJ, Kruger R, Culos-Reed SN, Temesi J, Millet GY. Neuromuscular fatigue during exercise: Methodological considerations, etiology and potential role in chronic fatigue. Neurophysiol Clin
3. Christie A, Snook EM, Kent-Braun JA. Systematic review and meta-analysis of skeletal muscle fatigue in old age. Med Sci Sports Exerc
4. Yoon T, Schlinder-Delap B, Hunter SK. Fatigability and recovery of arm muscles with advanced age for dynamic and isometric contractions. Exp Gerontol
5. Yoon T, Doyel R, Widule C, Hunter SK. Sex differences with aging in the fatigability of dynamic contractions. Exp Gerontol
6. Wallace JW, Power GA, Rice CL, Dalton BH. Time-dependent neuromuscular parameters in the plantar flexors support greater fatigability of old compared with younger males. Exp Gerontol
7. Thompson BJ, Conchola EC, Stock MS. Effects of age and muscle action type on acute strength and power recovery following fatigue of the leg flexors. Age (Dordr)
8. Power GA, Dalton BH, Rice CL, Vandervoort AA. Power loss is greater following lengthening contractions in old versus young women. Age (Dordr)
9. Dalton BH, Power GA, Vandervoort AA, Rice CL. The age-related slowing of voluntary shortening velocity exacerbates power loss during repeated fast knee extensions. Exp Gerontol
10. Dalton BH, Power GA, Vandervoort AA, Rice CL. Power loss is greater in old men than young men during fast plantar flexion contractions. J Appl Physiol (1985)
11. Dalton BH, Power GA, Paturel JR, Rice CL. Older men are more fatigable than young when matched for maximal power and knee extension angular velocity is unconstrained. Age (Dordr)
12. Callahan DM, Kent-Braun JA. Effect of old age on human skeletal muscle force–velocity and fatigue properties. J Appl Physiol (1985)
13. Casas-Herrero A, Cadore EL, Zambom-Ferraresi F, et al. Functional capacity, muscle fat infiltration, power output
, and cognitive impairment in institutionalized frail oldest old. Rejuvenation Res
14. Callahan DM, Foulis SA, Kent-Braun JA. Age-related fatigue resistance in the knee extensor muscles is specific to contraction mode. Muscle Nerve
15. Chan KM, Raja AJ, Strohschein FJ, Lechelt K. Age-related changes in muscle fatigue resistance in humans. Can J Neurol Sci
16. Chung LH, Callahan DM, Kent-Braun JA. Age-related resistance to skeletal muscle fatigue is preserved during ischemia. J Appl Physiol (1985)
17. Ditor DS, Hicks AL. The effect of age and gender on the relative fatigability of the human adductor pollicis muscle. Can J Physiol Pharmacol
18. Hunter SK, Todd G, Butler JE, Gandevia SC, Taylor JL. Recovery from supraspinal fatigue is slowed in old adults after fatiguing maximal isometric contractions. J Appl Physiol (1985)
19. Kent-Braun JA, Ng AV, Doyle JW, Towse TF. Human skeletal muscle responses vary with age and gender during fatigue due to incremental isometric exercise. J Appl Physiol (1985)
20. Lanza IR, Russ DW, Kent-Braun JA. Age-related enhancement of fatigue resistance is evident in men during both isometric and dynamic tasks. J Appl Physiol (1985)
21. Solianik R, Kreivenaite L, Streckis V, Mickeviciene D, Skurvydas A. Effects of age and sex on fatigability and recovery from a sustained maximal isometric voluntary contraction. J Electromyography Kinesiol
22. Bieuzen F, Hausswirth C, Louis J, Brisswalter J. Age-related changes in neuromuscular function and performance following a high-intensity intermittent task in endurance-trained men. Gerontology
23. Hakkinen K. Neuromuscular fatigue and recovery in women at different ages during heavy resistance loading. Electromyogr Clin Neurophysiol
24. Senefeld J, Yoon T, Hunter SK. Age differences in dynamic fatigability and variability of arm and leg muscles: Associations with physical function. Exp Gerontol
. 2017;87(Pt A):74–83.
25. Walker S, Peltonen H, Avela J, Hakkinen K. Neuromuscular fatigue in young and older men using constant or variable resistance. Eur J Appl Physiol
26. Piasecki M, Ireland A, Jones DA, McPhee JS. Age-dependent motor unit remodelling in human limb muscles. Biogerontology
27. Hunter SK. Sex differences in fatigability of dynamic contractions. Exp Physiol
28. Hunter SK. Sex differences in human fatigability: mechanisms and insight to physiological responses. Acta Physiol (Oxf)
29. Borenstein M, Hedges LV, Higgins P, Rothstein HR. Introduction to Meta-Analysis. Wiley Publishers; 2009. p. 102.
30. Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analysis. 2011. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
31. Grimes CA, Bolhuis DP, He FJ, Nowson CA. Dietary sodium intake and overweight and obesity in children and adults: a protocol for a systematic review and meta-analysis. Syst Rev
32. Herzog R, Alvarez-Pasquin MJ, Diaz C, Del Barrio JL, Estrada JM, Gil A. Are healthcare workers' intentions to vaccinate related to their knowledge, beliefs and attitudes? A systematic review. BMC Public Health
33. Power GA, Dalton BH, Behm DG, Vandervoort AA, Doherty TJ, Rice CL. Motor unit number estimates in masters runners: use it or lose it? Med Sci Sports Exerc
34. Cohen J. Statistical Power Analysis for the Behavioral Sciences
. 2nd ed. Hillsdale (NJ): Lawrence Erlbaum Associates; 1988. pp. 28–64.
35. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ
36. Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics
37. Duval S, Tweedie R. A nonparametric “Trim and Fill” method of accounting for publication bias in meta-analysis. J Am Stat Assoc
38. Yoon T, De-Lap BS, Griffith EE, Hunter SK. Age-related muscle fatigue after a low-force fatiguing contraction is explained by central fatigue. Muscle Nerve
39. Allman BL, Rice CL. Incomplete recovery of voluntary isometric force after fatigue is not affected by old age. Muscle Nerve
40. Griffith EE, Yoon T, Hunter SK. Age and load compliance alter time to task failure for a submaximal fatiguing contraction with the lower leg. J Appl Physiol (1985)
41. Hunter SK, Duchateau J, Enoka RM. Muscle fatigue and the mechanisms of task failure. Exerc Sport Sci Rev
42. Hunter SK, Rochette L, Critchlow A, Enoka RM. Time to task failure differs with load type when old adults perform a submaximal fatiguing contraction. Muscle Nerve
43. Justice JN, Mani D, Pierpoint LA, Enoka RM. Fatigability of the dorsiflexors and associations among multiple domains of motor function in young and old adults. Exp Gerontol
44. Lanza IR, Befroy DE, Kent-Braun JA. Age-related changes in ATP-producing pathways in human skeletal muscle in vivo. J Appl Physiol (1985)
45. Yoon T, Schlinder-Delap B, Keller ML, Hunter SK. Supraspinal fatigue impedes recovery from a low-intensity sustained contraction in old adults. J Appl Physiol (1985)
46. Stackhouse SK, Stevens JE, Lee SC, Pearce KM, Snyder-Mackler L, Binder-Macleod SA. Maximum voluntary activation in nonfatigued and fatigued muscle of young and elderly individuals. Phys Ther
47. McNeil CJ, Rice CL. Fatigability is increased with age during velocity-dependent contractions of the dorsiflexors. J Gerontol
48. Hepple RT, Rice CL. Innervation and neuromuscular control in ageing skeletal muscle. J Physiol
49. Andersen JL, Terzis G, Kryger A. Increase in the degree of coexpression of myosin heavy chain isoforms in skeletal muscle fibers of the very old. Muscle Nerve
50. Campbell MJ, McComas AJ, Petito F. Physiological changes in ageing muscles. J Neurol Neurosurg Psychiatry
51. Purves-Smith FM, Sgarioto N, Hepple RT. Fiber typing in aging muscle. Exerc Sport Sci Rev
52. Frontera WR, Hughes VA, Fielding RA, Fiatarone MA, Evans WJ, Roubenoff R. Aging of skeletal muscle: a 12-yr longitudinal study. J Appl Physiol (1985)
53. Layec G, Trinity JD, Hart CR, et al. Evidence of a metabolic reserve in the skeletal muscle of elderly people. Aging
54. Kent-Braun JA. Skeletal muscle fatigue in old age: whose advantage? Exerc Sport Sci Rev
55. Rubinstein S, Kamen G. Decreases in motor unit firing rate during sustained maximal effort contractions in young and older adults. J Electromyography Kinesiol
56. Connelly DM, Rice CL, Roos MR, Vandervoort AA. Motor unit firing rates and contractile properties in tibialis anterior of young and old men. J Appl Physiol (1985)
57. Dalton BH, Jakobi JM, Allman BL, Rice CL. Differential age-related changes in motor unit properties between elbow flexors and extensors. Acta Physiol (Oxf)
58. Kirk EA, Copithorne DB, Dalton BH, Rice CL. Motor unit firing rates of the gastrocnemii during maximal and sub-maximal isometric contractions in young and old men. Neuroscience
59. Roos MR, Rice CL, Connelly DM, Vandervoort AA. Quadriceps muscle strength, contractile properties, and motor unit firing rates in young and old men. Muscle Nerve
60. Jones DA, de Ruiter CJ, de Haan A. Change in contractile properties of human muscle in relationship to the loss of power and slowing of relaxation seen with fatigue. J Physiol
. 2006;576(Pt 3):913–22.
61. Hunter SK, Pereira HM, Keenan KG. The aging neuromuscular system and motor performance. J Appl Physiol (1985)
62. Vandervoort AA. Aging of the human neuromuscular system. Muscle Nerve