Force-time characteristics during sustained maximal handgrip effort according to age and clinical condition.

BACKGROUND: Muscle fatigue, a prominent symptom in older patients, can be assessed by sustained maximal handgrip testing. The force decline during sustained maximal contraction is described for young adults, but data for elderly persons are scarce. The aim of this study was to investigate force-time characteristics during a sustained maximal handgrip effort according to age and clinical condition. METHODS AND MATERIALS: Force-time data were continuously recorded during sustained maximal grip effort in 91 elderly patients (aged 83±5years), 100 elderly controls (aged 74±5years) and 100 young controls (aged 23±3years). The force-time curve was divided in 4 parts per 25% strength drop observed. Time (representing fatigue resistance (FR)) was measured during which grip strength (GS) dropped to 75% (FR75), 50% (FR50), 25% (FR25) of its maximum and to exhaustion (FRexhaustion). Grip work ((GW), the area under the force-time curve) was measured for the 4 parts as well as for the first 20 and 30s of the fatigue protocol test. Strength decay (GWdecay), defined as the difference between the area under the curve (% GW) and a theoretical maximal area under the curve (assuming there's no strength drop), was also studied. In the elderly participants, relationships (controlling for age and sex) of GS, FR and GW with circulating IL-6 and TNF-α were analyzed. RESULTS: FRexhaustion was similar for all groups, whereas the duration of each of the 4 parts was significantly different between the 3 groups. FR75 was shortest in old patients (p=0.004), FR75-50 was almost twice as long in old community-dwelling compared to old patients and young controls (p<0.001). This contrast was inverted for FR50-25 which was significantly shorter in old community-dwelling compared to the other groups (p=0.013). FR25-exhaustionwas significantly longer in young controls compared to the groups of older participants (p=0.017). Old patients showed lower GW for the first 2 parts compared to old community-dwelling and young controls. Also, GWdecay values during the first 20 and 30s were significantly higher in old patients compared to old community-dwelling and young controls (both p<0.001). IL-6 was significantly related to lower GSmax, FR75, FR50, FR25, FRexhaustion, GW75, GW50 and GW75-50. CONCLUSION: This is the first study reporting differences in strength decay during a sustained maximal handgrip effort according to age and clinical condition. Old patients showed a particularly rapid decline in GW during the first part of sustained handgrip. GW was also significantly related to circulating IL-6. Future studies should confirm whether a shorter FR test protocol (i.e. until FR75) but using a continuous registration of the strength decay could be more informative in a clinical setting compared to the classical FR test (measuring only FR50).

High Versus Low Load Resistance Training: The Effect of 24 Weeks Detraining on Serum Brain Derived-Neurotrophic Factor (BDNF) in Older Adults.

BACKGROUND: Previously we showed that 12 weeks of mixed-low resistance training (LOW+) significantly increased circulating BDNF in older male individuals. OBJECTIVES: To examine the impact of 24 weeks detraining on circulating BDNF. DESIGN: Randomized intervention study. SETTING: Community-dwelling older adults. PARTICIPANTS AND METHODS: Forty-seven out of 56 participants stopped training (detraining) after 12 weeks of resistance exercise (3x/week) at either HIGH-resistance (5 Males, 5 Females, 2x10-15 repetitions at 80%1RM), LOW-resistance (6 Males, 7 Females, 1x80-100 repetitions at 20%1RM), or mixed-low LOW+-resistance (6 Males, 8 Females, 1x60 repetitions at 20%1RM followed by 1x10-20 repetitions at 40%1RM), of whom 37 (aged 68±5 years) provided sufficient serum samples for BDNF analysis at baseline, 12 week and at 36 weeks (24 weeks detraining). RESULTS: BDNF had initially increased by 31% (from 33.4±10.9 ng/mL to 44.5±13.2 ng/mL, p=0.005) after 12 weeks in the LOW+ exercise group in males and decreased by 26% (from 44.5±13.2 ng/mL to 32.9±10.7 ng/mL) after detraining, though not statistically significant (p=0.082). In females, no significant change in BDNF was found in any of the intervention groups (p>0.05), neither after training, nor detraining. At 36 weeks all of the subgroups showed BDNF levels comparable (all p>0.10) to baseline (before the exercise intervention). CONCLUSIONS: Our results show that a 12-weeks LOW+ resistance exercise increases circulating BDNF in older male subjects but that this reduces back to baseline levels after 24 weeks of detraining. Continuous exercise adherence seems to be needed to sustain the training-induced effects on BDNF in older persons. Additional studies are needed to unravel the underlying mechanisms, as well as to confirm the observed sex difference.

