Muscle Atrophy In Chronic Obstructive Pulmonary Disease: Molecular Basis And Potential Therapeutic Targets
Esther Barreiro1,2, Ariel Jaitovich3,4
1Respiratory Medicine Department-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, Institute of Medical Research of Hospital del Mar -Hospital del Mar, Parc de Salut Mar, Barcelona Biomedical Research Park , Barcelona 2Centro de Investigación en Red de Enfermedades Respiratorias , Instituto de Salud Carlos III , Division of Pulmonary and Critical Care Medicine, 4 Department of Molecular and Cellular Physiology, Albany Medical College , USA
Contributions: Conception and design: E Barreiro Administrative support: None Provision of study materials or patients: None Collection and assembly of data: None Data analysis and interpretation: None Manuscript writing: All authors Final approval of manuscript: All authors.
Keywords: Chronic obstructive pulmonary disease muscle dysfunction muscle atrophy multifactorial etiology biological mechanisms and potential therapeutic targets
Submitted Apr 18, 2018. Accepted for publication Apr 24, 2018.
Stress Makes You Crave Junk Food
Cortisol is a steroid hormone, and all steroids directly stimulate appetite, explains Dr Leon Creaney, a consultant in Sport & Exercise Medicine at The Manchester Institute of Health & Performance, operated by HCA Healthcare UK.
Fat and sugar trigger the release of dopamine in the brain, which causes pleasure, so people eat to counteract the negative feelings that come with stress. Stress also takes the driving seat when it comes to food choices and portion control. In fact, it affects our brains in a similar way to alcohol, says Uxshely Chotai at The Food Psychology Clinic.
When were stressed or tired, our prefrontal cortex the part of our brain that makes conscious choices for us stops working as effectively, she explains. Were no longer able to consciously control our food choices, and we have less willpower to resist the urge to overeat foods we wouldnt otherwise choose to eat.
Over time, chronic stress damages your cells, making them resistant to insulin. This sends your hunger hormones out of whack, warping your brain’s stop eating signals. Before you know it, youre halfway through a multipack of Mars bars and still feel hungry. Unsurprisingly, this insulin resistance is linked to an increased risk of type 2 diabetes and obesity.
Salidroside Inhibits Oxidative Stress And Inflammaton In Nutrition Deprivation
Oxidative stress and inflammation are two main molecular mechanisms involved in muscle atrophy . To evaluate whether salidroside attenuates myotube atrophy induced by nutrition deprivation through inhibiting oxidative stress and inflammation, we examined ROS levels and inflammatory cytokines. The current study indicated that ROS were markedly induced in the C2C12 myotubes treated with HBSS, as evidenced by the increased DHE fluorescence. Salidroside inhibited the production of ROS in C2C12 myotubes treated with HBSS, which was confirmed by the decreased DHE fluorescence. Moreover, the high doses of salidroside showed better performance in cleaning up ROS, which was similar to the response from NAC in nutrition deprivation-induced myotube atrophy . At the same time, Nox2, Nox4, Nrf2, NQO1, and HO-1 mRNA were determined. Our results suggested that Nox2 and Nox4 mRNA were markedly induced, and Nrf2, NQO1, and HO-1 mRNA were markedly suppressed in the C2C12 myotubes treated with HBSS. Salidroside could reverse the response from nutrition deprivation .
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What Are The Symptoms Of Atrophied Muscles
Atrophied muscle symptoms often depend on the underlying condition leading to muscle wasting. Additionally, the particular muscle groups affected will determine what type of symptoms will ultimately appear. However, the following are some of the most common signs and symptoms of muscle atrophy.
Weak muscles: Due to a loss of strength resulting from muscle losing its tone and becoming flabby. Muscle atrophy sufferers may find even basic exercises like lifting objects difficult to accomplish.
Muscle damage: Can lead to the development of a stooped posture that becomes more and more prominent over time. This may lead to difficulties standing or sitting straight.
Stroke and heart attack: Due to your heart having difficulty pumping blood and occurring in extreme cases. Patients often feel a sudden increase in heart rate, chest pain, and weakness with physical activity. This may be due to the heart not being able to pump as well as it needs to due to years of physical inactivity.
