Regain Mobility and Physical Autonomy in Sarcopenia and Frail Patients: The Latest Evidence

ABSTRACT:

As more and more baby-boomers are now reaching retirement age the consequences of the current demographic shift will gain momentum during the next decade thereby exerting increasing pressure on the social systems of most Western Countries and especially on the health care sector. In this context the prevention of loss of autonomy and care dependency will be utmost importance. Geriatric medicine has to address these challenges and if it succeeds in doing it will not only increase the quality of life of the older population, but it will also strengthen the position of geriatric medicine among the medical disciplines.

The geriatric syndromes sarcopenia and frailty are both associated with accelerated functional decline and finally disability. Both share a complex etiology that includes numerous aging processes, lifestyle factors and negative effects of a large number of comorbidities. In the individual patient the contribution of these factors varies widely and therefore we should aim to provide our patients with more differentiated diagnosis of sarcopenia and frailty in the future. A future sarcopenia and frailty diagnosis would reflect the variable contribution of the different etiologies the latter being identified with the help of a series of biomarkers. This concept would serve as an example of personal geriatric medicine when we complement this diagnostic approach with a more differentiated therapeutic concept. In 2021 there is still no drug on the horizon that is likely to be approved for the therapy of sarcopenia or frailty within the next five years. Therefore we still have to stick to the established therapeutic standards which are exercise and nutrition. In recent years we have significantly expanded our knowledge on how we can optimize the positive effects of exercise and nutrition in patients that are affected by sarcopenia and frailty. However, open questions remain.

For example, we have to address specifically the dosing and timing of the aforementioned interventions, if we want to optimize the functional results in our patients. We still need more large, well-designed studies that reflect the heterogeneity of the older population. Only then we will able to establish the “perfect” intervention that is targeted,well-defined, accessible, efficient, affordable and most likely continuous. Although we have not achieved this ambitious goal yet, relevant progress has been made. This symposium will provide all participants with highly relevant up-to-date-information in this regard and it will be presented by excellent and highly respected experts in the field.

How hard and how often to exercise? - Intensity and efficiency of resistance training in older persons with sarcopenia and frailty

ABSTRACT:

Resistance training is one of the most efficient exercise modalities to counter muscle weakness in the aged (Beckwee, Delaere et al. 2019). It is therefore not surprising that this type of exercise has a major place in the recent World Health Organisation (WHO) guidelines for physical activity in older persons. In fact, the WHO published in 2020 an updated guideline on physical activity and sedentary behaviour (Bull, Al-Ansari et al. 2020). These guidelines include specific recommendations for older adults, older adults with chronic conditions (cancer survivors, arterial hypertension, type-2 diabetes and HIV) and adults living with disability (multiple sclerosis, spinal cord injury, cognitive disorders). Besides the recommendation for a sufficient weekly volume of aerobic physical activity, the WHO advocates at least on 2 days per week resistance exercise, this for all categories of older adults.

Typically, resistance training consists of performing muscle work against an external resistance. This external resistance can be produced by ones own body weight, using free weights or specific exercise machines. Moreover, resistance training can be performed at various modalities depending on the level of external load, the number of repetitions, the speed of movement, the number of series, and the duration of rest between the series. The external load is defined by the one repetition maximum (1RM, the maximal weight that can be moved/lifted only once), which needs to be assessed for each person individually. Resistance training using submaximal external load (i.e. 70-80% of 1RM) has been shown to be the best method to increase muscle strength in older persons. At this external load, one is able to perform about 8-12 repetitions before the exercising muscle is tired. Two to three series with at least 1 minute rest in between provides an ideal workout.

