Objective Nutrition

Sarcopenia: a new public health concern


OBJECTIF NUTRITION 93 (SEPTEMBER 2009)
Christelle Guillet, Stéphane Walrand, Yves Boirie,
Human Nutrition Unit, Mixed Research Unit (UMR) 1019, Department of Clinical Nutrition, French National Institute for Agricultural Research (INRA)–University of Auvergne, Clermont-Ferrand, France






From the age of fifty, both the quantity and quality of skeletal muscle begin to fall. Such sarcopenia is characterised by a reduction in muscle mass and strength, leading to a gradual withdrawal from everyday activities and an as-yet poorly evaluated risk to the health of the individual. Changes in the balance between the processes whereby the proteins building muscle are synthesised and degraded may explain this phenomenon: in the elderly, a decline in the activation of muscle protein synthesis by nutrients leads in the long term to a marked loss of proteins.

As we age we lose muscle, an inevitable physiological process known by the scientific term “sarcopenia”, from the Greek meaning “poverty of flesh”. The accumulated loss of muscle mass reaches 40% between the ages of twenty and eighty, but its impact has not been clearly identified due to the lack of clear definition and simple measurement of muscle mass and function.

The diagnosis of sarcopenia remains difficult and must be established on the basis of criteria currently being developed by several groups of international experts. These criteria take into account both muscle mass, measured by biophysical methods of varying degrees of complexity, and function, assessed directly by strength or indirectly by simple performance tests (e.g. walking speed).

ETIOLOGY OF SARCOPENIA

The factors responsible for muscular ageing (Figure 1) include changes in muscle structure, in the control of muscle contraction by the nervous system and in the secretion and regulation of hormones, leading to a reduction in muscle strength and ability to contract. External causes — sedentary lifestyle, unbalanced diet, the onset of many diseases, and the use of medication — also contribute to an age-related decline in muscle function.



BOX 1: CAUSES OF MUSCLE LOSS WITH AGEING

• Changes in muscle structure

Age-related changes in muscle mass are associated with changes in muscle structure, particularly fibre composition. The two types of fibres essentially comprising skeletal muscles do not have the same mechanical and metabolic properties. With their slow contraction speed, type I or red fibres generate little strength but are well-suited for endurance.

The quickly-contracting type II or white fibres enable a fast contraction speed but have little resistance to fatigue. Sarcopenia is thought to be largely due to the atrophy of type II muscle fibres. The density of type I fibres, which is less affected, may even be greater in the muscles of the elderly. These changes translate into a reduction in muscle strength despite the maintenance of a certain level of endurance.

• Changes in the control of muscle contraction

In older muscles, the loss of fibres may be due to either irreversible changes or a denervation of the fibres. Neurons, which are directly connected to the muscle fibres, control muscle contraction via a nerve impulse, the whole process being called motor unit.
 
Several studies have highlighted a progressive loss of neurons in older animals. This phenomenon, which is associated with lower muscle stimulation, plays an important role in the muscular dysfunction and atrophy observed with age. Nonetheless, the motor units remain active in older muscle, despite numerous changes in quality and quantity. As such, physical exercise could make it possible to slow muscle ageing.

• Changes in the control of muscle mass

Muscle size, function and composition depend on the quantity and quality of the proteins building it, changes to which are in large part linked to variations in the synthesis and degradation of the proteins within this tissue. In fasting state, the body draws on the necessary amino acids in the muscle, particularly for the production of glucose. The degradation of the proteins prevails and the quantity of proteins in the muscle declines. Following a meal, the amino acids resulting from dietary proteins are used this time for muscle protein synthesis. As synthesis overtakes degradation, the quantity of proteins in the muscle increases, compensating for the loss of proteins during fasting. Several studies indicate that the activation of muscle protein synthesis by a meal appears to be affected by age. Other factors may be involved, such as the inappropriate production of certain hormones and inflammatory factors (androgens, growth hormone, insulin resistance, hypercortisolism, and cytokines) and the lack of physical activity.




