Inflammation in Degenerative Disease
degenerative disease is the body at war with itself – where cells, tissues and organs deteriorate over time as the body attacks its own systems. Degenerative diseases greatly impact a person’s quality of life. These diseases involve complex interactions between ageing, lifestyle choices and a person’s family history, making it incredibly hard for scientists to understand what causes them, and how to treat them. But while we struggle to find the trigger for degeneration, we do know one event that worsens degenerative disease: chronic inflammation, where a normal part of the body’s healing system goes awry and becomes a long-term, destructive condition.
What are degenerative diseases?
The changes of normal ageing also come with an increased chance of developing a degenerative condition. These can begin in any system of the body, from the muscles and skeletal system to the brain and nerves.
Our muscles produce the force we need to act and function, controlling every movement we make. Degenerative diseases affecting our muscles result in weakness, wasting and eventual paralysis in specific muscle groups, eventually spreading to the rest of the body. Skeletal muscles are strong tissue cords connected to and moving the bones; smooth muscles are responsible for involuntary movements and reside in the intestines, stomachs and other organs; and cardiac muscles consist of stretched out fibres that are found in the heart for contraction. Common degenerative diseases of the muscles include:
- Polymyositis: a treatable and rare condition, where the muscles become inflamed and weak. Causes difficulty swallowing, a chronic cough and problems with falling. Predominantly seen in women over the age of 20.
- Dermatomyositis: another rare condition that has no cure, more often seen in women. Presents as a rash, muscle weakness, and inflammation and pain in the muscles.
- Muscular dystrophy: symptoms vary depending of the muscle groups affected, with most people losing the ability to walk. An inherited disorder, it sometimes appears in childhood, though other forms can appear in middle age and later. Can have mild symptoms and slow progression of degeneration, or severe symptoms that become disabling.
- Myasthenia gravis: a neuromuscular disease caused by lost communication between nerve cells and the muscles. Reduces the ability of muscles to contract, leading to weakness of skeletal muscles.
- Amyotrophic lateral sclerosis: a neurodegenerative disorder impacting muscles needed for voluntary movement, and nerve cells in the brain and spinal cord. Diagnosed at ages 40-70, with no cure or treatments. Life expectancy is only a few years after diagnosis.
- Rhabdomyolsis: causes of the condition include trauma, infection and inflammation, and is a muscle disease causing breakdown of skeletal muscle. Results in released myoglobin – storing oxygen in our blood – into the bloodstream, resulting in kidney damage.
- Cardiomyopathy: a progressive disease affecting muscles of the heart.
Degenerative diseases of joints and bones are a result of chronic wear and tear over time. The most common degenerative joint disorders are osteoporosis and osteoarthritis. Osteoporosis is a condition where the bones lose density and are much more likely to fracture. This can cause a loss of height, changes in posture, impaired walking, and severe back pain. The disease can go undetected for many years and is likely to be diagnosed after the first fractures begin occurring. On the other hand, osteoarthritis is a painful, degenerative joint disease and develops in joints that are injured by repeated overuse. Although these two diseases sound similar, the diagnosis, treatment and symptoms are completely different.
Finally, neurodegenerative diseases are incurable and debilitating conditions that result in the loss or death of nerve cells in the central nervous system (the brain and spinal cord) and the peripheral nervous system (nerves communicating between body parts and the central nervous system). When this cell death occurs in a specific part of our brains or a population of brain cells, we get different diseases and different symptoms. While there is an absolute plethora of neurodegenerative conditions, some of the more common are:
- Dementia: an umbrella term for a range of disorders that change specific ‘thinking’ regions in the brain, the most common being Alzheimer’s disease. Dementias can cause memory loss; behavioural and personality changes; and interfere with a person’s everyday activities, greatly impacting quality of life.
- Parkinson’s disease: manifesting as tremors, posture instability and rigidity, Parkinson’s is the second most common neurodegenerative disease, with symptoms beginning gradually before increasing in severity.
- Huntington’s disease: an inherited disease, symptoms start at 30-50 years of age. Symptoms can include memory lapses, depression, fidgeting or jerkiness, problems swallowing, difficulty moving and clumsiness.
- Multiple sclerosis: caused by the immune system attacking the ability of neurons to communicate. Deeply linked to inflammation, the disease causes progressive loss of movement.
- Amyotrophic lateral sclerosis: mentioned above as a degenerative disease of the muscles, we now know that this disorder begins in the cells of our central nervous system before spreading outwards to our muscles.
There are many factors and disease pathways that neurodegenerative disorders share, and we still don’t understand why specific parts of our brains degenerate and create distinct symptoms. Recently, it has been thought that targeting inflammatory pathways activated in degenerative disorders, we may ease symptoms of these disorders or slow degeneration.
What is inflammation?