Effects of Physical Exercise on Markers of Cellular Immunosenescence: A Systematic Review.

Aging affects negatively the immune system, defined as immunosenescence, which increases the susceptibility of elderly persons to infection, autoimmune disease, and cancer. There are strong indications that physical exercise in elderly persons may prevent the age-related decline in immune response without significant side effects. Consequently, exercise is being considered as a safe mode of intervention to reduce immunosenescence. The aim of this review was to appraise the existing evidence regarding the impact of exercise on surface markers of cellular immunosenescence in either young and old humans or animals. PubMed and Web of Science were systematically screened, and 28 relevant articles in humans or animals were retrieved. Most of the intervention studies demonstrated that an acute bout of exercise induced increases in senescent, naïve, memory CD4+ and CD8+ T-lymphocytes and significantly elevated apoptotic lymphocytes in peripheral blood. As regards long-term effects, exercise induced increased levels of T-lymphocytes expressing CD28+ in both young and elderly subjects. Few studies found an increase in natural killer cell activity following a period of training. We can conclude that exercise has considerable effects on markers of cellular aspects of the immune system. However, very few studies have been conducted so far to investigate the effects of exercise on markers of cellular immunosenescence in elderly persons. Implications for immunosenescence need further investigation.

Shortcomings in the application of multicolour flow cytometry in lymphocyte subsets enumeration.

The lymphoid system is composed of numerous phenotypically distinct subsets of cells, each of which has a unique role in the effectiveness of an immune response. To distinguish specifically between these subsets, it is mandatory to detect simultaneously different cell surface antigens. This became feasible by the development of multicolour flow cytometric technologies. With these techniques, researchers now have the opportunity to study individual cells in far greater detail than previously possible. However, proper data analysis, interpretation and presentation of results will require a high level of understanding of the intricacies of the technology and the inherent limitations of the acquired data. The present report is intended to contribute to the better understanding of how the flow cytometer operates. This report may help new and inexperienced users to work appropriately with the flow cytometer.

Inflammation-related muscle weakness and fatigue in geriatric patients.

Inflammation in older persons is associated with muscle wasting, leading to frailty and functional decline. Most studies have focused on IL-6 and TNF-α. In order to further elucidate the underlying mechanisms of muscle wasting and reduced muscle mass and strength we investigated a large panel of cytokines and chemokines, as well as cytoprotective heat shock proteins (Hsp), and measured lean body mass (LBM) and grip strength (GS), fatigue resistance (FR), and grip work (GW) in 33 geriatric patients (median age 84 years) admitted with acute infection-induced inflammation. Higher expression of Hsp27 without heat challenge (WHC) in circulating monocytes and lymphocytes correlated with better FR (r=0.363, p<0.05 and r=0.602, p<0.001 respectively) suggesting a protective effect, as Hsp27 is abundant in muscle. On the other hand, higher serum levels of the inflammatory chemokines CCL11/Eotaxin and CCL2/MCP-1 were related to lower GS and lower LBM (r=-0.393, p<0.05; r=-0.431, p<0.05) respectively. Our results point to a complex pattern of pro-and anti-inflammatory substances that interact with skeletal muscle performance during acute inflammation.

Circulating heat shock protein 70 (Hsp70) in elderly members of a rural population from Cameroon: association with infection and nutrition.

Hsp are highly conserved cytoprotective proteins which have been repeatedly portrayed at elevated levels in various infectious diseases, and there are suggestions that the presence of infectious agents may possibly be the root cause of Hsp induction. As organisms age the vulnerability to illnesses such as infection and inflammation increases and late complications due to infectious agents are mostly observed in the older part of the population. Although it is well known that environmental conditions can modulate the susceptibility to infection, and that poor nutritional status can increase the risk of contracting infection when exposed to an infectious agent, the effects of environmental conditions and nutritional status on the heat shock response have not been investigated. Therefore, we studied the heat shock response in a special elderly population living in a remote area in Cameroon, where infection and parasitosis are endemic. Our results indicate a significant increase in Hsp70 serum levels with increasing degree of inflammation. We found negative correlations between Hsp70 levels and micronutrients including vitamin D, vitamin B12, as well as folate, which could be linked to the immune modulating effects of these vitamins.

Surgery-induced inflammation in relation to age, muscle endurance, and self-perceived fatigue.

