Short-term heat acclimation is effective and may be enhanced rather than impaired by dehydration

Most heat acclimation data are from regimes longer than 1 week, and acclimation advice is to prevent dehydration. Objectives: We hypothesized that (i) short-term (5-day) heat acclimation would substantially improve physiological strain and exercise tolerance under heat stress, and (ii) dehydration would provide a thermally independent stimulus for adaptation. Methods: Nine aerobically fit males heat acclimated using controlled-hyperthermia (rectal temperature 38.5°C) for 90 min on 5 days; once euhydrated (EUH) and once dehydrated (DEH) during acclimation bouts. Exercising heat stress tests (HSTs) were completed before and after acclimations (90-min cycling in T a 35°C, 60% RH). Results: During acclimation bouts, [aldosterone] plasma rose more across DEH than EUH (95%CI for difference between regimes: 40-411 pg ml -1 ; P=0.03; n=5) and was positively related to plasma volume expansion (r=0.65; P=0.05), which tended to be larger in DEH (CI: -1 to 10%; P=0.06; n=9). In HSTs, resting forearm perfusion increased more in DEH (by 5.9 ml 100 tissue ml -1 min -1 : -11.5 to -1.0; P=0.04) and end-exercise cardiac frequency fell to a greater extent (by 11 b min -1 : -1 to 22; P=0.05). Hydration-related effects on other endocrine, cardiovascular, and psychophysical responses to HSTs were unclear. Rectal temperature was unchanged at rest but was 0.3°C lower at end exercise (P < 0.01; interaction: P=0.52). Conclusions: Short-term (5-day) heat acclimation induced effective adaptations, some of which were more pronounced after fluid-regulatory strain from permissive dehydration, and not attributable to dehydration effects on body temperature. Am. J. Hum. Biol. 26:311-320, 2014. © 2014 Wiley Periodicals, Inc

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

Circulating Heat Shock Protein 70 in Health, Aging and Disease

<p>Abstract</p> <p>Background</p> <p>Heat 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.</p> <p>Results</p> <p>Serum 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.</p> <p>Conclusions</p> <p>The 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.</p

Reaction time in healthy elderly is associated with chronic low-grade inflammation and advanced glycation end product

Chronic inflammation and Advanced Glycation End products (AGE) are associated with sarcopenia. Decreased voluntary muscle activation and increased antagonist coactivation can contribute to age-related muscle weakness. The influence of chronic inflammation and AGE in these neuromuscular mechanisms is not clear. We studied whether a relation exists between circulating levels of inflammatory cytokines and AGEs as well as the interplay between agonist and antagonist muscle activation. We studied 64 community-dwelling old subjects, during a maximal isometric voluntary contraction (MVC) and a reaction-time (RT) test of the upper limb. Twenty-five circulating inflammatory biomarkers were determined. Linear regression showed significant relationships between chronic inflammation and six muscle activation parameters. MIP-1β showed a significant negative relation with antagonist coactivation (during MVC) and antagonist muscle activity during pre-movement time (PMT) and movement time (MT) (during RT). A higher level of pentosidine (AGE) was predictive for a longer PMT. We conclude that in older relatively healthy persons antagonist muscle activation is influenced by chronic inflammation, contributing to age-related muscle weakness. Our results also suggest a mechanical and inflammatory influence of pentosidine in upper limb slowing of movement. These findings show novel insight in underlying mechanisms of age-related muscle weakness.</p

LPS-induced delayed preconditioning is mediated by hsp90 and involves the heat shock response in mouse kidney.

