Exercise and skeletal muscle ageing: cellular and molecular mechanisms

As we age, our skeletal muscle becomes smaller and weaker. In addition, the remaining muscle is more susceptible to damage, particularly following exercise, recovery from damage is severely impaired and muscle is unable to adapt rapidly following sequential periods of exercise. The mechanisms by which skeletal muscle damage occurs are poorly understood and the role that an increased production of free radical species plays in this damage is controversial. However, evidence is emerging which suggests that an increased production of free radicals may act as an activator of the adaptive response in skeletal muscle, resulting in the increased production of antioxidant enzymes and heat shock proteins (HSPs). The increased content of these proteins facilitates rapid remodelling of muscle and provides considerable protection against subsequent periods of damaging exercise. There is considerable evidence that the production of free radicals is modified during the ageing process. The aim of this review is to examine the possible effects of this modification on the ability of muscle cells to respond to stress and the functional effect that this may have on our muscles as we age.     

Cortistatin affects glutamate sensitivity in mouse hypothalamic neurons through activation of sst2 somatostatin receptor subtype

Cortistatin is a 14-residue putative neuropeptide with strong structural similarity to somatostatin. Even if it shares several biological properties with somatostatin, the effects of cortistatin on cortical electrical activity and sleep are opposite to those elicited by somatostatin. We recently demonstrated that somatostatin could modulate glutamate sensitivity, either positively through activation of the sstl receptor subtype, or negatively through activation of the sst2 receptor subtype in hypothalamic neurons in culture which express almost exclusively these two sst subtypes. Thus, in the present study we compared the effects of cortistatin and somatostatin in hypothalamic neurons in culture, in order to define the former peptide activity on both subtypes. We first determined that the affinities of cortistatin and somatostatin were similar on cloned rat sstl and sst2 receptor subtypes in transfected cells and hypothalamic neurons membranes. We then found that cortistatin, like somatostatin, depresses the glutamate response but, unlike somatostatin, never potentiates glutamate sensitivity in hypothalamic neurons. The observed effect of cortistatin is strongly suggestive of an activation of the somatostatin sst2 receptor subtype in hypothalamic neurons in culture.     

Candida albicans colonization on an intragastric balloon

Here we present the case of Candida albicans colonization on an intragastric balloon placed for weight loss. A 52‐year‐old obese woman achieved a BMI reduction of 10.9 kg/m² within 7 months as a result of a BioEnterics Intragastric Balloon and a well‐balanced, low‐calorie diet. During endoscopy for balloon removal, the balloon, which was well impacted in the gastric fundus, was found to be lime green in color with clusters of cone‐shaped cultures on its surface. Microbiology assessment revealed the presence of Candida albicans, although the patient was totally asymptomatic.     

Attenuated HSP70 response in skeletal muscle of aged rats following contractile activity

The aim of this study was to investigate the production of HSP70 in gastrocnemius muscles from adult (6-month-old) and aged (28-month-old) rats following contractile activity. At 24 h following a period of repeated isometric contractions, muscles from adult rats contained significantly elevated levels of HSP70 compared with nonexercised muscle. This was not evident in muscles from aged rats. This attenuated response may play a major role in development of the age-related functional deficit that occurs in skeletal muscle.     

Somatostatin receptors in wildtype and somatostatin deficient mice and their involvement in nitric oxide physiology in the retina

The present study investigated the localization and density of somatostatin (SRIF) receptor subtypes (sst(1-5)) and SRIF-nitric oxide (NO()) interactions in the retina of wildtype [WT, (+/+)] and somatostatin deficient mice [SRIF (-/-)]. Immunohistochemistry and radioligand binding studies with subsequent autoradiography were performed. Monoclonal antibodies [SRIF, protein kinase C (rod bipolar cells marker), microtubule associated protein 1A (ganglion cell marker)] and polyclonal antibodies (anti-sst(1), sst(2A), sst(4) receptor) were applied to 10-14 microm sections of retinas fixed in paraformaldehyde. NADPH-diaphorase reactivity was assessed histochemically. [(125)I]LTT SRIF-28 alone or in the presence of MK678 (sst(2) agonist) and [(125)I]Tyr(3)-octreotide were employed to quantify sst(1-5), sst(1/4)and sst(2/5) receptor densities, respectively. sst(1), sst(2A), and sst(4) receptor immunoreactivities were observed in processes of the inner plexiform layer (IPL), rod bipolar, and in ganglion cells and processes, respectively, in WT and SRIF (-/-) mice. Specific [(125)I]LTT SRIF-28 and [(125)I]Tyr(3)-octreotide binding was increased significantly in SRIF (-/-) mice. NADPH-diaphorase staining was localized in photoreceptors and amacrine cells, but not rod bipolar and ganglion cells. Also, NADPH-diaphorase staining was not colocalized with sst(1), sst(2A) or sst(4) receptor immunoreactivity. These results demonstrate an upregulation of SRIF receptors in mice lacking SRIF, but no evident SRIF-NO(*) interaction was observed in the mouse retina.     

