Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space

Abstract

The decline in muscle function is associated with an age-related decrease in muscle mass and an age-related decline in strength. However, decreased strength is not solely due to decreased muscle mass. The age-related decline in muscle-specific force (force/muscle cross-sectional area), a measure of intrinsic muscle function, also contributes to age-related strength decline, and the mechanisms by which this occurs are only partially known. Moreover, changes in the extracellular space could have a profound effect on skeletal muscle function. Life-long calorie restriction in rodents has shown to be a powerful anti-aging intervention. In this study, we examine whether calorie restriction is able to attenuate the loss of muscle function and elevations in extracellular space associated with aging. We hypothesize that calorie restriction attenuates the age-associated decline in specific force and increases in extracellular space. Measurements of in vitro contractile properties of the extensor digitorum longus (type II) and soleus (type I) muscles from 12-mo and 26- to 28-mo-old ad libitum-fed, as well as 27- to 28-mo-old life-long calorie-restricted male Fischer 344 rats, were performed. We found that calorie restriction attenuated the age-associated decline in muscle mass-to-body mass ratio (mg/g) and strength-to-body mass ratio (N/kg) in the extensor digitorum longus muscle (P < 0.05) but not in the soleus muscle (P > 0.05). Importantly, muscle-specific force (N/cm2) in the extensor digitorum longus, but not in the soleus muscle, of the old calorie-restricted rats was equal to that of the young 12-mo-old animals. Moreover, the age-associated increase in extracellular space was reduced in the fast-twitch extensor digitorum longus muscle (P < 0.05) but not in the soleus muscle with calorie restriction. We also found a significant correlation between the extracellular space and the muscle-specific force in the extensor digitorum longus (r = -0.58; P < 0.05) but not in the soleus muscle (r = -0.38; P > 0.05). Hence, this study shows a loss of muscle function with age and suggests that long-term calorie restriction is an effective intervention against the loss of muscle function with age.

Lifelong exercise and mild (8%) caloric restriction attenuate age-induced alterations in plantaris muscle morphology, oxidative stress and IGF-1 in the Fischer-344 rat

“…Previous studies have demonstrated that moderate caloric restriction (30-40%) with adequate nutrition results in significant protection against accelerated loss of muscle mass/body mass ratio and fiber cross-sectional area with advancing age in rodents (Dirks and Leeuwenburgh, 2004;McKiernan et al, 2004). Several investigators have noted that the moderate caloric restriction protected against age-induced decreases in muscle weight to body weight ratio (Payne et al, 2003;Selman et al, 2002). Payne et al (2003) showed that 40% caloric restriction resulted in greater muscle mass/body mass ratio of fast-twitch muscle (e.g., extensor digitorum longus), higher fiber cross-sectional area, and higher specific force (N/cm 2 ), when compared with old rats fed ad libitum.…”

“…Several investigators have noted that the moderate caloric restriction protected against age-induced decreases in muscle weight to body weight ratio (Payne et al, 2003;Selman et al, 2002). Payne et al (2003) showed that 40% caloric restriction resulted in greater muscle mass/body mass ratio of fast-twitch muscle (e.g., extensor digitorum longus), higher fiber cross-sectional area, and higher specific force (N/cm 2 ), when compared with old rats fed ad libitum. Phillips and Leeuwenburgh (2005) also reported that 40% caloric restriction preserved muscle mass/body mass ratio in the superficial vastus lateralis muscle (fast-twitch).…”

“…After this initial atrophy, muscle mass tends to remain fairly steady in rodents. For example, absolute soleus and EDL mass was reduced by moderate (40%) caloric restriction compared with the ad libitum (Payne et al, 2003). Since rats continue to grow longitudinally throughout their lifespan, it can be argued that muscle mass/body mass ratio is a more meaningful marker of muscle preservation and function than absolute mass, and may indicate that both 8% CR and mild exercise could be effective in reducing sarcopenia.…”

“…McKiernan et al (2004) found that lifelong 40% caloric restriction results in a significant decrease in the rate of muscle mass loss, and attenuates age-induced fiber loss. Recent research also indicates that caloric restriction prevents the age-induced decrease in muscle contractile force per cross-sectional area (Mayhew et al, 1998;Payne et al, 2003). Moreover, caloric restriction compensated for decrements in muscle mass specific VO 2max (maximal aerobic capacity) and mitochondrial oxidative capacity that occur with aging (Hepple et al, 2005).…”

“…Moreover, the amount of connective tissue also increases with aging, resulting in increased internal work, which in turn leads to increased energy requirement and thus reduced mechanical efficiency. Thus morphological changes in skeletal muscle with aging include a reduction of fiber cross-sectional area, loss of fiber number, and increases in extramyocyte space and connective tissue (Caccia et al, 1979;Chung and Ng, 2006;Grimby and Saltin, 1983;McCarter and McGee, 1987;Payne et al, 2003). The etiology of age-associated changes in muscle morphology is believed to be multifactorial, and includes reduced physical activity, increased insulin resistance, and impaired endocrine function (e.g., low testosterone, growth hormone, and thyroxine) (Evans, 2004).…”