INTRODUCTION: We and others demonstrated previously that preconditioning with endotoxin (LPS) protected from a subsequent lethal LPS challenge or from renal ischemia-reperfusion injury (IRI). LPS is effective in evoking the heat shock response, an ancient and essential cellular defense mechanism, which plays a role in resistance to, and recovery from diseases. Here, by using the pharmacological Hsp90 inhibitor novobiocin (NB), we investigated the role of Hsp90 and the heat shock response in LPS-induced delayed renal preconditioning. METHODS: Male C57BL/6 mice were treated with preconditioning (P: 2 mg/kg, ip.) and subsequent lethal (L: 10 mg/kg, ip.) doses of LPS alone or in combination with NB (100 mg/kg, ip.). Controls received saline (C) or NB. RESULTS: Preconditioning LPS conferred protection from a subsequent lethal LPS treatment. Importantly, the protective effect of LPS preconditioning was completely abolished by a concomitant treatment with NB. LPS induced a marked heat shock protein increase as demonstrated by Western blots of Hsp70 and Hsp90. NB alone also stimulated Hsp70 and Hsp90 mRNA but not protein expression. However, Hsp70 and Hsp90 protein induction in LPS-treated mice was abolished by a concomitant NB treatment, demonstrating a NB-induced impairment of the heat shock response to LPS preconditioning. CONCLUSION: LPS-induced heat shock protein induction and tolerance to a subsequent lethal LPS treatment was prevented by the Hsp90 inhibitor, novobiocin. Our findings demonstrate a critical role of Hsp90 in LPS signaling, and a potential involvement of the heat shock response in LPS-induced preconditioning

Effects on muscle performance of NSAID treatment with Piroxicam versus placebo in geriatric patients with acute infection-induced inflammation. a double blind randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Inflammation is the main cause of disease-associated muscle wasting. In a previous single blind study we have demonstrated improved recovery of muscle endurance following celecoxib treatment in hospitalized geriatric patients with acute infection. Here we further evaluate NSAID treatment with piroxicam in a double blind RCT and investigate the role of cytokines and heat shock proteins (Hsp) with respect to muscle performance. We hypothesized that NSAID treatment would preserve muscle performance better than antibiotic treatment alone, by reducing infection-associated inflammation and by increasing expression of cytoprotective Hsp.</p> <p>Methods</p> <p>Consecutive admissions to the geriatric ward were screened. 30 Caucasian patients, median age 84.5 years, with acute infection-induced inflammation and serum levels of CRP > 10 mg/L were included and randomized to active treatment with 10 mg piroxicam daily or placebo. Assessment comprised general clinical and biochemical parameters, 25 cytokines in serum, intra-and extracellular Hsp27 and Hsp70, Elderly Mobility Scale (EMS) scores, grip strength (GS), fatigue resistance (FR) and lean body mass (LBM). Patients were evaluated until discharge with a maximum of 3 weeks after treatment allocation.</p> <p>Results</p> <p>EMS scores, FR and grip work (GW), a measure taking into account GS and FR, significantly improved with piroxicam, but not with placebo. Early decreases in IL-6 serum levels with piroxicam correlated with better muscle performance at week 2. Basal expression of Hsp27 in monocytes without heat challenge (WHC) was positively correlated with FR at baseline and significantly increased by treatment with piroxicam compared to placebo. Profound modifications in the relationships between cytokines or Hsp and changes in muscle parameters were observed in the piroxicam group.</p> <p>Conclusions</p> <p>Piroxicam improves clinically relevant measures of muscle performance and mobility in geriatric patients hospitalized with acute infection-induced inflammation. Underlying mechanisms may include modifications in the cytokine network and increases in monocytic expression of cytoprotective Hsp27.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN96340690">ISRCTN96340690</a></p

The age-related failure of adaptive responses to contractile activity in skeletal muscle is mimicked in young mice by deletion of Cu,Zn superoxide dismutase

