Epidemiology of sarcopenia and insight into possible therapeutic targets

Abstract

Musculoskeletal ageing is a major public health concern owing to demographic shifts in the population. Sarcopenia, generally defined as the age-related loss of muscle mass and function, is associated with considerable risk of falls, loss of independence in older adults and hospitalization with poorer health outcomes. This condition is therefore associated with increased morbidity and health care costs. As with bone mass, muscle mass and strength increase during late adolescence and early adulthood, but begin to decline substantially from ∼50 years of age. Sarcopenia is characterized by many features, which include loss of muscle mass, altered muscle composition, infiltration with fat and fibrous tissue and alterations in innervation. A better understanding of these factors might help us to develop strategies that target these effects. To date, however, methodological challenges and controversies regarding how best to define the condition, in addition to uncertainty about what outcome measures to consider, have delayed research into possible therapeutic options. Most pharmacological agents investigated to date are hormonal, although new developments have seen the emergence of agents that target myostatin signalling to increase muscle mass. In this review we consider the current approaching for defining sarcopenia and discuss its epidemiology, pathogenesis, and potential therapeutic opportunities.

Fig.1

Cross-cohort centile curves for grip strength Centiles shown 10, 25th, 50th, 75th and 90th. ADNFS Allied Dunbar National Fitness Survey, ALSPAC Avon Longitudinal Study of Parents and Children, ELSA English Longitudinal Study of Ageing, HAS Hertfordshire Ageing Study, HCS Hertfordshire Cohort Study, LBC1921 and LBC1936 Lothian Birth Cohorts of 1921 and 1936, N85 Newcastle 85+ Study, NSHD Medical Research Council National Survey of Health and Development, SWS Southampton Women’s Survey, SWSmp mothers and their partners from the SWS, T-07 West of Scotland Twenty-07 Study, UKHLS Understanding Society: the UK Household Panel Study [25]

Fig.2

Grip strength mean values from included samples, by UN region. Each point represents the mean value of grip strength for each item of normative data, plotted against the mid-point of the age range it relates to. Values from the same sample are connected. Data from developing and developed regions are shown with triangles and circles, respectively. For comparison, the grey curve shows the mean values from our normative data for 12 British studies[36]

Fig.3

Age-adjusted incidence (per 100,000 person-years) of first-ever hip fracture among women and men residing in Rochester (1928-2006) or rural Olmsted County (1980-2006), Minnesota, by calendar year [41]

Fig.4

Cumulative effect of unhealthy behaviors (1991–93 to 2002–04) on physical functioning in 2007–09 before and after mutual adjustment for health behaviors, and additionally adjusted for body mass index (BMI). β represents mean difference in standardized score of physical functioning. Models are adjusted for age, sex, educational level, marital status, and height (and mutually adjusted for health behavior scores for bold square results). Estimates are for a 1-point increment in cumulative score of the unhealthy behavior under consideration assuming a linear association between the number of times a person was classified as having the unhealthy behavior in the three assessments (1991–93, 1997–99, and 2002–04) and physical functioning. ♦: Each health behavior separately; ■: Health behaviors mutually adjusted; ▲: Additionally adjusted for BMI [131]

Fig.5

Forest plot of studies assessing the association between birth weight (kg) and later muscle strength (kg), after adjustment for age and height. Studies ordered by mean age at time of strength measurement. B = both males and females; M = males only; F = females only included in study [139]