Sarcopenia


Sarcopenia is an age-related, involuntary loss of skeletal muscle mass and strength. It begins as early as the fourth decade of life, and evidence suggests that skeletal muscle mass and skeletal muscle strength decline in a linear fashion. Given that muscle mass accounts for up to 60% of body mass, pathological changes to this important metabolically active tissue can have profound consequences on the older adult. These consequences are often severe, as the strength and functional declines associated with sarcopenia can in turn contribute to a number of adverse health outcomes, including loss of function, disability, and frailty.

Type I and II muscle fibers

Skeletal muscle consists of two types of fibers. Type II (fast fibers) have a higher glycolytic potential, lower oxidative capacity, and faster response as compared to type I (slow fibers). Type I are known as fatigue-resistant fibers, due to their greater density of mitochondria, capillaries and myoglobin content. Most muscles consist of both types of fibers except for postural muscles which consist of type I fibers only. During slow, low intensity activity, most strength generated comes from type I fibers, while in high intensity exercise strength comes from both. With age, atrophy affects mainly type II fibers. The resulting muscle weakness is a consequence of the degradation of myofibrils, which is catalyzed by ubiquitin ligases that target different components of the contractile apparatus for proteasomal degradation. By contrast, loss of endurance results from the breakdown of mitochondria via autophagy.

Muscles changes in aging

The physiological and morphological changes in skeletal muscle with advancing age are characterized by overall declines in size and number of skeletal muscle fibers, mainly the type II or fast-twitch muscle fibers, and a marked infiltration of fibrous and adipose tissue into the skeletal muscle. In addition, satellite cells, the skeletal muscle precursor cells that reside in a quiescent state in association with myofibrils, likely also undergo important aging-related changes. These satellite cells are activated and begin the process of skeletal muscle repair and regeneration in response to the stress of heavy muscle use or through traumatic events such as injury. In the skeletal muscle of older adults, the satellite cell content is reduced, most specifically in the type-II skeletal muscle fibers.

There are many causes of sarcopenia - different patients have different causes and often more than one cause. Sarcopenia can be induced by chronic diseases, insulin resistance, poor nutrition, endocrine system malfunctions, and cancer treatment.

Diagnosis

There are multiple techniques available to measure muscle mass ranging from chemical composition (total body potassium/nitrogen) to imaging (computed tomography (CT), magnetic resonance imaging (MRI), and dual-energy x-ray absorptiometry (DXA to less technically challenging methods such as bioelectrical impedance analysis (BIA), anthropometry or hydrostatic weighing. DXA of course is dual-energy X-ray absorptiometry used to measure bone density in common checks for osteoporosis. Here it is used to estimate body mass in limbs. Availability and expense are factors in choosing a diagnostic technique; in clinical practice, doctors most often use DXA. There is no definitive biological marker of sarcopenia, but there are a number of markers that are associated with it, including adipokines, cytokines, antioxidants, evidence of oxidative damage, and apoptosis.

The following measurements suggest sarcopenia:

Walking speed under 0.8 m/sec
BIA readings of lean body mass:
Men - less than 8.50 kg/m2, Women - less than 5.75 kg/m2

ALMH (appendicular lean mass) is a parameter analogous to BMI but for limbs rather than for the whole body. (ALM)/height2)

Sarcopenia is suggested if ALMH is
Men - less than 7.26 kg/m2, Women - less than 5.45 kg/m2

Here's another proposed definition: similar to how osteoporosis is defined by a bone density more than two standard deviations below average density in young adults, so sarcopenia is defined by loss of skeletal muscle mass two standard deviations below sex-specific normal values for young adults. However there is no universally agreed upon definition.

Muscle loss in the setting of obesity is known as sarcopenic obesity.

Dynapenia is not the same as sarcopenia. Dynapenia refers to loss of muscle strengh in older people that is not caused by neurological or muscular disease and does is not necessarily connected with a loss of muscle mass. Both dynapenia and sarcopenia are risk factors for disability.

Prevention

Older adults who practice physical activity and stick to a healthy diet tend to positively impact satellite cell dysfunction, neuromuscular junction decline, and mitochondrial biogenesis. Experts also recommend that measures of muscle mass, muscle strength, and/or functional performance be taken for many people and the results collected. This accumulation of population data will help to facilitate the operationalization and validation of a sarcopenia diagnostic screening methodology that can be used in clinical trials, and integrated into the practice of geriatric medicine. An example would be correlating walking speed with a loss of muscle mass.

Treatment and potential medicines

As diet changes with age, seniors often consume less protein, Vitamin D, and long-chain polyunsaturated fatty acids, deficiencies of which have been linked to decreased muscle function. One possible solution to sarcopenia lies within vitamin D supplementation, which has been demonstrated to increase muscle strength and performance. Physical activity can forestall and potentially reverse sarcopenia. While the loss of strength and endurance occurs across the age span, training helps muscle meet the demands of increased activity by increased enzymatic protein production, capillary density for higher muscle metabolic demand and contractile protein production to allow a greater contraction tension.

A recent study concluded high-intensity, stretch-shortening contractions (SSCs) are beneficial in slowing or reversing the progression of sarcopenia. This type of resistance exercise is familiar to most therapists and exercise coaches.

No medicines have been approved for sarcopenia in the US or EU, but some are in development. A ghrelin-like agent, capromorelin, increased lean mass, tandem walk, and stair climb in older sarcopenic individuals. Selective androgen receptor molecules (SARMs), such as enobosarm, have shown similar effects. An activin II receptor antibody, bimagrumab, also increased quadriceps strength and physical performance. A cardiological drug, perindopril, improved distance walked in older people. Muscle troponin activators, such as tirasemtiv, amplified the response to motor neuron input, increased muscle power, and improved muscle fatigability. Finally, glitazone, an oral antidiabetic, could have possible anabolic effects in the muscle tissue as well.

Osteosarcopenia

Osteosarcopenia isn’t a disease; it’s a syndrome. (A syndrome is a cluster of symptoms and signs, which may or may not be due to one or more diseases.) Osteopenia is low bone density, and sarcopenia is loss of muscle mass and strength. When people get them both, the resulting impact on the quality of life can be worse than either one produces by itself. The syndrome produces falls, fractures, and disability and increases the probability of death This syndrome affects the elderly, but the prevalence is unknown partly because only recently has it been recognized.

The causes are unknown, too, and it is probably true that there are multiple causes in any individual and osteosarcopenia in one individual may be due to different factors than osteosarcopenia in another person. Genetic factors could be partly responsible as well as lifestyle (activity, exercise), other co-morbid conditions, and medications taken.

Bone and muscle closely interact with each other, Fat infiltration of bone tissue happens often when elderly people lose bone mass and muscle tissue. A better understanding of how muscle and bone interact with each other may lead to effective therapies.

With no definitive cause the treatments at this point are pragmatic and common sense: exercise and nutrition. Perhaps in the future pharmacological therapies will be developed. SARMs may be a treatment for osteosarcopenia some day.

Related: Vaginal Atrophy

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