Exploring the Impact of Obesity on Skeletal Muscle Function in Older Age

Abstract

Sarcopenia is of important clinical relevance for loss of independence in older adults. The prevalence of obesity in combination with sarcopenia ("sarcopenic-obesity") is increasing at a rapid rate. However, whilst the development of sarcopenia is understood to be multi-factorial and harmful to health, the role of obesity from a protective and damaging perspective on skeletal muscle in aging, is poorly understood. Specifically, the presence of obesity in older age may be accompanied by a greater volume of skeletal muscle mass in weight-bearing muscles compared with lean older individuals, despite impaired physical function and resistance to anabolic stimuli. Collectively, these findings support a potential paradox in which obesity may protect skeletal muscle mass in older age. One explanation for these paradoxical findings may be that the anabolic response to weight-bearing activity could be greater in obese vs. lean older individuals due to a larger mechanical stimulus, compensating for the heightened muscle anabolic resistance. However, it is likely that there is a complex interplay between muscle, adipose, and external influences in the aging process that are ultimately harmful to health in the long-term. This narrative briefly explores some of the potential mechanisms regulating changes in skeletal muscle mass and function in aging combined with obesity and the interplay with sarcopenia, with a particular focus on muscle morphology and the regulation of muscle proteostasis. In addition, whilst highly complex, we attempt to provide an updated summary for the role of obesity from a protective and damaging perspective on muscle mass and function in older age. We conclude with a brief discussion on treatment of sarcopenia and obesity and a summary of future directions for this research field.

Keywords: anabolic resistance; intramuscular lipids; metabolic syndrome; muscle function; obesity paradox; sarcopenia; sarcopenic-obesity.

Figure 1

Cross-sectional MRI of the midpoint of quadriceps muscle from a young healthy individual (A) and pre-sarcopenic older individual (B) with a similar thigh circumference (~60–65 cm) and BMI (~26 kg·m²). The young-healthy individual exhibits a larger quantity of skeletal muscle mass (A) whereas high infiltration by adipose tissue is observed in the pre-sarcopenic older individual (B). (C–E) Provides an illustration of representative fiber cross-sectional images stained for Myosin Heavy Chain I (red) and lipid droplets (bodipy, green) in young lean (YL), old lean (OL), and older obese (OO), respectively. Notably, type I fiber lipid droplet number is significantly greater in young lean (n = 616) compared with older lean (n = 412) and older obese (n = 533) and greater in olden obese compared with older lean (C–E, respectively) indicative of an ‘athlete paradox', whereby young, healthy individuals exhibit higher levels of intramuscular lipids but with the superior capacity for oxidation. In addition, type II fiber lipid droplet number and area is significantly greater in the young lean (n = 377) and old obese (n = 415) compared with old lean (n = 242) individuals, despite poor whole-body metabolic health in the former (i.e., old obese), indicative of poorer muscle quality and impaired oxidative function. Further, in this study, type I and II muscle fiber cross-sectional area was greater in young lean (4,031 ± 1,978 μm², 4,009 ± 1,733 μm², respectively) compared with older obese (3,421 ± 1,528 μm², 3,390 ± 1,199 μm², respectively) and older lean (3,009 ± 1,251 μm², 2,170 ± 1,243 μm², respectively) groups and significantly greater in old obese compared with older lean [from Smeuninx et al. (85)]. White bars for (C–E) represent 50 μm.

Figure 2

Hypothetical relationship between muscle quality and the rate of muscle accretion or loss with advancing age. The dotted line represents the “muscle quality threshold” beyond which obesity-induced muscle anabolic resistance results in a precipitous, rapid decline in muscle mass and function. The arrows represent some of the factors that might influence muscle quality. The red line represents a decrease in muscle quality, whereas the green line is representative of muscle quality maintenance and the yellow line depicts the “normal” chronological aging process.

Figure 3

Proposed impacts of obesity on muscle protein turnover (MPT), in a fed state (post-prandial) and following a load-bearing activity (assuming sufficient protein intake). We speculate that, as lean mass is often preserved in obese vs. lean individuals and as obese individuals are subjected to greater loading forces and increased contractile work during activity due to the required to move more inert mass, this might elicit a positive training effect, driving muscle protein synthesis (MPS) following periods of movement, compensating for diminished MPS in response to protein provision. However, whilst little is known of the impact of obesity on MPB, there is evidence to suggest that MPB may be elevated due to a higher inflammatory burden associated with obesity.