Sarcopenia research and practice

Sarcopenia – the loss of skeletal muscle mass and function that accompanies ageing – is now an established pathophysiological entity. There is increasing appreciation of its importance, and a growing, although incomplete, understanding of its causes. It is closely linked to physical frailty, and we are now at a point where detection of sarcopenia is beginning to be incorporated into clinical practice, and where potential interventions are beginning to undergo large clinical trials.

The on-line Age and Ageing collection of sarcopenia papers is therefore timely. We have selected key references that showcase how Age and Ageing has been involved in the development of the field, how definitions of sarcopenia have evolved, evidence on the prevalence, causes, and adverse effects of sarcopenia, as well as reviews of current therapy and insights into how the field might evolve in future. We hope that the collection will give readers not only an overview of the current state of the art, but a sense of how far we have travelled in sarcopenia research over the last few decades.

Beginnings and progress

Long before the concept of sarcopenia had acquired its current label, Maclennan and colleagues described the reduction in grip strength with increasing age, and noted only a marginal decrease in muscle mass. These two components of sarcopenia continue to be the focus of debate within the field - which is most important, which should be the target for interventions to improve, and do we really need to measure both in clinical practice?

Further work over the next few years cemented the important relationships between muscle function and clinical outcomes. Hyatt and colleagues showed that muscle strength was independently associated with activities of daily living and the need for care. Studies such as this provided the intellectual underpinning that led to increased interest in muscle function from the academic geriatric medicine community over the last twenty five years.

The paper that perhaps did more than any other to put sarcopenia on the map as a clinical entity, not just for researchers but for practitioners, was the 2010 European Working Group consensus statement. This paper provided easily accessible information on what sarcopenia is, diagnostic criteria, and diagnostic methods. It rapidly became the most highly-cited paper in history (1500 and counting!), and remains a cornerstone reference within the field. The huge number of downloads (over 60,000 at the time of writing) for this paper is testament to both its importance to researchers and its relevance to clinicians.

Definitions and prevalence

Sarcopenia prevalence is closely related to the choice of definition, and increases with age; in the BELFRAIL study by Legrand and colleagues, 12.5% of those age 80 and over were sarcopenic by the European Working Group definition. Even in the young old, such as participants in the Hertfordshire Cohort Study reported by Patel and colleagues, sarcopenia was not uncommon, affecting between 4.6 and 7.9% depending on gender and definition. Sarcopenia is a global problem, but different definitions may be appropriate for different populations. Dodds recent meta-analysis suggests that cut-offs for defining sarcopenia in developing country populations may need to be substantially different from those in western nations.

Causes and consequences

The pathophysiology of sarcopenia is complex, and not yet fully elucidated. Cesari and colleagues showed only a weak association between sarcopenia measures and endurance exercise capacity in patients with COPD, reminding us that sarcopenia is but one type of skeletal muscle dysfunction seen in older people. Diseases such as COPD and heart failure bring their own skeletal myopathies, and there may well be subtypes within the umbrella definition of sarcopenia yet to discover as well. There is plenty to find out still about the antecedents of sarcopenia. Cohorts with long follow-up periods are now giving us insight into the natural history of sarcopenia, as shown by 20 years of longitudinal data from Sweden reported by Sternang and colleagues.

Sarcopenia is linked to a number of adverse health outcomes. We now know that it is not only associated with falls, impaired activities of daily living, and the need for institutional care; sarcopenia is also associated with an earlier death. Data from the ilSIRENTE study found that sarcopenia was associated with more than double the hazard ratio for death after adjustment for confounders. Kerr and colleagues examined the relationship between grip strength and likelihood of discharge home in patients already in hospital; every 1Kg decrease in grip strength was associated with a 3% decrease in the chance of being discharged home. As the authors point out, such data make it surprising that grip strength has not yet been taken up into clinical practice more widely.

Measuring muscle function in multiple areas of the body might help with our ability to predict outcomes including mortality and hospitalisation; the Toledo cohort found that patterns of muscle weakness associated with these outcomes were different in men and women, and that weakness in multiple areas of the body improved prediction. Not every adverse event in old age is attributable to sarcopenia however; data from the EPIDOS cohortfound no association between cognitive impairment and sarcopenia.