Although it is a very safe type of exercise, it is recommended to start the first exercise sessions at a lower external load (e.g. 50% of 1RM) and to increase progressively the external load by about 10% every 2-3 sessions until 70-80% of 1RM is reached. At least one day of rest between the exercise sessions is recommended. This progressive increase of external resistance will allow the older person to get acquainted with the exercises and will avoid excessive muscle soreness the days after the first exercise sessions. When performing this type of resistance training 2-3 times per week during 12 weeks more than 40% of strength gain can be obtained (Peterson, Rhea et al. 2010, Beckwee, Delaere et al. 2019). When performing resistance training with lower external loads, the number of repetitions should be increased. In fact, muscle failure at the end of the resistance exercise is considered as one of the key triggers for neuromuscular adaptation to occur (Van Roie, Delecluse et al. 2013, Arnold and Bautmans 2014, James, Nichols et al. 2021). However, resistance training at low external resistance will lead to a lower strength gain, even when performing a very high number of repetitions (Van Roie, Delecluse et al. 2013). Interestingly, resistance training also induces the production of myokines by the exercising muscle (Pedersen 2011). These myokines are small proteins that stimulate local autocrine and paracrine effects in the muscle. Many myokines are also released in the blood circulation exerting endocrine effects including energy metabolism (release of glycogen stores from the liver, increased lipolysis etc) and immune responses (Pedersen 2012, Laurens, Bergouignan et al. 2020). The latter contribute to an overall anti-inflammatory effect (Petersen and Pedersen 2005, Bautmans, Salimans et al. 2021, Mathot, Liberman et al. 2021). It is well known that ageing is often accompanied by the occurrence of a chronic low-grade inflammatory profile (CLIP) that accelerates the progression of sarcopenia and frailty. Thus, resistance training can combat both muscle weakness and chronic inflammation in the aged. The anti-inflammatory effect of resistance training is also related to the duration and intensity of the exercise, and proposing exercise at sufficient intensity is therefore necessary to stimulate this mechanism (Forti, Van Roie et al. 2016). In this lecture we will explain the recommended amount of resistance exercise and its dosing according to the aimed training effects and the clinical profile of older persons.

References:
• Arnold, P. and I. Bautmans (2014). "The influence of strength training on muscle activation in elderly persons: a systematic review and meta-analysis." Exp Gerontol 58: 58-68.
• Bautmans, I., L. Salimans, R. Njemini, I. Beyer, S. Lieten and K. Liberman (2021). "The effects of exercise interventions on the inflammatory profile of older adults: A systematic review of the recent literature." Exp Gerontol: 111236.
• Beckwee, D., A. Delaere, S. Aelbrecht, V. Baert, C. Beaudart, O. Bruyere, M. de Saint-Hubert and I. Bautmans (2019). "Exercise Interventions for the Prevention and Treatment of Sarcopenia. A Systematic Umbrella Review." J Nutr Health Aging 23(6): 494-502.
• Bull, F. C., S. S. Al-Ansari, S. Biddle, K. Borodulin, M. P. Buman, G. Cardon, C. Carty, J.-P. Chaput, S. Chastin, R. Chou, P. C. Dempsey, L. Dipietro, U. Ekelund, J. Firth, C. M. Friedenreich, L. Garcia, M. Gichu, R. Jago, P. T. Katzmarzyk, E. Lambert, M. Leitzmann, K. Milton, F. B. Ortega, C. Ranasinghe, E. Stamatakis, A. Tiedemann, R. P. Troiano, H. P. Van Der Ploeg, V. Wari and J. F. Willumsen (2020). "World Health Organization 2020 guidelines on physical activity and sedentary behaviour." British Journal of Sports Medicine 54(24): 1451-1462.
• Forti, L. N., E. Van Roie, R. Njemini, W. Coudyzer, I. Beyer, C. Delecluse and I. Bautmans (2016). "Load-Specific Inflammation Mediating Effects of Resistance Training in Older Persons." J Am Med Dir Assoc 17(6): 547-552.
• James, E., S. Nichols, S. Goodall, K. M. Hicks and A. F. O'Doherty (2021). "The influence of resistance training on neuromuscular function in middle-aged and older adults: A systematic review and meta-analysis of randomised controlled trials." Experimental Gerontology 149: 111320.
• Laurens, C., A. Bergouignan and C. Moro (2020). "Exercise-Released Myokines in the Control of Energy Metabolism." Front Physiol 11: 91.
• Mathot, E., K. Liberman, H. Cao Dinh, R. Njemini and I. Bautmans (2021). "Systematic review on the effects of physical exercise on cellular immunosenescence-related markers – An update." Experimental Gerontology 149: 111318.
• Pedersen, B. K. (2011). "Muscles and their myokines." J Exp Biol 214(Pt 2): 337-346.
• Pedersen, B. K. (2012). "Muscular interleukin-6 and its role as an energy sensor." Med Sci Sports Exerc 44(3): 392-396.
• Petersen, A. M. and B. K. Pedersen (2005). "The anti-inflammatory effect of exercise." J Appl Physiol 98(4): 1154-1162.
• Peterson, M. D., M. R. Rhea, A. Sen and P. M. Gordon (2010). "Resistance exercise for muscular strength in older adults: a meta-analysis." Ageing Res Rev 9(3): 226-237.
• Van Roie, E., C. Delecluse, W. Coudyzer, S. Boonen and I. Bautmans (2013). "Strength training at high versus low external resistance in older adults: effects on muscle volume, muscle strength, and force-velocity characteristics." Exp Gerontol 48(11): 1351-1361.