BACKGROUND: Elective abdominal surgery can be considered as a model for an important acute inflammatory trigger in human participants. The aim of the study was to explore the effect of surgery-induced inflammation on muscle strength, endurance, and self-perceived fatigue and its relation with age. METHODS: Sixty-six elective abdominal surgery patients aged 24-91 years were assessed before and at the second and fourth day after surgical intervention. Outcome parameters were grip strength, muscle endurance, fatigue subscale of the Profile of Mood State and visual analog scale for pain, and the circulating inflammatory mediators C-reactive protein, interleukin (IL)-6, and tumor necrosis factor-alpha (TNF-alpha). RESULTS: All parameters worsened postoperatively (p < .01) and remained significantly (p < .05) worse until the fourth day postsurgery, except for TNF-alpha (no significant change). Older age was related to higher surgery-induced IL-6 levels at the second (p < .05) and fourth postoperative (p < .01) day and to worse self-perceived fatigue and muscle endurance (both p < .05) at the fourth postoperative day. Higher pain levels at the second day following surgery was related to more self-perceived fatigue (p < .05). Worsening muscle endurance following surgery was significantly related to higher IL-6 release following surgery (p < .01) and self-perceived fatigue (p < .05) at the fourth day following the intervention. Age and surgery-induced increase in circulating IL-6 at Day 4 postsurgery was highest in patients showing both worsened muscle endurance and self-perceived fatigue (p < .05). CONCLUSIONS: Surgery-induced inflammation is related to reduced muscle endurance and the sensation of fatigue. Elderly patients suffer from a higher impact of surgery on muscle endurance.

The effect of aging and inflammation on heat shock protein 27 in human monocytes and lymphocytes.

Heat shock proteins (Hsp) are highly conserved proteins and their synthesis is ubiquitous in virtually every species in which they have been sought. In the present study we have investigated the effect of age and inflammation on the induction of Hsp27 in human peripheral blood mononuclear cells, using flow cytometry. Sixty-six healthy control subjects or patients suffering from inflammation participated in the study. In both heat shocked (HS) and non-HS conditions, the percentage of Hsp27 producing lymphocytes as well as the intensity of Hsp27 in lymphocytes and monocytes were negatively influenced by age. The basal levels and also the levels of Hsp27 production after HS were higher for monocytes compared to lymphocytes. In addition, we found that HS resulted in a small but significant increase in the levels of Hsp27 in lymphocytes whereas a significant decrease in Hsp27 was noticed for monocytes. In conclusion, results presented herein provide evidence in support of an age-related decrease in the level of Hsp27, which disappeared in the presence of inflammation. Several relationships between the circulating levels of CRP, IL-6 and TNF-alpha with the various Hsp27 determinations were observed, indicating that cytokines are able to influence the production of Hsp27.

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 Hsp 70 serum concentrations using an optimised ELISA in elderly patients, recruited from a geriatric University Hospital ward. Our results portray positive correlations between the serum levels of Hsp 70 and various markers of inflammation (monocyte count, serum concentration of TNF-alpha, plasma concentrations of C-reactive protein, and fibrinogen), explaining the difference in Hsp 70 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.

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-alpha; 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.

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 degrees 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 degrees 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 degrees C and the serum levels of tumor necrosis factor-alpha 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.

The prevalence of autoantibodies in an elderly sub-Saharan African population.

In the present prospective, census-based study we have investigated the prevalence of organ-specific and non-organ-specific autoantibodies (AAb) in 152 unselected Cameroonians aged 60 years and older living in the community. AAb were detected in 49% of the participants. Non-organ-specific AAb (47%) predominated over organ-specific AAb (7%). Anti-TPO, anti-Tm, anti-Tg and anti-PC AAb were completely absent. RF was the most frequent AAb, being found in 57 (38%) cases. The prevalences of anti-SMA and RF were significantly higher in women than in men (respectively, P=0.023 and P=0.016). Higher serum concentrations of gammaglobulins were accompanied by a higher prevalence of RF (P < 0.0001) and a lower prevalence of ANA (P=0.036). The overall prevalence of AAb was higher in the filaria-infected (60%) compared to the non-infected (42%) participants (P=0.046). There was no significant influence of the vitamin D status, number of pregnancies, physical activity or medication use on the prevalence of AAb. In this study a heterogeneous pattern for the presence of the various AAb was found. Some AAb, which are commonly encountered in other studies on elderly subjects, were completely absent in this population. This diversified pattern of AAb prevalence therefore argues in favour of exogenous influences in the occurrence of AAb in elderly populations.