Sarcopenia – a cornerstone of ageing in men and women - Cytoplan

Sarcopenia - a cornerstone of ageing in men and women - Cytoplan

The word sarcopenia comes from sarx meaning “flesh” and penia meaning “loss”, hence it is a term describing muscle loss. It is well documented that ageing is associated with muscle loss. This is both a double edge sword and a vicious cycle. When considering longevity, muscle has been referred to as the “Anti-ageing God.”

Muscle plays an essential role in maintaining wellness as we age, but as we age muscle mass declines. At the same time as muscle loss, we get an increase in adipose tissue, further contributing to loss of lean body mass percentage and subsequent physiological dysfunctions (discussed later). If muscle can be maintained more effectively throughout life and particularly in older generations, it can support healthy ageing and longevity. This blog discusses the importance of muscle health and how it can be maintained.

Ameliorating sarcopenia is important for all aspects of ageing in both men and women and BMI is a strong predictor in both genders. There are however a greater number of factors that may influence muscle mass more significantly in men including strength, power, and availability of testosterone.1 Hence, interventions that support healthy muscle mass in men throughout life can contribute to healthy ageing and protection against chronic disease.

Why is muscle so important?

Firstly, muscle is obviously essential for normal movement and strength. Healthy muscle supports activity throughout life, helps to prevent sedentary lifestyles and immobilisation. Just from a practical, functional point of view it contributes to ongoing wellness. Additionally, healthy lifestyles in older age (maintaining activity and optimal nutrition) contributes to healthy muscle, and if this cycle can be maintained it supports optimal wellness.

The maintenance of strength and fitness is also fundamental to reducing the risk of frailty and falls. A fall can be a huge risk in older age, particularly increasing the risk of fractures. When people lose muscle mass they experience reduced strength, reduced balance, and poor blood sugar dysregulation (to name a few), hence the risk of a fall increases.2

Hip fractures, specifically, can be significant triggers of age-related decline. The subsequent immobility, need for invasive surgery and hence increased risk of infection as well as need for optimal nutrition to support recovery, all contribute to a decline of health following a fall. The gerontologist Dr Gabrielle Lyon states that a fall at over 65 years of age leads to an increased risk of all-cause mortality.3

Muscle, however, is more than just an organ for movement and structure, it is a site of high metabolic activity and is fundamental for physiological processes, such as;

Insulin resistance

Skeletal muscle is the initial site of many metabolic conditions including obesity, type 2 diabetes, metabolic syndrome and even Alzheimer’s disease. This is because it is fundamental for insulin sensitivity.4

It is essential for glucose clearance and is responsible for over 80% of glucose uptake after the consumption of a meal. Insulin resistance is caused by the desensitisation of muscle to the insulin released by the pancreas to elicit glucose uptake, leading to elevated blood glucose levels. These elevated glucose levels are then consequently associated with the metabolic conditions mentioned above. Incidentally, skeletal muscle insulin resistance can appear decades before the onset of β-cell failure and symptomatic type 2 diabetes.4

As the principal site of insulin-stimulated glucose uptake, skeletal muscle is also considered the primary driver of whole-body insulin resistance. It is thought that insulin resistance starts in skeletal muscle long before other areas of the body. Hence skeletal muscle should be an important targeted for supporting insulin sensitivity.3,5

Endocrine organ

Skeletal muscle is also involved in communication with other organs of the body and therefore could be considered to have endocrinological properties. Muscle has the ability to produce myokines – cytokines produced by skeletal muscle in response to exercise which allow crosstalk between muscle and other organs including brain, liver, gut, pancreas, vascular bed and skin.6,7

There is still much needed research into the effects myokines have on other organs, but they have been shown to be beneficial for cognition, lipid and glucose metabolism, bone formation, endothelial cell function, skin structure and also stimulate the browning of white adipose tissue aiding the utilisation of fat for energy.7

Sarcopenia (muscle loss)

We begin to lose muscle mass from the age of 30 every single year. This accelerates later in life, especially in our 60s and onwards, until there is significant muscle loss in our 70s/80s and beyond, where sarcopenia has kicked in and humans become very frail.3

Anabolic resistance

When we are young, we are highly anabolic and have a great capacity to gain muscle, this continues until around the age of 30 when we begin to become anabolic resistant. Anabolic resistance is where there is a decrease in efficiency of skeletal muscle to recognise and utilise dietary protein, so stimulation of tissue is less. We can therefore find it much more difficult to gain muscle and the muscle needs greater stimulation to be able to grow or be anabolic.3,8

Unfortunately, this period in our lives is often when we are becoming more sedentary than in earlier life, so we can enter a perfect storm. Our bodies require a higher level of training to stimulate muscle growth but due to family and careers it may be a time when our activity begins to decline leading to further loss of muscle. Anabolic resistance is a hall mark of ageing, and a focus on muscle hypertrophy (muscle building) is fundamental to supporting health into old age.

