Rose Njemini

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

BackgroundLow grip strength is recognized as one of the characteristics of frailty, as are systemic inflammation and the sensation of fatigue. Contrary to maximal grip strength, the physical resistance of the muscles to fatigue is not often included in the clinical evaluation of elderly patients. The aim of this study was to investigate if the grip strength and the resistance of the handgrip muscles to fatigue are related to self-perceived fatigue, physical functioning and circulating IL-6 in independently living elderly persons.MethodsForty elderly subjects (15 female and 25 male, mean age 75 ± 5 years) were assessed for maximal grip strength, as well as for fatigue resistance and grip work (respectively time and work delivered until grip strength drops to 50% of its maximum during sustained contraction), self perceived fatigue (VAS-Fatigue, Mob-Tiredness scale and the energy & fatigue items of the WHOQOL-100), self rated physical functioning (domain of physical functioning on the MOS short-form) and circulating IL-6. Relationships between handgrip performance and the other outcome measures were assessed.ResultsIn the male participants, fatigue resistance was negatively related to actual sensation of fatigue (VAS-F, p < .05) and positively to circulating IL-6 (p < .05). When corrected for body weight, the relations of fatigue resistance with self-perceived fatigue became stronger and also apparent in the female. Grip strength and grip work were significantly related with several items of self-perceived fatigue and with physical functioning. These relations became more visible by means of higher correlation coefficients when grip strength and grip work were corrected for body weight.ConclusionWell functioning elderly subjects presenting less handmuscle fatigue resistance and weaker grip strength 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.

Elevated serum heat-shock protein 70 levels in patients with acute infection: use of an optimized enzyme-linked immunosorbent assay.

Heat‐shock proteins (Hsps) are highly conserved throughout evolution and evoke great interest both in basic biology and in medicine. They are expressed in small quantities under normal conditions, and their expression can be strongly induced by several stressors. Although their action is basically intracellular, it is now obvious that these proteins can be released into the extracellular environment from viable cells. In this study, the human Hsp 70 serum concentrations were determined using an optimized, cost‐effective enzyme‐linked immunosorbent assay (ELISA). The average intra‐assay variation was 6%, whereas the average interassay variation was 9%. The sensitivity of the assay was 10 ng/ml, and spiking experiments showed recoveries between 101 and 109%. As an application of the technique, we have investigated the serum levels of human Hsp 70 in patients with infection and in healthy subjects. Our data show significantly higher levels of Hsp 70 (P  = 0.003) in patients compared to control subjects. Positive correlations were noticed between the serum levels of Hsp 70 and various markers of inflammation (IL‐6; r = 0.579, P = 0.009, TNF‐α; r  = 0.552, P  = 0.012, IL‐10; r  = 0.361, P = 0.002). We conclude that Hsp 70 is involved in inflammation of infectious origin. The interindividual variation in the serum concentration of Hsp 70 precludes the use of serum Hsp 70 levels to distinguish patients from healthy subjects.

Biochemical Changes in Response to Intensive Resistance Exercise Training in the Elderly

Background: It is assumed that low-grade inflammation, characterized by increased circulating IL-6 and TNF-α, is related to the development of sarcopenia. Physical exercise, especially high intensity resistance training, has been shown to be effective in restoring the strength deficit in the elderly. Intensive exercise is accompanied by significant release of IL-6 and TNF-α into the blood circulation, but does not result in muscle wasting. Exercise-induced changes in heat-shock protein (Hsp), responsible for cellular protection during stressful situations, might interfere with the acute phase reaction and muscle adaptation. Objective: To investigate if intensive strength training in elderly persons induces changes in Hsp70 expression, and if these changes are related to changes in the acute phase reaction or muscle adaptation. Methods: 31 elderly persons (aged 68.4 ± 5.4 years) performed 6 weeks’ intensive strength training. At baseline and after 6 weeks, muscle strength, functional performance (physical activity profile, 6-min walk, 30- second chair stand, grip strength, chair sit & reach and back scratch), linear isokinetic leg extension, circulating IL-6, TNF-α, IL-10 and TGF-β, and Hsp70 in monocytes (M) and lymphocytes (L) immediately after sampling (IAS), after incubation at 37 and 42°C were determined. In 12 participants, cytokines were determined in untrained and trained conditions before and after a single training session. Results: After 6 weeks’ training, muscle strength and functional performance improved significantly, together with decreased Hsp70 IAS and Hsp70 37°C and increased Hsp70 42°C (all p < 0.05). Strength gains correlated positively with baseline Hsp70 37°C and training-induced changes of Hsp70 42°C in M and L. In an untrained condition, training induced an increase of IL-6 (p < 0.05) and a tendency of IL-10 to decrease (p = 0.06). In a trained condition the decrease of IL-10 disappeared. Baseline physical activity and 6-min walk distance correlated negatively with circulating IL-6 (p < 0.05); except for a negative correlation between TGF-β and Hsp70 37°C L (p < 0.05), no significant relationships were found between cytokines and Hsp70. After the training program, Hsp70 37°C was negatively related to circulating TNF-α, IL-10 and TGF-β. Conclusion: Strength training in the elderly induces changes in Hsp70 expression, associated to strength gains and circulating cytokines.