Inflammation is a complex process that the body undergoes in response to harm – such as damage to our cells or tissues, irritants and toxins – and is meant to be protective. Its function is to get rid of the initial cause of injury, and clear out damaged tissues. It can be classified as acute or chronic: acute being the very first immune response with increased movement of blood plasma and white blood cells into injured tissues, and chronic being where cells at the injured site begin to destroy and heal tissue at the same time. Signs and symptoms of chronic inflammation include:
- Chronic fatigue
- Sleeping issues
- Sudden weight gain or loss
- Changes in menstrual cycle
- Generalised pain
- Frequent infections
When inflammation occurs, many different cells of the immune system are involved. These release substances called inflammatory mediators, triggering more blood and more immune system cells to reach injured tissues. But you can always have too much of a good thing, and inflammation doesn’t always help the body; when the body fights against its own cells, it causes harmful inflammations that can become chronic.
How does inflammation interact with degeneration?
While chronic inflammation is not causative for degenerative conditions, it can greatly influence how quickly a disease progresses, the severity of symptoms, and the effectiveness of any treatments. Each of our body’s systems experience chronic inflammation in a slightly different way, and each degenerative disease has its own unique inflammatory profile.
Normally, there is tightly controlled crosstalk between muscles and our immune system. In disorders of muscular degeneration, this crosstalk is impaired, and inflammation required for muscle repair instead exacerbates muscle loss. Currently, chronically higher levels of inflammatory mediators are present, worsening muscular degeneration and the gradual loss of muscle mass. Inflammation in muscular degeneration can also lead to fibrosis – where tissue thickens and scars, further impairing the body’s efforts to repair muscles. Therapies targeting inflammation in muscular degeneration are focused on rescuing this secondary muscle damage caused by the condition.
In skeletal degenerative disease, the accumulation of inflammatory cytokines – molecules released from immune cells, responsible for immune regulation – interferes with pathways of repair in the body, leading to disease. This release inhibits the formation of new bone to replace damaged and injured bone. Inflammatory conditions can also disturb the balance between pathways responsible for removing mature tissue and bone formation. Though the loss of skeletal and muscular integrity is a normal part of ageing, it is increasingly apparent that inflammation has serious impacts on how rapidly this occurs.
Brain inflammation is increasingly seen to have a huge role in Alzheimer’s, Parkinson’s, forms of dementia and Amyotrophic Lateral Sclerosis. Normally, neurons – our major brain cells, sending and receiving information – create an immune response to trigger inflammation, functioning to clear debris and get rid of toxic or infectious agents. But the chronic activation of this response causes damage to nerve structures, impacting their ability to communicate in their environment and pass on the signals needed to maintain normal functions.
In degenerative diseases of the brain, we often see protein ‘clumps’ in post-mortem brain tissue. When these clumps form, the proteins that get stuck here lose their normal functions, becoming toxic to their environment. The body identifies the protein clumps as an invader, and goes to work initiating pathways of inflammation. In Alzheimer’s and Parkinson’s we now know that nearly every pathway of chronic inflammation is activated at later disease stages when the number of these protein clumps is highest. Yet the classic example of a relationship between inflammation and degeneration is the chronic disease multiple sclerosis. Classed as a chronic inflammatory disease of the central nervous system, it features extensive inflammation that results in damage to the large signal-sending fibres in the brain. The inflammation creates lesions that not only increase the release of inflammatory mediators, it also brings immune system cells to the affected regions that further worsen disease progression.
While scientists continue to work towards treating degeneration in our body’s systems, what can we do to decrease our risk of inflammation worsening these diseases?
Risk factors for inflammation and degenerative disease
Lifestyle has a huge impact on inflammation and promoting a low-level inflammatory response. Poor diet, low activity and consumption of alcohol, tobacco and other substances impacts all of the metabolic processes of our bodies. Age elevates the levels of inflammatory molecules our body releases, and can be due to dysfunction of cell functions, accumulation of toxins and age-related factors. Obesity is linked to fat tissue acting as an organ itself, releasing inflammatory mediators. A person’s weight can be proportional to the amount of pro-inflammatory cytokines secreted. Diets high in saturated or trans-fats, or refined sugars, also encourage the production of pro-inflammatory substances, and this is even greater in those who are overweight. Smoking reduces the production of anti inflammatory molecules, while simultaneously increasing inflammation, as does alcohol. Studies have shown that low sex hormones can also suppress the production of pro-inflammatory markers, whilst maintaining the balance of these hormones can reduce the risk of inflammatory disease. Finally, stress and sleep disorders increase the release of inflammatory molecules and are two of the major independent risk factors of chronic inflammation.
How do reduce the impact of chronic inflammation on degenerative disease?
Sufferers of degenerative disease need individualised and frequent medical care from specialists; doctors who have experience in specific diseases and who have knowledge of the latest available treatments. Though we have no cures available for the vast majority of degenerative conditions, there are dietary and lifestyle changes that reduce the triggers of inflammation, easing the severity of some symptoms.