The perfect match – High protein supplementation, and exercise for the prevention and therapy of sarcopenia and frailty

ABSTRACT:

With age, declining function and whether it can be ameliorated is a basic question at the core of biologic gerontology. Skeletal muscle is a malleable tissue with ageing, and its mass and function of which, when lost, is termed sarcopenia. The recent designation with an International Classification of Diseases (ICD-10) code to sarcopenia by the World Health Organization represents a significant step towards recognizing the age-related loss of SMM and muscle function as a disease requiring healthcare intervention (Anker, Morley et al. 2016, Cao and Morley 2016). Maintaining skeletal muscle and function are important core health goals for ageing persons. Numerous guidelines have outlined why older persons need to maintain their skeletal muscle and muscle function, translating into a lower risk of mobility loss (Bhasin, Travison et al. 2020). At its most basic level, skeletal muscle protein mass is maintained by the simultaneous and opposing processes of muscle protein synthesis (MPS) and muscle protein breakdown (MPB). For net muscle mass accretion to occur, MPS must chronically exceed MPB, and the converse is also true for muscle loss. The two main stimuli for that affect MPS are protein ingestion and muscle loading. Without sufficient protein, or specifically without sufficient essential amino acid (EAA) intake, there is inadequate stimulation of MPS, and muscle mass will decline (Phillips 2017). Age-related mal- or under-nutrition, poor dentition, and declining appetite further limit older persons’ ability to obtain sufficient protein. We also know that older persons have what is known as age-related ‘anabolic resistance,’ which means that older persons’ muscles respond less well than younger ones to normally robust anabolic stimuli like protein ingestion and loading. Anabolic resistance and other reasons underpin an increased need for protein in older persons; however, it is important to realize that older persons can achieve similar stimulation of MPS with protein ingestion as seen in younger persons, but only when greater quantities of protein are consumed. The critical amino acid to stimulate MPS is leucine, and proteins rich in this, and other EAA, would be the most efficient way to achieve (for any given protein load) the most robust stimulation of MPS. A valid question is then, which types of proteins are the best at supporting a net protein balance? Clearly, it would be those proteins that have a high leucine, high EAA, and are easily digested. Viewed from this perspective, no other protein matches milk-dervied protein as a blend of casein (a slowly digested protein that suppresses protein breakdown) and whey (a rapidly digestd protein that stimulates protein synthesis) (Boirie, Dangin et al. 1997). The so-called slow and fast protein blend in most milks independently regulates MPS (Pennings, Boirie et al. 2011) and casein and whey as a mixture have the highest amino acid score when measured using the state-of-the-art digestible indispensable amino score (DIAAS) of and the highest leucine amino acid reference ratio (Rutherfurd, Fanning et al. 2015). These characteristics of milk proteins make them the most efficient source of leucine and EAA per g of protein nitrogen and thus good sources for at-risk populations such as the elderly and other clinical populations (Phillips and Martinson 2019).