Age-Related Decrease in the Inducibility of Heat-Shock Protein 70 in Human Peripheral Blood Mononuclear Cells

We have investigated the effect of age and of the presence of proinflammatory cytokines on Hsp 70 production in human peripheral blood mononuclear cells, using flow cytometry. Twenty-seven women and 23 men, all apparently healthy, participated in the study. At 37°C, the percentage of Hsp 70-producing monocytes and lymphocytes, as well as the level of Hsp 70 in monocytes, were negatively influenced by age. After exposure of the cells to 42°C, the increase of Hsp 70 production was more pronounced in monocytes than in lymphocytes; both the intensity of Hsp 70 production and the percentage of Hsp 70-producing cells were negatively influenced by the age of the subjects, as well for monocytes as for lymphocytes. There was a negative correlation between the intensity of Hsp 70 production by monocytes exposed to 42°C and the serum levels of tumor necrosis factor-α and interleukin-6. In conclusion, in human monocytes and lymphocytes, heat-induced Hsp 70 production is reduced with increasing age and is negatively influenced in monocytes by proinflammatory cytokines.

Inflammatory status as an important determinant of heat shock protein 70 serum concentrations during aging.

Heat shock proteins (Hsp) form a large family of proteins that are ubiquitously present in all organisms. In the absence of destabilising stimuli, Hsp are expressed at low levels, but their expression can be highly induced by various noxious conditions such as heat, oxygen stress and infection. Hsp have been reported to interfere with inflammatory processes and their induction is well known to decrease with aging. In the present study we have investigated Hsp70 serum concentrations using an optimised ELISA in elderly patients, recruited from a geriatric University Hospital ward. Our resultsportray positive correlations between the serum levels of Hsp 70 and various markers of inflammation (monocyte count, serum concentration of TNF-α, plasma concentrations of C-reactive protein, and fibrinogen), explaining the difference in Hsp70 serum concentrations in these subjects with various degrees of inflammation. We conclude that Hsp 70 is involved in inflammatory diseases and that the serum level of Hsp 70 is directly linked to the inflammatory status of the subject. However, the nature of this relationship remains to be elucidated.

Circulating Heat Shock Protein 70 in Health, Aging and Disease

BackgroundHeat shock proteins (Hsp) are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. Recent studies have identified circulating Hsp as an important mediator in inflammation - the effects of low-grade inflammation in the aging process are overwhelming. While much is known about intracellular Hsp70, scant data exist on circulating Hsp70 in the aging context. Therefore, the objectives of this study were to investigate the effect of age and disease on circulating Hsp70 and, in particular, to evaluate the association between circulating Hsp70 and inflammatory parameters.ResultsSerum Hsp70, Interleukin (IL) -10, IL-6 and Tumor Necrosis Factor (TNF) alpha concentrations were determined in 90 hospitalised geriatric patients (aged 83 ± 6 years) and in 200 community-dwelling control subjects (100 elderly, aged 74 ± 5 years, and 100 young, aged 23 ± 3 years). In the community-dwelling elderly, serum Hsp70 and IL-10 concentrations were significantly lower and IL-6 was significantly higher when compared to healthy young control subjects. Elderly patients presenting inflammation (CRP serum levels ≥5 mg/L) showed significantly (p = 0.007) higher Hsp70 values; and Hsp70 correlated positively (p < 0.001) with IL-6 and CRP, but not with TNF-alpha or IL-10. A significant association was also noted between Hsp70 levels and the degree of dependency and cognitive decline in geriatric patients.ConclusionsThe present data provide new evidence that serum concentration of Hsp70 decreases with age in a normal population. Our study also shows that higher levels of Hsp70 are associated with inflammation and frailty in elderly patients.