Interventions

To date, there have been relatively few randomised controlled trials to treat sarcopenia, although this is starting to change. In a 2004 systematic review, Borst reviewed the evidence around resistance training, testosterone and growth hormone. Even at this relatively early stage in our understanding, resistance training had clear evidence of a beneficial effect in sarcopenia. An updated review from the International Sarcopenia Initiative in 2014confirmed the benefits of resistance training, but also suggested that essential amino acids (particularly leucine) might also have beneficial effects. Larger trials will confirm or refute this finding over the next few years.

Where to next?

There remains much to be done, but the future almost certainly lies in embedding sarcopenia diagnosis into clinical practice, in a better understanding of the pathophysiology of the condition, and in testing and implementing interventions to prevent or treat sarcopenia. Ensuring patient-centred outcome measures are used in trials is a key concern; it is not sufficient merely to show an improvement in muscle strength or mass, and the derivation of a disease-specific quality of life measure (SarQoL) is a recent example of a tool that may help with this. The state of the art and future direction of the field is captured well in a recent New Horizons article by Sayer and colleagues

Conclusions

The papers in the collection are chosen to both illustrate the evolution of concepts and knowledge in the field of sarcopenia, but also to showcase the breadth of current research, and to highlight the current state of the field. We are at an important juncture in the sarcopenia story, where research findings begin to cross over to influence clinical practice. The articles selected showcase the contribution made by Age and Ageingto this field, and we anticipate that the journal will continue to be a leading forum for disseminating knowledge in sarcopenia research and practice in the coming years. Witham, Miles D. University of Dundee. Aihie Sayer, Avan. University of Newcastle.

Papers:

Beginnings and progress

Is weakness in old age due to muscle wasting?
By Maclennan WJ, Hall MRP, Timothy JI, and Robinson M.
Age Ageing. 9(3): 188-192. 1980.
An early paper showing the decline in grip strength and (to a lesser extent) fat-free mass with age

Association of Muscle Strength with Functional Status of Elderly People
By Hyatt RH, Whitelaw MN, Bhat A, Scott S, and Maxwell JD.
Age Ageing. 19(5): 330-336. 1990.
This observational study showed that impaired muscle function was independently associated with impairment of activities of daily living and the need for care.

Sarcopenia: European consensus on definition and diagnosis. Report of the European Working Group on Sarcopenia in Older People
By Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel J-P, Rolland Y, Schneider SM, Topinková E, Vandewoude M, Zamboni M.
Age Ageing. 39(4): 412-423. 2010.
Landmark consensus statement on how to defined and diagnose sarcopenia, using measures such as CT, DEXA or bioimpedance for muscle mass, and functional measures such as grip strength or gait speed

Definitions and prevalence

The prevalence of sarcopenia in very old individuals according to the European consensus definition: insights from the BELFRAIL study
By Legrand D, Vaes B, Matheï C, Swine C, and Degryse, J-M.
Age Ageing. 42(6): 727-734. 2013.
Observational data showing the prevalence of sarcopenia and how low muscle mass is less common than low muscle strength and impaired function

Prevalence of sarcopenia in community-dwelling older people in the UK using the European Working Group on Sarcopenia in Older People (EWGSOP) definition: findings from the Hertfordshire Cohort Study (HCS)
By Patel HP, Syddall HE, Jameson K, Robinson S, Denison H, Roberts HC, Edwards M, Dennison E, Cooper C, and Aihie Sayer A
Age Ageing. 42(3): 378-384. 2013.
Observational data from the Hertfordshire Cohort Study showing how prevalence of sarcopenia varies depending on sex and definition.

Global variation in grip strength: a systematic review and meta-analysis of normative data
By Dodds RM, Syddall HE, Cooper R, Kuh D, Cooper C, and Aihie Sayer A.
Age Ageing. 45(2): 209-216. 2016.
A large systematic review of population-level data, showing that cutpoints for sarcopenia may need to vary across non-Western populations.

