The relationship between self-perceived fatigue, muscle endurance, and circulating markers of inflammation in participants of the Copenhagen aging and Midlife Biobank (CAMB)

Abstract

Background: Fatigue, low muscle endurance, muscle weakness and low-grade inflammation are strongly related to frailty at higher age. When signs of self-perceived fatigue and low muscle endurance are interrelated with low-grade inflammation at midlife, they might be used as early markers for frailty. This study investigated whether the interrelationships among self-perceived fatigue, muscle endurance and inflammation can be observed at midlife.

Methods: A total of 965 participants of the Copenhagen Aging and Midlife Biobank (aged 52 ± 4 years, 536 males, 426 females) were assessed for self-perceived fatigue (20-item multidimensional fatigue inventory), muscle endurance (grip work), circulating markers of inflammation (hsCRP, IL-6, IL-10, TNF-alpha and IFN-γ), daily physical activity (PAS-2), body composition (%body fat assessed by bio-impedance) and self-reported health status. Participants were categorised (correcting for age and gender) according to high fatigue and/or low muscle endurance, differences in inflammatory profile between fatigue categories were assessed by ANCOVA (corrected for PAS-2, %body fat and presence of inflammatory conditions).

Results: Overall, muscle endurance, fatigue and inflammatory markers were significantly interrelated. Higher levels of hsCRP (p < 0.001), IL-6 (p < 0.001), IL-10 (p = 0.035) and TNF-alpha (p = 0.028) were observed in participants presenting both low muscle endurance and high fatigue. IFN-γ was highest in those with high fatigue but normal muscle endurance (p = 0.015).

Conclusions: Middle-aged participants with higher fatigue in combination with low muscle endurance show higher levels of inflammation, independently from physical activity, body fat and inflammatory pathology. The underlying mechanisms should be identified and future studies should also investigate whether these individuals show early signs of reduced physiological reserve capacity, which in later life come to full expression by means of frailty.

Keywords: Ageing; Frailty; Grip work; Handgrip strength; Muscle fatigue.

Fig. 1

Circulating levels of inflammatory mediators according to self-perceived fatigue and muscle endurance. Bars represent mean ± standard error. Inflammatory markers are expressed as log(10) transformed values. Since all log(10) transformed values For IFN-γ were negative (IFN-γ concentrations were >1) all data were summed by 1 in order to optimise the visual interpretation of figure 1E. ANCOVA analysis (with weekly physical activity, percentage body fat and presence of inflammatory conditions as covariates) revealed significant differences between the subgroups for A hs-CRP (p<0.001), B IL-6 (p<0.001), C TNF-alpha (p=0.028), D IL-10 (p=0.035) and E IFN-γ (p=0.015). Overall, participants with high self-perceived fatigue and low muscle endurance presented the highest (except for IFN-γ, figure 1E) and those with normal self-perceived fatigue and normal muscle endurance the lowest levels of inflammatory mediators. F Post-hoc pairwise comparisons showed that participants with high self-perceived fatigue and low muscle endurance presented significantly higher hs-CRP and IL-6 levels compared to those with normal self-perceived fatigue and normal muscle endurance (p<0.01), as well as lower hs-CRP compared to those with normal self-perceived fatigue but low muscle endurance (p<0.01). Participants with normal self-perceived fatigue and normal muscle endurance showed also significantly lower levels of IL-6 compared to those with normal self-perceived fatigue and low muscle endurance (p<0.05), and lower hs-CRP, IL-6 and IFN-γ compared to participants with high self-perceived fatigue and normal muscle endurance (respectivelyp<0.05, p<0.01 and p<0.01)