Effect of advanced glycation end product intake on inflammation and aging: a systematic review

Aging is associated with a chronic low-grade inflammatory status that contributes to chronic diseases such as age-related muscle wasting, kidney disease, and diabetes mellitus. Since advanced glycation end products (AGEs) are known to be proinflammatory, this systematic review examined the relation between the dietary intake of AGEs and inflammatory processes. The PubMed and Web of Science databases were screened systematically. Seventeen relevant studies in humans or animals were included. The intervention studies in humans showed mainly a decrease in inflammation in subjects on a low-AGE diet, while an increase in inflammation in subjects on a high-AGE diet was less apparent. About half of the observational studies found a relationship between inflammatory processes and AGEs in food. When the results are considered together, the dietary intake of AGEs appears to be related to inflammatory status and the level of circulating AGEs. Moreover, limiting AGE intake may lead to a decrease in inflammation and chronic diseases related to inflammatory status. Most of the trials were conducted in patients with chronic kidney disease or diabetes, and thus additional studies in healthy individuals are needed. Further investigation is needed to elucidate the effects of lifetime exposure of dietary AGEs on aging and health.

Muscle Endurance in Elderly Nursing Home Residents Is Related to Fatigue Perception, Mobility, and Circulating Tumor Necrosis Factor‐Alpha, Interleukin‐6, and Heat Shock Protein 70

OBJECTIVES: To explore the relationships between muscle endurance and circulating interleukin (IL)‐6, tumor necrosis factor alpha (TNF‐α), and heat shock protein (Hsp)70 in nursing home residents and to assess how muscle endurance relates to self‐perceived fatigue and mobility.

No influence of noradrenaline manipulation on acute exercise-induced increase of brain-derived neurotrophic factor.

PURPOSE To examine the influence of a selective noradrenaline reuptake inhibitor (SNRI) on the exercise-induced increase in circulating brain-derived neurotrophic factor (BDNF). METHODS In a double-blind, placebo-controlled, crossover design, 11 young, healthy male subjects were treated with either placebo or reboxetine. On each occasion, they performed a 60-min cycling exercise at 55% of their maximal power output (Wmax) followed by a time trial (TT) at 75% of Wmax. HR and ratings of perceived exertion were measured. Blood samples were taken at four time points. RESULTS An increase in serum BDNF was found after exercise without any influence of drug administration on BDNF levels. Serum BDNF returned to resting levels after 15 min of recovery. Time trial (TT) performance was significantly worse after reboxetine intake. Serum cortisol increased in both trials during and after exercise and was significantly higher in the reboxetine trial. Also, HR was increased with reboxetine intake, probably because of the sympathomimetic effect of SNRI. Midterm memory was significantly impaired after the exercise protocol without difference between reboxetine and placebo trial. CONCLUSIONS The administration of an SNRI has no effect on the exercise-induced increase in BDNF. However, effects were seen on serum cortisol, HR, and memory. Future research should focus on the effect of regular exercise training in combination with several reuptake inhibitors in both healthy and depressed subjects on BDNF and memory.

Heat shock proteins and chemokine/cytokine secretion profile in ageing and inflammation

We have used a multiplex bead array assay to detect simultaneously 25 different circulating cytokines in 35 control subjects (young versus old) and 29 patients (young versus old) with acute infection. Intracellular PBMC levels of heat shock proteins (Hsp) were determined using flow cytometry. Levels of MIG and IL-6 were higher in the elderly normal subjects and patients, respectively, compared to their young counterparts. Hsp32, Hsp70 and Hsp90 were higher in elderly compared to young normal subjects. This difference disappeared for patients with inflammation who had increased levels of Hsp32, Hsp70 and Hsp90 compared to normal subjects. Most striking, a different pattern of association between cytokines and Hsp was noticed in healthy elderly subjects compared to the other groups of participants. It is concluded that age-related stress, possibly oxidative, which can down-regulate cytokine production with a concomitant up-regulation of Hsp production, could be involved in this differential pattern of association.