Fentanyl treatment reduces GABAergic inhibition in the CA1 area of the hippocampus 24 h after acute exposure to the drug

The effect of in vivo fentanyl treatment on synaptic transmission was studied in the CA1 area of the rat hippocampus. Animals were treated either with saline or fentanyl (4 × 80 μg/kg, s.c./15 min). Intracellular in vitro recordings were obtained, 24 h after treatment, from CA1 pyramidal neurons. No difference in pyramidal neuron basic membrane properties or postsynaptic membrane excitability was observed between neurons from saline- and fentanyl-treated animals. The peak amplitude of fast (f-) and slow (s-) components of IPSPs elicited in standard ACSF and the peak amplitude and rate of rise of isolated f- and s-IPSPs elicited in the presence of antagonists (CNQX, 10 μM; AP-5, 10 μM; CGP 55845, 1 μM; and bicuculline methochloride, 10 μM), in response to various stimulus intensities, was smaller in fentanyl-treated animals. Conversely, the rising slope of excitatory responses was similar in neurons from saline- and fentanyl-treated animals. Furthermore, in fentanyl-treated animals, lower stimulus strengths were required to elicit subthreshold excitatory responses of the same amplitude suggesting that acute exposure to fentanyl increases susceptibility of pyramidal neurons to presynaptic stimulation. GABA immunohistochemistry revealed lower GABA content in processes and neuronal somata suggesting diminished GABA release onto pyramidal neurons. We conclude that acute in vivo exposure to fentanyl is sufficient to induce long-lasting reduction in GABA-mediated transmission, rather, than enhanced excitatory transmission or modulation of the intrinsic excitability of pyramidal neurons. These findings provide evidence regarding the mechanisms involved in the early stages of tolerance development towards the analgesic effects of opioids.     

Age-related changes in skeletal muscle: changes to life-style as a therapy

As we age, there is an age-related loss in skeletal muscle mass and strength, known as sarcopenia. Sarcopenia results in a decrease in mobility and independence, as well as an increase in the risk of other morbidities and mortality. Sarcopenia is therefore a major socio-economical problem. The mechanisms behind sarcopenia are unclear and it is likely that it is a multifactorial condition with changes in numerous important mechanisms all contributing to the structural and functional deterioration. Here, we review the major proposed changes which occur in skeletal muscle during ageing and highlight evidence for changes in physical activity and nutrition as therapeutic approaches to combat age-related skeletal muscle wasting.     

The immune response in hemodialysis patients following physical training

Abstract The effects of mild physical training on the cell-mediated and humoral immune responses were studied in 18 patients with end-stage renal disease (6.5±5.2 years on hemodialysis) participating in a six month exercise renal rehabilitation program. They were matched with 14 untrained patients for sex, age, years on hemodialysis and causes of renal disease. Serum immunoglobulins (IgA, IgM, IgG), IgG subclasses (IgG₁, IgG₂, IgG₃, IgG₄), complement components (C₃, C₄), interleukins IL-2, IL-4, IL-6, subpopulations of T lymphocytes and panel reactive lymphocytotoxic antibodies were determined on all patients. By the end of the study, peak aerobic capacity (VO₂ peak) was significantly improved by 42% in the trained group. This improvement was followed by a non-significant increase in IgE (by 13.8%) and in IgM (by 3%) and a decrease in IgA (by 17.5%, p<0.05), while the IgG levels remained constant. In the control group, there was no change in the levels of immunoglobulins. The values of interleukins, IgG subclasses, complement, lymphocytotoxic antibodies and T lymphocyte subsets remained almost unchanged in both groups. Finally, during the study, common upper respiratory infections were more often in the controls (58%), than in the trained patients (31%). The results suggest that physical training improves clinically the immune defense mechanisms in hemodialysis patients, although it does not significantly change cell-mediated and humoral immune responses.