Handgrip performance in relation to self-perceived fatigue, physical functioning and circulating IL-6 in elderly persons without inflammation

With advancing age skeletal muscle mass and strength decrease dramatically, a phenomenon called sarcopenia [1]. In aging research, grip strength has often been used as an indicator of general muscle strength, since it is a parameter easy to measure. Indeed, age-related changes in grip strength are well described [2] and appear to be similar to the strength losses in other muscle groups [3]. Therefore, grip strength is a useful tool in the clinical evaluation of geriatric patients [3, 4]. Severe inflammation, as seen during acute infections, dramatically worsens sarcopenia-induced reduction in grip strength [5]. Also, in well-functioning elderly persons chronic low-grade inflammation is associated with a worse degree of sarcopenia and reduced grip strength [6]. Low grip strength is recognized as one of the characteristics of frailty, as are inflammation and the sensation of fatigue [4, 7–10]. Due to sarcopenia, older or ill persons will function closer to their limit of maximal strength [11, 12]. Since daily activities in the elderly often require sustained intense muscle contractions (e.g. when bearing shopping bags), these may be more challenging given the reduced muscle strength, and could explain the common sensation of fatigue. This tiredness during daily activities is not a trivial symptom but a predictor of disability and mortality in older individuals [13, 14].

In a general population, the sensation of fatigue is very common (in respectively 20.4% and 14.3% of women and men) [15]; it is predominantly (in 98%) present in residents of long-term care facilities [16]. Contrary to maximal grip strength, the physical resistance of the muscles to fatigue is not often measured in the clinical evaluation of elderly patients. Previously, we have studied grip strength as well as handgrip fatigue resistance in elderly subjects in different clinical conditions [5, 17, 18]. Subjects were instructed to sustain maximal grip effort as long as possible, and fatigue resistance was expressed as the time during which grip strength dropped to 50% of its maximum. From these studies, the handgrip fatigue resistance, more than grip strength, appeared to be closely related to the clinical condition of the subjects. However, it is not clear whether reduced muscle fatigue resistance is also related to sensations of fatigue.

The aim of this study was to investigate if the physical resistance of the handgrip muscles to fatigue is related to self-perceived fatigue and physical functioning in elderly community-dwelling persons. Since inflammation is related to both reduced muscle fatigue resistance [5, 18] and increased fatigue perception [19, 20], here we report a first explorative study in elderly persons without inflammation. In this study, we describe a parameter reflecting the work delivered by the muscles of the forearm during the fatigue resistance test, which we called Grip Work. In fact, muscle strength becomes functional when it can be maintained for a certain time. Also, resistance to fatigue of the muscles is only relevant in daily life when sufficient muscle strength can be developed. The capacity to generate a certain amount of muscle work attains functionally significant dimensions when it can be applied to deliver mechanical work, i.e. to move a given weight over a certain distance. In this context, the body weight of the subject can be of critical importance and heavier subjects might encounter more difficulty and might experience more fatigue when functioning with similar muscle performance than leaner persons. Therefore, we have also corrected the scores of handgrip performance for body weight. Finally, the relation of handgrip performance with circulating Interleukin(IL)-6 was investigated. Previously, we found negative correlations between IL-6 with grip strength and fatigue resistance in inflammatory geriatric patients [5, 18]. Elderly, even when considered heallthy, frequently present low-grade inflammation [21]. Also, IL-6, besides its implication in acute inflammation, has been reported to have a signalling function, linked to muscle performance [22].

When corrected for body weight, higher muscle fatigue resistance was significantly related with less perceived fatigue (p < .05 for both male r = -0.45 and female r = -0.63 on the item WHOQOL F2.4, r = -0.42 p < .05 for the male on the VAS-F and r = 0.59 p < .05 for the female on the Mob-T). As shown in table 4, grip strength in the male participants expressed per kg body weight was significantly related to all self-perceived fatigue items (all p < .05, p < .01 on WHOQOL F2.4) as well as with self-rated physical functioning (p < .01). Also in the female, grip strength corrected for body weight related significantly with self-assessed physical functioning (p < .05). In both male and female participants grip work per kg body weight correlated significantly with self-perceived fatigue (for the male p < .01 on VAS-F and on WHOQOL F2.4, and p < .05 for Mob-T; for the female p < .01 on Mob-T and on WHOQOL F2.4). Corrected grip work related positively with self-rated physical functioning (p < .01 in both male and female).

In this explorative study we have investigated the relationships between handgrip performance and the self-perceived sensation of fatigue in well-functioning elderly persons. In elderly subjects, fatigue might not allways be perceived as such and might be expressed as symptoms related to the occurrence of fatigue. Therefore, we have approached fatigue using different instruments, each representing fatigue in another context. On the one hand, actual fatigue sensation was scored as such on a VAS-scale. On the other hand, we evaluated the extend to which fatigue had an impact on the quality of life (WHOQOL F2.2 & F2.4) or was provoked by daily activities (Mob-Tiredness scale). Finally, self-rated physical functioning was recorded, since limitation in physical functioning might also be an expression of fatigue.