Factors that can affect anabolic resistance include:

• Muscle building capacity and strength in earlier life – as mentioned, we are highly anabolic in our early years. The more muscle we can build (muscle hypertrophy) during this time, the more we are able to maintain or further grow as we age. This may now not be modifiable but demonstrates the importance of activity in children, which is currently in decline.

• Obesity – Skeletal muscle is affected by obesity, where the ability for muscle gain appears to be blunted, and therefore hypertrophy is more difficult – also see IMAT below.

• Inflammation – blunts skeletal muscle activity and is also strongly associated with obesity. High inflammation may also lead to pain and loss of function in the muscle, thus reducing movement, and making hypertrophy more challenging.

• Level of activity – Exercise is a potent stimulus of muscle gain, therefore activity and more importantly, direct training are fundamental to maintaining muscle.

• Protein intake – As we age, a larger amount of protein, particularly the amino acid leucine, is required to stimulate hypertrophy. Recommendations differ but approx. 0.8-1g/kg body weight daily intake of protein is required to stimulate muscle gain.3,8

Infiltration of intramuscular adipose tissue (IMAT)

Describes the situation when fatty tissue replaces muscular tissue within the muscle itself. This is associated with loss of strength and muscle contractility. If you could see the muscle, it would look like a marbled steak. IMAT reduces metabolism, glucose disposal, contractile function and the ability to repair. However, there is debate as to whether the real culprit is muscle loss and IMAT an innocent bystander or if it is a driver of muscle loss. What is known, is that if IMAT is present, there is a greater risk for both muscle loss and insulin resistance, leading to the onset of other diseases.9,10

Mitochondria

The mitochondria are the powerhouses of the cell and are responsible for regulating the metabolic status of skeletal muscle. As active muscle is highly metabolic, the status of mitochondrial function is critical to the contractility and anabolism of muscle.

Mitochondria are highly plastic and can adapt their volume, structure, and function in response to chronic exercise, disuse, ageing, and disease. We know that exercise is fundamental to muscle function and this is in part due the effect exercise has on the mitochondria.

A single bout of exercise initiates signalling to provoke increases in mitochondrial biogenesis (generation of new mitochondria), balanced by the onset of organelle turnover carried out by the mitophagy pathway (breakdown of old, worn-out mitochondria). This accelerated turnover ensures the presence of a high functioning network of mitochondria designed for optimal ATP supply, with the consequence of favouring lipid metabolism, maintaining muscle mass, and reducing apoptotic susceptibility over the longer term.11

Factors affecting sarcopenia

Sarcopenia has numerous causes including anorexia, inflammation, hypovitaminosis, immobilisation, HPA dysfunction and hypogonadism.

Hypogonadism – importance of testosterone

A predominant proportion of ageing older men have reduced levels of serum testosterone, due to a reduction is Leydig cells and an increase in testosterone binding to SHBG (sex hormone binding globulin).12,13 Low testosterone levels are associated with unfavourable body composition changes. Testosterone deficiency, along with lack of exercise and poor nutrition, may be among the modifiable contributors to sarcopenia. Testosterone treatment has been reported to have beneficial effects on muscle mass and function.

In human studies, testosterone treatment increased type I muscle fibres in both low and high concentrations, and type II muscle fibres in high concentrations. An increase in muscle fibre size is enhanced by increased protein synthesis, due to the high rate of re-utilisation of intracellular amino acid by testosterone.6,14

Other studies have demonstrated the importance of testosterone for muscle hypertrophy:

• One study reported that muscle mass was significantly associated with serum-free testosterone and insulin-like growth factor 1 (IGF-1) in relatively healthy, well-nourished elderly men (ref?)

• Another study showed that decreases in basal blood testosterone levels in ageing people may be associated with age-related declines in maximal voluntary neuromuscular performance capacity (ref?)