Weight loss is one of the greatest ways that can help reduce inflammatory conditions and ease secondary symptoms. Being overweight comes with a slew of risk factors for chronic inflammation, and losing weight is conversely shown to reduce levels of inflammation in our bodies. Physical exercise, independent of weight loss, can also lower molecules and cytokines that trigger inflammation.
Yet weight loss and exercise are only a small aspect of reducing inflammation. One of the greatest mediators of our body’s inflammatory processes is our diets; dietary changes can have huge benefits in moderating the severity of a chronic inflammatory condition that can exacerbate degeneration:
- Fruits and vegetables high in antioxidants, polyphenol and other anti-inflammatory compounds can protect against inflammation. This includes cabbage, cauliflower, broccoli, apples and blueberries.
- Nuts can reduce the risk of diabetes, a disorder that can cause secondary inflammation, particularly almonds and walnuts.
- Reduced saturated and trans-fats can promote inflammation, while omega-3 polyunsaturated fats are anti-inflammatory. ‘Bad’ fats can be found in processed foods, baked goods and vegetable oils; ‘good’ fats can be found in fish and seafood, nuts and seeds, and plant oils. Fish oil is one of the richest sources of omega-3 fats.
- Mung beans are known for anti-inflammatory effects, being high in flavonoids – in itself, rich in anti-oxidants.
- Fiber and tea polyphenols – found in black and green – can lower levels of inflammatory molecules.
- Curcumin – a part of turmeric – has been shown to improve inflammatory diseases, with ginger also having anti-inflammatory benefits.
- Micronutrient intake is one of the most effective anti-inflammatory dietary factors, encompassing vitamin D and E, selenium, zinc and magnesium. Vitamin D in particular lowers anti-inflammatory activity, while vitamin E, selenium and zinc act as anti-oxidants.
As well as natural interventions and lifestyle changes, there are a number of conventional prescription medications that can combat chronic inflammation. Often, these are used already to treat other disorders that consist of secondary inflammation. Statins lower the levels of ‘bad’ cholesterol and its production inside the liver. They are also anti-inflammatory and reduce circulating mediators of inflammation. Corticosteroids are steroid hormones that prevent inflammatory mechanisms; in particular, glucocorticosteroids are prescribed for conditions such as asthma, lupus and arthritis. Metformin also reduces the circulation of inflammatory molecules and is used to treat low-level inflammation in type II diabetes. Finally, non-steroidal anti-inflammatory drugs (NSAIDS) – like ibuprofen and aspirin – inhibit the substances that can worsen inflammation, and ease the pain caused by chronic inflammation in conditions such as arthritis.
Yet it isn’t as easy as finding some medications and dietary changes. Chronic inflammation and degenerative diseases are complex, and it is important to remember that treatments can have unknown interactions with one another. Overall, the safest course of action is to:
- Eat more anti-inflammatory foods such as whole grains; vegetables and fruits; cherries and berries; and fatty fish and avoid sugars; refined carbohydrates; high glycemic foods; trans fats; and hydrogenated oils.
- Control the intake of antibiotics and NSAIDS as well as other medications that can harm the microbiome. While these can mediate inflammation, it is important that they are only used for these conditions under a doctor’s recommendation.
- Sleep! A good night’s sleep is critical for growth and sex hormones that rebuild damage in the body.
- Avoid stress; chronic stress can impair the body’s ability to control inflammatory responses. Yoga, meditation, and counselling can help ease stress-induced inflammation.
- Exercise is critical for staying at an optimum weight but can also lower the risk of cardiovascular disease and strengthening muscles and bones.
What’s the final word?
Many inflammatory disorders have no cure, as is the case with even more degenerative disorders. Symptomatic therapy is the only avenue that has consistently been shown to treat these diseases, and what is needed is an army of allied health professionals. If suffering from a chronic degenerative disorder and subsequent inflammation, the underlying causes need to be addressed with nurses, physiotherapists, specialists, dieticians, and primary care physicians. Unfortunately, there are no effective tests for most degenerative conditions or inflammatory disorders until symptoms are clearly visible – so it is vital to continue with regular doctor’s appointments to identify changes to your normal wellbeing.
The good news is that inflammation in degenerative disorders provides a target to slow disease progression and degeneration of affected tissues. Anti-inflammatory therapies may have huge potential for treating degenerative disease, and future research is focusing on how to harness anti-inflammatory pathways to ease secondary symptoms.
Any chronic condition can be difficult and heartbreaking to deal with, and often we do not have the tools to cure or even effectively treat these disorders. Yet there is hope: by identifying secondary impacts such as inflammation, scientists can target these pathways to improve quality of life and ease symptoms of these debilitating conditions.