Causes and consequences

Physical performance, sarcopenia and respiratory function in older patients with chronic obstructive pulmonary disease
By Cesari M, Pedone C, Chiurco D, Cortese L, Conte ME, Scarlata S, and Incalzi RA.
Age Ageing. 41(2): 237-241. 2012.
Cross-sectional study showing only a weak association between endurance exercise capacity and sarcopenia measures in patients with COPD

Factors associated with grip strength decline in older adults
By Sternäng O, Reynolds CA, Finkel D, Ernsth-Bravell M, Pedersen NL, and Dahl Aslan AK.
Age Ageing. 44(2): 269-274. 2015.
Longitudinal study with 20 year follow up showing both differences in the trajectory of decline in grip strength between men and women, but also differences in the factors affecting the rate of decline in the sexes.

Sarcopenia and mortality risk in frail older persons aged 80 years and older: results from ilSIRENTE study
By Landi F, Cruz-Jentoft AJ, Liperoti R, Russo A, Giovannini S, Tosato M, Capoluongo E, Bernabei R, and Onder G.
Age Ageing. 42(2): 203-209. 2013.
Observational study showing that sarcopenia was associated with over twice the all-cause mortality rate in older community dwelling people.

Does admission grip strength predict length of stay in hospitalised older patients?
By Kerr A, Syddall HE, Cooper C, Turner GF, Briggs RS,and Aihie Sayer A.
Age Ageing. 35(1): 82-84. 2006.
Observational study of hospitalised older people showing that higher grip strength predicted a higher likelihood of discharge.

Association of regional muscle strength with mortality and hospitalisation in older people
By Guadalupe-Grau A, Carnicero JA, Gómez-Cabello A, Avila GG, Humanes S, Alegre LM, Castro M, Rodríguez-Mañas L, and García-García FJ.
Age Ageing. 44(5): 790-795. 2015.
Observational study showing that measurement of muscle strength in multiple body areas can improve ability to predict outcomes

Sarcopenia and cognitive impairment in elderly women: results from the EPIDOS cohort
By Abellan van Kan G, Cesari M, Gillette-Guyonnet S, Dupuy C, Nourhashémi F, Schott A-M, Beauchet O, Annweiler C, Vellas B, and Rolland Y.
Age Ageing. 42(2): 196-202. 2013.
Large observational study showing no association between sarcopenia and cognitive impairment in community-dwelling older women.

Interventions

Interventions for sarcopenia and muscle weakness in older people
By Borst SE.
Age Ageing. 33(6): 548-555. 2004.
Systematic review showing that resistance training is an effective intervention for treating sarcopenia

Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS)
By Cruz-Jentoft AJ, Landi F, Schneider SM, Zúñiga C, Arai H, Boirie Y, Chen L-K, Fielding RA, Martin FC, Michel J-P, Sieber C, Stout JR, Studenski SA, Vellas B, Woo J, Zamboni M, and Cederholm T.
Age Ageing. 43(6): 748-759. 2014.
Systematic review confirming the effectiveness of resistance training, but also suggesting potential benefits of amino acid supplementation for sarcopenia

Where to next?

Development of a self-administrated quality of life questionnaire for sarcopenia in elderly subjects: the SarQoL
By Beaudart C, Biver E, Reginster J, Rizzoli R, Rolland Y, Bautmans I, Petermans J, Gillain S, Buckinx F, Van Beveren J, Jacquemain M, Italiano P, Dardenne N, and Bruyere O.
Age Ageing.44(6): 960-966. 2015
First tool designed specifically to evaluate disease-specific health-related quality of life in patients with sarcopenia

New horizons in the pathogenesis, diagnosis and management of sarcopenia
By Aihie Sayer A, Robinson SM, Patel HP, Shavlakadze T, Cooper C, and Grounds MD.
Age Ageing. 42(2): 145-150. 2013
Comprehensive review of our current understanding of the pathology underlying sarcopenia, approaches to diagnosis, and pointers as to potential future interventions