• Age, arm, and leg regional fat-free mass, serum testosterone, and the free testosterone index are significantly associated with arm and leg strength in generally healthy men15

HPA Dysfunction

It is important to consider that adrenal hormones such as cortisol and angiotensin II are catabolic in nature and have been shown to accelerate aged-induced muscle atrophy. Levels of both of these hormones increase with age. 6

Additionally, both testosterone and cortisol are produced from DHEA. If stress is increasing HPA activation, DHEA will be prioritised for cortisol to the detriment of testosterone production. Therefore, stress management is important in order to reduce HPA dysfunction and therefore the overproduction of cortisol.14

Inflammation

Inflammatory cytokines have been shown to prompt muscle wasting by stimulating protein catabolism and suppressing muscle synthesis and are negatively related to muscle strength and mass. Sarcopenia has shown to be associated with elevated serum CRP levels, a marker of inflammation. Studies have demonstrated that inflammatory cytokines activate many of the molecular pathways involved in skeletal muscle wasting leading to an imbalance between protein synthesis and catabolism. Hence, anti-inflammatory interventions are indicated.16

Supporting Muscle Hypertrophy

Exercise

Exercise is fundamental to so many aspects of health and should be incorporated into everyone’s life as part of a healthy lifestyle. Exercise increases GLUT4 uptake of glucose, which allows glucose into the cell without the need for insulin, thereby supporting insulin sensitivity which can be compromised in sarcopenia.17

In nature, we often see the phrase “use it or lose it” in practise. If muscle is not used it will not be sustained by the body. Therefore, when we are considering muscle maintenance (at a minimum) and hypertrophy (optimally), exercise should be at the forefront of any therapy.

As discussed, as we age our ability to put on muscle reduces and therefore the muscle needs more stimulation than it did when we were younger. So, although this may seem counter intuitive, we actually need to be doing more exercise than when we were in our teens and 20s as we get older.

Resistance training (e.g., weightlifting) is the most effective method to increase muscle mass. However, other forms of exercise such as high intensity interval training (HIIT) and cardio have are also an important part of maintaining health and muscle function.

If possible, the recommendations for supporting muscle hypertrophy should be followed although in the case of illness, injury or chronic disease this should be discussed with healthcare professional:3

• Resistance exercise 3-4 times a week, increasing resistance and/or volume as strength is gained to continue to stimulate growth.

• HIIT 1-2 times a week

• 150 minutes of cardiovascular exercise to maintain fitness every week.

Protein

Concomitant with exercise should be attention to protein intake. There needs to be adequate protein intake in order to stimulate hypertrophy; it is also important that the amino acid leucine is present and therefore a full spectrum of amino acids should be obtained.3 See Protein powders – a useful supplement to everyday diets for more detail.

Support testosterone levels

Certain nutrients are essential for the production of testosterone, and it has been shown that hypovitaminosis and/or anorexia can contribute to low testosterone as well as sarcopenia. So, nutrients involved in testosterone production must be prioritised.18,19

• Zinc – important for the maintenance and health of the testes as well as normal testosterone production. It also helps prevent testosterone from being converted into oestrogen. Suboptimal volumes of zinc appear to have a negative influence on serum testosterone concentrations as well as on seminal volume.

• Vitamin B6 – necessary for testosterone production and also supports adrenal function and neurotransmitter production.

• Vitamin D – a study confirmed previously observed positive associations between circulating vitamin D and total and free testosterone levels before and after administration of vitamin D supplementation. It demonstrated that vitamin D deficiency is associated with a significant reduction of testosterone. (ref?)

• Omega-3 fatty acids – help to maintain and increase testosterone levels. They also play an essential role in reducing inflammation and promoting normal cognitive function.

• Fenugreek – shown to increase total testosterone through an aromatase and 5α reductase inhibition, thereby blocking testosterone conversion to oestrogen and dihydrotestosterone, respectively. Increased total testosterone levels could potentially affect bioavailable testosterone concentrations, resulting in escalated delivery and use by muscle cells to enhance protein synthesis, thus positively influencing strength and body fat. The results of a present clinical study demonstrated the efficacy of 8-week treatment of Fenugreek (Fenu-FG) offered beneficial effects in terms of repetitions to failure in leg press, free testosterone levels and serum creatinine as compared with placebo.20

Inflammation

Reducing inflammation is also important as there is an association between inflammation and inflammatory conditions with low testosterone. Ways in which to reduce inflammation include:18

• Reduce foods high in omega 6 – e.g., farmed meats, dairy products and vegetable oils (such as sunflower and corn oils). These are high in the omega-6 fatty acid arachidonic acid or linoleic acid (precursor to arachidonic acid). Arachidonic acid can be converted to the pro-inflammatory prostaglandin PGE.

