Sarcopenia and Muscle Aging

Speaker: Patrick Dehail, MD, PhD, Service de Médecine Physique et Réadaptation & EA 4136, CHU de Bordeaux, Université de Bordeaux 2; Bordeaux, France.

Dr. Patrick Dehail focused on the mechanisms and functional impact of and therapeutic approaches to sarcopenia and muscle aging.

Defining Sarcopenia
Sarcopenia is a progressive process of age-related muscle mass (MM) loss. Its prevalence is high, from 10-24% in 65-70-year-olds to over 30% in those over 80 years old.

Sarcopenia is characterized by a muscle mass index (MMI) (appendicular skeletal MM [kg]/height² [m²]) at least two standard deviations lower than the MMI in a younger population.¹ A threshold that takes into account muscle performance and describes MM loss that has a functional impact is of the greatest utility.

In older adults, MM loss is associated with increased fat mass. It is important to take these two processes into account because fat mass affects the consequences of sarcopenia.

Age-related Changes and Mechanisms Involved in Muscle Tissue
Sarcopenia is associated with muscle tissue changes such as a decrease in the number and atrophy of type II skeletal fibres, while type I fibres are more preserved (Figure 1). At the molecular level, aging is associated with a decreased expression of myosin heavy chain (MHC) IIa and IIx isoforms, while the level of expression of MHC I tends to remain constant. There is an increase in the total number of hybrid fibres coexpressing various MHC isoforms.
Mechanisms involved in muscle aging include motor unit changes, inactivity, and the dysregulation of muscle protein synthesis and apoptosis.

The aging process is associated with a 25-50% reduction of the a-motoneurons (a-MN). Small MN, which are more preserved than large a-MN, continue to innervate type I fibres. Over many years, the loss of large a-MN is compensated by a sprouting phenomenon: small MN will take over and innervate orphan type II muscle fibres, which will become type I fibres. Eventually, however, the new giant motor units constituted through the sprouting phenomenon are lost and, beyond a certain threshold, this loss will lead to a functional impact.

Inactivity is viewed as an etiologic factor of sarcopenia. However, it is not known whether inactivity is the consequence of neuromuscular changes (adaptation) or a factor contributing to these changes.

Dr. Dehail described the dysregulation of muscle protein synthesis as playing an important role in sarcopenia. Splanchnic sequestration diverts amino acids to the liver or the intestine. Secondly, insulin resistance, which is more prevalent in older adults, plays a role essentially by increasing proteolysis of muscular proteins. A decreased level of metabolic hormones (testosterone, GH-IGF1 axis, DHEA) also contributes to this dysregulation. Finally, the elevated level of proinflammatory cytokines (in particular, IL6 and TNF-a) seen in older adults stimulates proteolysis. Additionally, decreased MGF levels (a factor that stimulates the pool of satellite cells), and increased level of myostatin (a muscle growth inhibitor) and apoptosis also contribute to sarcopenia.

Aging is also associated with microcirculatory changes that affect muscle tissue.

Malnutrition, anorexia, and decreased vitamin D and vitamin D receptors (VDR) levels are common in older adults. Prevalence of vitamin D deficiency exceeds 90% in hospitalized older adults. Vitamin D affects protein synthesis and the functional capacity of muscle tissue. There is a correlation between the levels of 25-hydroxyvitamin D (25-OHD) and loss of muscular strength. Visser et al. showed that subjects with a 25-OHD level <25 nmol/l were more likely to lose their grip strength at