In the male subjects muscle fatigue resistance (time until grip strength drops to 50% of its maximum during sustained contraction) was significantly related with the actual sensation of fatigue, as assessed with the VAS-F (p < .05). Also, better grip strength was significantly related to less actual fatigue sensation (VAS-F, p < .05), less tiredness during daily activities (Mob-T, p < .05) and less perturbation due to fatigue (WHOQOL F2.4, p < .05). These findings support the hypothesis that elderly having more muscle strength probably need to engage less of their maximal strength in order to perform daily activities, and thus get less easily fatigued. For the female participants, the correlation coefficients were in the same direction, but did not reach significancy. The way fatigue is perceived might differ between elderly male and femal subjects. In this context, also Wijeratne et al. [31] found some differences in the relationship between musculoskeletal and fatigue symptoms according to gender in elderly persons. Probably, in healthy subjects fatigue resistance reflects mainly the physiological ability of skeletal muscles to sustain maximal contractions, and is less linked to fatigue perception or motivation. Other reports also indicate that during sustained maximal muscle contraction, force drops to 50% of the initial value within about one minute and that almost all loss in force is due to mechanisms within the contracting muscles [32–34].

When analyzing grip work, a parameter reflecting the total work delivered by the handgrip muscles during the fatigue resistance test, significant relations were found with self-rated fatigue in both the male (VAS-F and WHOQOL F2.4, both p < .01) and the female (Mob-T and WHOQOL F2.4, both p < .05). This is the first description of grip work as a parameter for muscle performance. Grip work integrates the maximal muscle strength with the time during which the muscle contraction can be maintained before the strength drops to 50% of its maximum. In fact, maximal grip strength reflects the capacity of the muscles to generate a large force in a very short time. In addition, grip work estimates the ability to sustain that strength in time. Specifically the latter aspect of muscle performance is important during daily activities that need sustained muscle activity (e.g. when lifting, manipulating or bearing objects). The significant relationship of grip work with self-perceived sensation of fatigue supports the validity of this parameter as a functional outcome measure in the clinical evaluation of elderly subjects.

From a functional viewpoint, the generated force output of muscles is efficient when it allows performing daily activities in a comfortable manner. In this context body mass can be of critical importance. In our study, we have corrected the parameters of handgrip performance for body weight and explored their relationships with self-perceived fatigue. When expressed per kg body weight, the muscle fatigue resistance was significantly related to self-rated fatigue (VAS-F for the male and Mob-T for the female, both p < .05) and the extend to which the subjects were bothered by fatigue (WHOQOL F2.4, p < .05 for both male and female). When expressed per kg body weight, also the relations of grip strength and grip work with self perceived fatigue became more visible by means of higher correlation coefficients in both male and female participants. Indeed, daily activities might be more challenging for obese persons compared to leaner subjects having the same muscle performance, and might thus be more easily accompanied with fatigue.

We have also studied the relation of handgrip muscle performance with self-rated physical functioning. Grip strength and grip work were significantly related with physical functioning in both male and female participants. When corrected for body weight, these correlations remained of the same magnitude and statistically significant. However, no significant relationship was found between muscle fatigue resistance and self-rated physical functioning. This might be explained by the fact that fatigue resistance, defined as the ability to maintain one's maximal effort, is independent of the initially produced force. Persons presenting a higher grip strength thus can have the same fatigue resistance as weaker ones. For physical functioning, both the maximal strength as well as the time it can be maintained are of critical importance, and thus the grip work (eventually corrected for body weight) might be the best parameter to measure in the physical evaluation of elderly subjects.

We looked for relationships between handgrip performance and circulating levels of IL-6. In our male participants fatigue resistance and grip work correlated positively (p < .05) with IL-6. This is in contrast with our previous studies in hospitalised geriatric patients, where worse muscle fatigue resistance was significantly related to higher levels of circulating IL-6 [5, 18]. Probably the relation of the cytokine IL-6 with muscle performance depends on the situation in which it is released in the blood circulation. In the present study, participants showed no evident inflammatory activity (CRP < 3 mg/L), and thus the signalling role of IL-6 might be different compared to situations accompanied with severe inflammation (CRP > 10 mg/L) as in our previous work [5, 18]. Indeed, some authors have pointed out possible mechanisms responsible for positive relations between IL-6 signalling and muscle performance [35, 36]. Noteworthy, these relationships were attenuated when handgrip fatigue resistance and grip work were corrected for body weight. It can not be excluded that the correlations with IL-6 were influenced by the body weight of the participants, since it has been shown that adiposity and type-2 diabetes is positively linked to higher levels of circulating IL-6 [37]. However, in that case, lower muscle performance would be expected. Clearly, this 'IL-6 paradox' on muscle performance needs further study.

As a final point, it can not be excluded that some of the non-significant correlations in our study are due to a type-2 error. However, for this study we have contacted 274 elderly subjects with normal cognitive function, from whom a large number had to be excluded. Indeed, given the burden of chronic late-life disease and polypharmacy, many elderly subjects show inflammation or use anti-inflammatory drugs. Although participants included in this study and non-participating elderly were similar regarding age and cognitive function, selection bias cannot be completely excluded. On the other hand, the fact that the study population consisted in completely independent and well functioning elderly persons probably resulted in a low variability of fatigue sensations that might have masked some relationships. It is our opinion that the results of this study support the validity of handgrip fatigue resistance, grip work and maximal grip strength as relevant outcome measures in the physical evaluation of elderly patients. Further research with these evaluation instruments, documenting elderly persons in different clinical settings might contribute to its validity and clinical usefulness.

From the results of our study we can conclude that handgrip performance is related to self-perceived fatigue and physical function in elderly, independently living persons without inflammation. Weaker and less fatigue resistant elderly subjects are more fatigued, experience more tiredness during daily activities and are more bothered by fatigue sensations. Body weight seems to play an important role in the relation of muscle performance to fatigue perception. Elderly patients complaining from fatigue should be physically assessed, both evaluating maximal grip strength and fatigue resistance, allowing the calculation of grip work, which integrates both parameters. Grip work might best reflect the functional capacity resulting from the development of a certain strength level in relation to the time it can be maintained.