Decreasing Lean Body Mass with Age: Challenges and Opportunities for Novel Therapies

Skeletal muscle, a principal component of body composition, along with fat and bone mass, is highly important for metabolic health since divergences from normal values are associated with several pathological conditions. Skeletal muscle mass and muscle strength exhibit a steady decline after the fourth decade of life and the rate of decline is accelerated with aging [1]. Loss of skeletal muscle mass is an independent risk factor for osteoporosis, falls and fractures, impaired function and mortality [2]. For this reason, there is a great interest to define the risk factors and the mechanisms that contribute to this. Investigators with the Kangbuk Samsung Health Study evaluated the risks of rapid decreases in lean mass in reaction to age and sex among relatively young Korean adults, participants in a health screening program [3]. The authors point out that lean mass decreases significantly with aging, even among relatively young adults. This decrease was more noticeable among women who displayed a greater risk of a rapid decrease in lean mass, compared to men. Additionally, the percentage of fat mass lost increased as the participants aged. There is a considerable number of studies regarding the loss of lean mass in the elderly and its relationship with metabolic diseases as well as mortality [4]. However, this is the first largepopulation study which examined this phenomenon in a population with a relatively wide age range and demonstrated that the same phenomenon exists even in younger adults. Kim et al. [3] attributed their findings to aging processes, sex-related genetic differences and racial differences, too. Hormonal and mitochondrial factors may play important roles, too. The human skeletal muscle demonstrates age-associated mitochondrial changes, such as age-related decline in mitochondrial DNA and mRNA capacity, mitochondrial ATP production and oxygen consumption which lead to the formation of giant, bioenergetically inefficient mitochondria that release more reactive oxygen species [5]. Consequently, this mitochondrial dysfunction gives rise to activation of skeletal muscle apoptosis which causes the skeletal muscle atrophy that occurs with aging, a condition characterized by a reduction of skeletal mass, changes in protein synthesis, replacement of muscle fibers with fat and development of fibrosis [6]. It is noteworthy that the loss of muscle mass is often concealed by an unaltered or even increasing body mass index, due to increased adiposity. The co-presence of sarcopenia and obesity is defined as a syndrome which is relatively novel and it is called sarcopenic obesity (SO) [7]. These two conditions share common pathophysiological mechanisms such as insulin resistance (IR), increased levels of proinflammatory cytokines and inflammation, oxidative stress as well as specific hormonal changes. Specifically, IR, which develops with age, seems to be very closely associated with mitochondrial dysfunction, muscle fiber atrophy, changes in muscle fiber type and the development of skeletal muscle lipid deposition [7]. Moreover, insulin plays a key-role in maintaining muscle mass through stimulation of