Pain: Simply moving the affected limb may be painful for those affected by muscular atrophy.
Other possible symptoms include
- Difficulty with speaking and swallowing
- Facial weakness
Conventional Medicines Answer To Muscle Wasting
If you voice concerns about muscle fatigue or have trouble with gaining muscles, youre likely to be told by most conventionally-trained doctors that youre just getting older, or that you need more exercise.
We know that muscle mass does decrease with age, but generally, people with chronic inflammatory conditions are more likely to experience it and they see it earlier in life and/or with a quicker progression.
The primary treatment for muscle wasting is physical exercise, with a focus on strength training. While this can be a helpful part of a treatment regimen, it wont address the root cause for people with Hashimotos, and, on its own, is unlikely to reverse the condition.
Muscle wasting can also be challenging for conventional practitioners to tackle without pulling out the prescription pad, as its symptoms can be subtle and non-specific. Often, pain meds or even antidepressants are prescribed, while other doctors may prescribe physical therapy.
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Atrophic Signalling In Skeletal Muscle
Muscle atrophy occurs in response to many insults, including prolonged disuse, ageing and chronic disease such as Type 2 Diabetes Mellitus . Muscle atrophy is the result of a negative balance between the rate of contractile protein synthesis and degradation. In catabolic conditions, muscle atrophy in combination with inactivity can decrease the capacity to perform activities of daily living, quality of life and subsequently increase mortality . The ubiquitin-proteasome, autophagy-lysosome and caspase-3-mediated proteolytic pathways are responsible for protein degradation in muscle and thus contribute to muscle atrophy . In healthy muscle, the degradation of damaged or unfolded proteins is vital for the maintenance of cellular homeostasis . In atrophic conditions such as disuse or diabetes, however, prolonged increased activity of these pathways increases the rate of contractile protein degradation, ultimately leading to muscle atrophy . In addition, decreased protein synthesis is apparent in T2DM and disuse, primarily through decreased activation of the mammalian target of rapamyacin pathway .
Protein synthesis and degradation pathways in skeletal muscle. Arrows represent activation, capped lines represent inhibition. Abbreviations: mTOR, mechanistic target of rapamycin p70S6k, p70S6 kinase IGF-1, insulin-like growth factor 1 FoxO, forkhead box O transcription factor 4EBP1, eukaryotic translation initiation factor 4E-binding protein 1.
Can Stress And Anxiety Cause Muscle Loss
A recent study showed that daily stress and anxiety are associated with muscle loss. There are two major adverse muscle-related outcomes of chronic stress. During chronic stress, your muscles might feel tense and you might feel a decrease in lean muscle mass.
This may eventually lead to muscle atrophy due to the disuse of the body muscle.
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Stress Messes With Your Metabolism
Cortisol sits within a class of hormones called glucocorticoids, which increase blood glucose levels, explains Kim Ingleby, founder of Energised Performance and an Optimum Nutrition Gold Standard Trainer. It promotes the metabolism of carbohydrates, protein and fats and taps into your existing stores to free up energy during severe periods of stress.
With energy levels raging, and no way of burning it off because youre at your desk rather than in a jungle your body releases insulin in an attempt to calm things down. Cortisol reacts by dumping most of the energy as dangerous visceral fat. For this reason, being chronically stressed can fast track you to a swollen belly, even if you eat like an athlete.
Short periods of stress can be beneficial for performance, focus and motivation, but prolonged or overly high levels can have a detrimental effect on our health, says Ingleby. Stress can happen so often we dont even notice it after a while, it becomes our normal state.
The solution: Get moving gently. Take a break from your strenuous sweat sesh and focus on low-intensity aerobic exercise: things like walking, jogging, swimming, and cycling. Yoga is also a great shout.
Penile Atrophy And Arterial Plaque
Officially called atherosclerosis, this is essentially the same process that happens in the arteries leading to your heart that cause a heart attack.
As you get older, plaque builds up on the insides of your arteries. This problem is worse the less healthy your lifestyle.