In muscle, aging is associated with a failure of adaptive responses to contractile activity, and this is hypothesized to play an important role in age-related loss of muscle mass and function. Mice lacking the Cu,Zn superoxide dismutase (Cu,ZnSOD, SOD1) show an accelerated, age-related loss of muscle mass and function. This work determined whether adult mice lacking Cu,ZnSOD ( Sod1 −/− mice) show a premature failure of adaptive responses to contractions in a similar manner to old wild-type (WT) mice. Adult Sod1 −/− mice (6–8 months of age) had a ∼ 30% reduction in gastrocnemius muscle mass compared with age-matched WT mice. This lower muscle mass was associated with an activation of DNA binding by NFκB and AP-1 at rest. Measurements of the activity of reactive oxygen species (ROS) in single fibres from the muscles of Sod1 −/− mice at rest indicated an elevation in activity compared with fibres from WT mice. Following 15 min of isometric contractions, muscle fibres from WT mice showed an increase in the intracellular ROS activities and activation of NFκB and AP-1, but no changes in either ROS activity or NFκB and AP-1 activation were seen in the muscles of Sod1 −/− mice following contractions. This pattern of changes mimics that seen in the muscles of old WT mice, suggesting that the attenuated responses to contractile activity seen in old mice result from chronic exposure to increased oxidant activity. Data support the use of the Sod1 −/− mouse model to evaluate potential mechanisms that contribute to the loss of muscle mass and function in the elderly.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79367/1/j.1474-9726.2010.00635.x.pd

Differential impacts of ocean acidification and warming on winter and summer progeny of a coastal squid (Loligo vulgaris)

Little is known about the capacity of early life stages to undergo hypercapnic and thermal acclimation under the future scenarios of ocean acidification and warming. Here, we investigated a comprehensive set of biological responses to these climate change-related variables (2°C above winter and summer average spawning temperatures and ΔpH=0.5 units) during the early ontogeny of the squid Loligo vulgaris. Embryo survival rates ranged from 92% to 96% under present-day temperature (13-17°C) and pH (8.0) scenarios. Yet, ocean acidification (pH 7.5) and summer warming (19°C) led to a significant drop in the survival rates of summer embryos (47%, P<0.05). The embryonic period was shortened by increasing temperature in both pH treatments (P<0.05). Embryo growth rates increased significantly with temperature under present-day scenarios, but there was a significant trend reversal under future summer warming conditions (P<0.05). Besides pronounced premature hatching, a higher percentage of abnormalities was found in summer embryos exposed to future warming and lower pH (P<0.05). Under the hypercapnic scenario, oxygen consumption rates decreased significantly in late embryos and newly hatched paralarvae, especially in the summer period (P<0.05). Concomitantly, there was a significant enhancement of the heat shock response (HSP70/HSC70) with warming in both pH treatments and developmental stages. Upper thermal tolerance limits were positively influenced by acclimation temperature, and such thresholds were significantly higher in late embryos than in hatchlings under present-day conditions (P<0.05). In contrast, the upper thermal tolerance limits under hypercapnia were higher in hatchlings than in embryos. Thus, we show that the stressful abiotic conditions inside the embryo's capsules will be exacerbated under near-future ocean acidification and summer warming scenarios. The occurrence of prolonged embryogenesis along with lowered thermal tolerance limits under such conditions is expected to negatively affect the survival success of squid early life stages during the summer spawning period, but not winter spawning

Co-chaperones are limiting in a depleted chaperone network

To probe the limiting nodes in the chaperoning network which maintains cellular proteostasis, we expressed a dominant negative mutant of heat shock factor 1 (dnHSF1), the regulator of the cytoplasmic proteotoxic stress response. Microarray analysis of non-stressed dnHSF1 cells showed a two- or more fold decrease in the transcript level of 10 genes, amongst which are the (co-)chaperone genes HSP90AA1, HSPA6, DNAJB1 and HSPB1. Glucocorticoid signaling, which requires the Hsp70 and the Hsp90 folding machines, was severely impaired by dnHSF1, but fully rescued by expression of DNAJA1 or DNAJB1, and partially by ST13. Expression of DNAJB6, DNAJB8, HSPA1A, HSPB1, HSPB8, or STIP1 had no effect while HSP90AA1 even inhibited. PTGES3 (p23) inhibited only in control cells. Our results suggest that the DNAJ co-chaperones in particular become limiting in a depleted chaperoning network. Our results also suggest a difference between the transcriptomes of cells lacking HSF1 and cells expressing dnHSF1