Similarly to protein ingestion, without sufficient loading, muscle mass also declines. Muscle disuse/unloading-induced atrophy is likely due to a reduction in MPS and possibly an increase in MPB. Nowhere is this more apparent than when patients spend time on prolonged bed rest. In an older person, in whom muscle mass is declining due to sarcopenia and is experiencing age-related anabolic resistance, one can imagine that even periodic muscle disuse is a problem as it results in precipitous and rapid declines in muscle mass and function (Oikawa, Holloway et al. 2019). The loss of muscle in older persons means a loss of the tissue that constitutes ‘functional reserve’ and may explain why prolonged bed rest is so damaging to long-term health in this population. In this talk, the mechanisms of stimulation of MPS and suppression of MPB by protein and loading (as exercise or physical activity) in older persons will be discussed. The concept of aggressive intervention to prevent disuse-induced declines in muscle mass in older persons will also be discussed. Attendees can learn how muscle mass is regulated  and how MPS and MPB are stimulated with protein ingestion and loading.

References:
• Anker, S. D., J. E. Morley and S. von Haehling (2016). "Welcome to the ICD10 code for sarcopenia." Journal of cachexia, sarcopenia and muscle 7(5): 512-514.
• Bhasin, S., T. G. Travison, T. M. Manini, S. Patel, K. M. Pencina, R. A. Fielding, J. M. Magaziner, A. B. Newman, D. P. Kiel, C. Cooper, J. M. Guralnik, J. A. Cauley, H. Arai, B. C. Clark, F. Landi, L. A. Schaap, S. L. Pereira, D. Rooks, J. Woo, L. J. Woodhouse, E. Binder, T. Brown, M. Shardell, Q. L. Xue, R. B. DAgostino, Sr., D. Orwig, G. Gorsicki, R. Correa-De-Araujo and P. M. Cawthon (2020). "Sarcopenia Definition: The Position Statements of the Sarcopenia Definition and Outcomes Consortium." J Am Geriatr Soc 68(7): 1410-1418.
• Boirie, Y., M. Dangin, P. Gachon, M. P. Vasson, J. L. Maubois and B. Beaufrere (1997). "Slow and fast dietary proteins differently modulate postprandial protein accretion." Proc.Natl.Acad.Sci.U.S.A 94(26): 14930-14935.
• Cao, L. and J. E. Morley (2016). "Sarcopenia is recognized as an independent condition by an international classification of disease, tenth revision, clinical modification (ICD-10-CM) code." Journal of the American Medical Directors Association 17(8): 675-677.
• Oikawa, S. Y., T. M. Holloway and S. M. Phillips (2019). "The Impact of Step Reduction on Muscle Health in Aging: Protein and Exercise as Countermeasures." Front Nutr 6: 75.
• Pennings, B., Y. Boirie, J. M. Senden, A. P. Gijsen, H. Kuipers and L. J. van Loon (2011). "Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men." Am.J Clin.Nutr. 93(5): 997-1005.
• Phillips, S. M. (2017). "Current Concepts and Unresolved Questions in Dietary Protein Requirements and Supplements in Adults." Front Nutr 4: 13.
• Phillips, S. M. and W. Martinson (2019). "Nutrient-rich, high-quality, protein-containing dairy foods in combination with exercise in aging persons to mitigate sarcopenia." Nutr Rev 77(4): 216-229.
• Rutherfurd, S. M., A. C. Fanning, B. J. Miller and P. J. Moughan (2015). "Protein digestibility-corrected amino acid scores and digestible indispensable amino acid scores differentially describe protein quality in growing male rats." J Nutr 145(2): 372-379.