That process doesnt just happen in your coronary arteries though. It also happens over time on the tiny arteries in your penis.
With a smaller hole for the blood to go through, it takes longer to fill the spongy tissue with blood, which makes if more difficult to get an erection.
Whats more, as the buildup solidifies on the arterial walls in your penis, the spongy tissue in your penis isnt so spongy any more, which means less blood gets trapped in this tissue, leading to a softer erection.
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Exercise Capacity And Peripheral Muscle Function And Structure
As previously demonstrated , in the current investigation, COPD patients with muscle wasting exhibited severe impairment of aerobic capacity together with moderate reduction in quadriceps muscle force. The latter parameter was similar within the two groups of patients regardless of their muscle mass. The greater proportions of type II fibres observed within the limb muscles of the muscle-wasted patients, albeit of smaller size, could be a contributing factor. Furthermore, muscle mass was shown to be directly associated with disease severity as measured by FEV1.
Can Low Vitamin D Cause Joint And Muscle Pain
It is often overlooked that low vitamin D levels can have severe side effects. Many individuals dont realize how low they should be biotin.There could be muscles in your joints that become fatigued or upset due to this lack, including some people who suffer from rheumatoid arthritis pain on knees, hips, and other joints.
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Focus On Getting More Building Blocks For Your Muscles
To get the body back on track, we will need to start by supporting it with the building blocks it needs protein, amino acids, and digestive support to properly break down and utilize the protein. Well also need to support the production of natural anabolic steroids by balancing cortisol levels, and eliminating any underlying infections.
Optimize Protein Intake
Remember, the body is breaking down its own muscle protein to fuel its inflammatory stress response. This means your overall requirement for protein will be increased. While we know that inflammation is at the root cause of this and we definitely want to address the inflammation so that we no longer need as much protein, realistically, reducing inflammation to a healthy level may take some time.
In the meantime, we need to get adequate amounts of protein to build the body back up so that the inflammatory response isnt leading to a breakdown of the muscle tissue. A key component of making sure that our muscles get the amino acids that they need to repair and build, is to ensure that we are getting enough of these amino acids into our system.
One obvious way to get more protein is to consume more protein. Consider adjusting your diet to be more based on protein, and minimizing carbs and processed foods .
If you need some recipe ideas, you may want to look into the Paleo-style diet, which focuses largely on quality meats, vegetables, and fruits.
How much protein is needed?
Support Protein Digestion
Why Do My Legs Feel Weak And Heavy
Stress, including anxiety-caused stress, can make your legs feel weak and heavy. Weak and heavy legs is a common symptom of overly apprehensive behavior. For more information, read why anxiety can cause weak and heavy legs. You can also read how to get rid of weak and heavy legs.
There are many medical conditions and medications that can cause legs to feel weak and heavy. You should discuss this symptom with your doctor to rule out a medical cause.
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Why Do My Legs Feel Weak And Tired
Stress, including anxiety-caused stress, can make your legs feel weak and tired. Many people experience legs that feel weak and tired when they are anxious, stressed, or afraid. For more information, read why anxiety can cause a weak and tired feeling in the legs. You can also read how to get rid of legs that feel weak and tired.
There are many medical conditions and medications that can cause legs to feel weak and tired. You should discuss this symptom with your doctor to rule out a medical cause.
Can Low Vitamin D Affect Muscles
There is severe vitamin D deficiency resulting in rickets, which can be due to an improper growth pattern, weakness in muscle tissue, pain in bones and arthritis on joints as a result.It is rare for anything like this to happen.In addition to being lacking in vitamin D, children may suffer acute muscle weakness, a sore or painful muscular condition and poor functionality in their arms or legs.
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Salidroside Inhibits Ubiquitinproteasome System In Denervation
To assess how salidroside attenuates denervation-induced muscle atrophy, we examined evidences for the ubiquitinâproteasome system proteolytic and protein synthesis activities. Interestingly, the elevated expression of muscle-specific E3 ubiquitin ligases Atrogin-1/MAFbx and MuRF1 was suppressed by salidroside in denervated muscles . Intriguingly, these responses from salidroside were also observed in the muscles of NAC administration . These data suggested that salidroside attenuated denervation-induced skeletal muscle atrophy through inhibition of the ubiquitinâproteasome proteolytic pathway.