• Increase sources of omega-3 e.g., oily fish and flax, chia seeds and/or a supplement containing EPA.. Alpha linolenic acid is found in flax and chia seeds and dark leafy green vegetables and can be converted to EPA by the body. EPA is converted into anti-inflammatory prostaglandins.

• The ratio of omega-6 to 3 is very important – the majority of people are consuming too much omega-6 relative to omega-3 and therefore are often producing excess amounts of pro-inflammatory prostaglandins

• Curcumin – found in turmeric, has been shown to inhibit Cox-2 enzymes which produce inflammatory prostaglandins.

Adrenal Support

Moderating the stress response is essential for protecting against excess catabolic adrenal hormones and supporting testosterone production. Supporting adrenal function and stress management should be part of a plan to ameliorate sarcopenia. Adrenal support includes19:

• Nutrients such as vitamins B5, B6 and C, magnesium

• Adaptogenic herbs such as Rhodiola, ashwagandha and Siberian ginseng

• Relaxation techniques such as meditation and mindfulness, massage and yoga

Support mitochondrial function

Mitochondrial function is fundamental to the metabolic capabilities of muscle tissue. Therefore, to support muscle hypertrophy, mitochondrial function should be optimised. Nutrients that support mitochondria are:18

• CoQ10 (Ubiquinol) – utilised as a carrier in complex II of the electron transport chain . CoQ10 also has antioxidant properties and is found in high concentrations in the head and mid-piece of the sperm. It is considered to promote motility, foster sperm survival and provide optimal energy.

• Alpha Lipoic Acid – a coenzyme of pyruvate dehydrogenase and a-ketoglutarate; enzymes responsible for reactions involved in the breakdown of fat and carbohydrate within the mitochondria.

• Magnesium – binds to ATP and affects its structure, making energy more easily available.

All of the above nutrients are directly involved in metabolism reactions which occur in the mitochondria in order to produce energy. Any deficiencies of the above nutrients can affect the rate of energy production and will have a direct impact on the ability to produce sperm effectively.

There are other nutrients that are not directly involved in the chemical pathways of metabolism but are however important for energy production and maintaining mitochondrial function such as:

• L-Carnitine – plays a vital role in fatty acid metabolism, transporting fatty acids into the mitochondria to be converted into energy and again a deficiency can lead to reduced energy production. Carnitine concentrations have been found to be very high in the epididymis and testes. Studies which have compared fertile and infertile men have found that fertile men have statistically significantly more carnitine in their seminal sample than infertile men. Also, low levels of plasma carnitine are associated with infertility.

Key Takeaways

• Sarcopenia (muscle loss) – is associated with age and can increase the risk of falls and therefore fractures, surgery and infections. This can contribute to all cause mortality.

• Our ability to gain muscle (muscle hypertrophy) declines as we age and therefore it is fundamental to support muscle function in older adults. Resistance exercise coupled with optimal protein intake is an essential component of therapy to support muscle gain.

• Muscle isn’t just important for movement, it is also essential for normal glucose metabolism and sarcopenia is associated with insulin resistance and vice versa. In fact, muscle is the first organ to become insulin resistant and hence should be a target for metabolic conditions.

• Mitochondrial capability affects our ability to gain muscle and use of muscle function is essential for the generation of new mitochondria. Therefore, both exercise and mitochondrial support need to be considered. Nutrients such as CoQ10, B vitamin, Omega 3, magnesium and l-carnitine are important nutrients for this purpose.

• Levels of testosterone decline with age, however, further reductions can be exacerbated by HPA dysfunction or stress as well as nutrient deficiencies. Therefore, nutrients including vitamin D, zinc, B vitamins as well as stress management techniques are important if testosterone levels are decreased.

• Fenugreek is a herb that has been shown to support testosterone levels as well as muscle health.

• Inflammation may also contribute to both low testosterone and sarcopenia, hence anti-inflammatory interventions such as omega 3s, reducing omega 6 and utilising curcumin are important.