BOX 2: CONSEQUENCES OF MUSCLE LOSS

PREVENTION OF SARCOPENIA

• Prevention with nutrition

Protein intake is the major nutritional determinant activating the synthesis of proteins, with the increase in amounts of amino acids in the bloodstream (hyperaminoacidemia) resulting from the digestion of dietary proteins. These substrates are able to stimulate the synthesis of muscle proteins as well as decrease degradation. Amino acids also activate their own degradation, limiting their excessive accumulation in the blood. It is therefore illusory to hope to increase protein mass greatly by administering very high quantities of proteins. However, protein intake declines with age, largely due to age-related anorexia, poor oral health, poly-medication, restricted diets and socio-economic reasons. Furthermore, the recommended protein intake of 0.8 g/kg/day, determined for young people, is thought to be insufficient for healthy elderly subjects, for whom dietary intakes should be more around 1 to 1.2 g/kg/day. An increase in protein intake may be a mean of limiting loss of muscle proteins. However, attempts to improve muscle mass with protein supplements have proven to be unsuccessful, probably due to the involvement of other factors associated with these disorders (energy inputs, change in the digestion and metabolism of amino acids, inflammation and physical inactivity).

Several studies have shown that in older muscle, although the synthesis of proteins is largely unresponsive to the effect of a meal, a quick and significant increase in aminoacidemia is able to activate muscle protein synthesis, and must therefore be considered in the prevention of sarcopenia. Postprandial aminoacidemia depends not only on the amino acid content or composition of dietary proteins, but also on the ability of the intestine and liver to retain the amino acids resulting from the intestinal digestion of proteins: on average 50% of the amino acids digested are retained by the splanchnic tissues (a figure that varies greatly from one amino acid to another). This physiological process increases with age. Therefore, if the splanchnic region retains more amino acids in elderly subjects (as in the case of an inflammation where the production of proteins linked to the inflammatory reaction is increased), the flow and availability of diet-derived amino acids for the surrounding tissues, including muscle, could be reduced. This might explain the poor response of muscle protein synthesis to the ingestion of a meal.


Considering all these aspects, nutritional strategies have been envisaged in order to limit muscle loss. A serie of experiments has shown that, in the elderly, when 80% of the daily protein intake is consumed at the midday meal, the protein gain is better than when shared across four meals. Nonetheless, although this distribution of protein intake appears in theory to be more anabolic in the elderly, it remains difficult to implement. The speed at which dietary proteins are absorbed may play a crucial role in the rate at which amino acids appear in the bloodstream and therefore enable better stimulation of muscle protein synthesis. This hypothesis has been tested by studying the impact of two major milk protein fractions, caseins and whey proteins, in the young and elderly. These two milk fractions do not exhibit the same behaviour in the digestive tract, particularly in the stomach. Whey proteins could be considered as “fast” when they are rapidly digested into the stomach due to their solubility at acid pH, and then absorbed in the duodenum. In contrast, caseins could be considered as “slow”, as they precipitate into the stomach, are released slowly in the small intestine, and are absorbed more slowly and sustainably over several hours. The “slow or fast” nature of a protein continues when the proteins are given into a complete meal. In the elderly, the consumption of fast digested proteins proves to be more beneficial to the increase in protein mass.

Finally, the administration of supra-physiological quantities of certain amino acids, such as leucine, makes it possible to stimulate muscle protein synthesis.

• Prevention with hormones

Certain hormones promote muscle gain. They are commonly called anabolic hormones. The secretion of some of them, such as testosterone, growth hormone (GH) and insulin-like growth factor (IGF-1), declines with age, which could explain muscle loss. Replacement therapies have been envisaged and tested, and some have yielded highly encouraging results. However, their secondary effects must be taken into consideration and their contraindications observed.

• Prevention with exercise

High-resistance exercise rapidly improves muscle quality and increases mass only at a later stage. Many research studies demonstrate that resistance exercise increases muscle protein synthesis, mass and strength. Physical activities involving endurance increase muscle protein synthesis but have little effect on increasing muscle strength: muscle loss continues even in the most active elderly subjects. Nevertheless, they make it possible to increase aerobic capacity and muscular adaptation, and contribute to improvement in balance, appetite and numerous age-related risk factors.


BOX 3: NUTRITIONAL PREVENTION OF SARCOPENIA

CONCLUSION

An appropriate diet, based on the daily distribution of protein intake or the use of rapidly digested proteins, combined with regular physical activity and/or hormonal treatments, could prevent sarcopenia in the elderly.