Figure 8 Salidroside inhibited the expression of ubiquitinâproteasome pathwayâespecially E3 ubiquitin ligases muscle-specific F-box and muscle ring-finger protein-1 , and improved the expression of MHC in TA muscles of mice suffered from sciatic nerve transection. Representative blots of MHC, MAFbx, and MuRF1 in TA muscles. Relative expression of MHC in TA muscles. Relative expression of MuRF1 in TA muscles. Relative expression of MAFbx in TA muscles. Data are expressed as mean Â± SD. **p < 0.01 and ***p < 0.001 versus Ctrl. #p < 0.05 and ##p < 0.01 versus NS.
Transmission Electron Microscopy Analysis
To observe the changes in the mitochondria, the TA muscle was analyzed through TEM analysis. The detailed procedures of TEM for muscle were previously reported . Briefly, 1-mm3-sized muscle was fixed in 2.5% glutaraldehyde followed by post fixation in 1% osmium tetroxide. Muscle sections were analyzed by TEM . A total of 20 fields per mouse performed in three mice per condition were analyzed.
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Inflammatory Cytokines And Nfb Signaling
NFB transcription factors, which play major roles as mediators of immunity and inflammation, are also expressed in skeletal muscle, where they mediate the effect of inflammatory cytokines, particularly tumor necrosis factor- , on muscle wasting and cachexia . In the inactive state, NFB is sequestered in the cytoplasm by a family of inhibitory proteins called IB. In response to TNF, the IB kinase complex phosphorylates IB, resulting in its ubiquitylation and proteasomal degradation. This leads to nuclear translocation of NFB and activation of NFB-mediated gene transcription .
A recent study revealed an unexpected connection between TNF signaling and myogenin on MuRF1 and atrogin-1 expression: TNF treatment causes upregulation of myogenin, MuRF1 and atrogin-1. Interestingly, a G-protein-coupled receptor blocks the TNF-mediated myogenin upregulation by activating Gi2 and the expression of muscle-specific ubiquitin ligases. However, the precise mechanisms of TNF-mediated myogenin regulation, the interplay with Gi2 and the implications for muscle wasting are still far from fully understood.
Taking Care Of Your Child
Itâs hard when your child loses strength and canât do the things other kids can do. Muscular dystrophy is a challenge, but it doesnât have to keep your child from enjoying life.
There are many things you can do to help them feel stronger and get the most out of life.
- Eat right. A healthy, well-balanced diet is good for your child in general. Itâs also important for helping them stay at a healthy weight, which can ease breathing problems and other symptoms. If itâs hard for them to chew or swallow, talk to a dietitian about foods that may be easier to eat.
- Stay active.Exercise can improve your childâs muscle strength and make them feel better. Try low-impact activities like swimming.
- Get enough sleep. Ask your doctor or therapist about certain beds or pads that can make your child more comfortable and rested.
- Use the right tools. Wheelchairs, crutches, or electric scooters can help your child if they have trouble walking.
The disease will most likely have a big impact on your family. Remember that itâs OK to ask a doctor, counselor, family, or friends for help with any stress, sadness, or anger you may feel. Support groups are also good places to talk to other people who have lived with muscular dystrophy. They can help your child connect with others like them and give you and your family advice and understanding.
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Lack Of Sexual Activity And Penile Atrophy
Research has shown that your penis has a bit of a use it or lose it mentality to health.
To have healthy, regular erections that are consistently hard and the same size, its essential to actually get an erection on a regular basis .
You remember how prostate cancer patients experience permanent shrinkage due to lack of use while their soft tissue is healing?
Well the same thing can happen to you, if you dont get it up on a regular basis.
The goal here is to keep the soft tissue soft. Infrequent erections mean that the soft tissue hardens into collagen, reducing the ability to fill and trap blood and thus, get hard.