No effects of lifelong creatine supplementation on sarcopenia in senescence-accelerated mice (SAMP8)

Abstract

-Oral creatine supplementation can acutely ameliorate skeletal muscle function in older humans, but its value in the prevention of sarcopenia remains unknown. We evaluated the effects of lifelong creatine supplementation on muscle mass and morphology, contractility, and metabolic properties in a mouse model of muscle senescence. Male senescence-accelerated mice (SAMP8) were fed control or creatine-supplemented (2% of food intake) diet from the age of 10 to 60 wk. Soleus and extensor digitorum longus muscles were tested for in vitro contractile properties, creatine content, and morphology at weeks 25 and 60. Both muscle types showed reduced phosphocreatine content at week 60 that could not be prevented by creatine. Accordingly, age-associated decline in muscle mass and contractility was not influenced by treatment. Aged soleus muscles had fewer and smaller fast-twitch glycolytic fibers irrespective of treatment received. It is concluded that lifelong creatine supplementation is no effective strategy to prevent sarcopenia in senescence-accelerated mice. muscle fiber; atrophy; contractile properties THE MARKED DECLINE in skeletal muscle mass and strength accompanying advancing age (sarcopenia) is an important public health burden. Presently, research aims to develop effective strategies to prevent age-related muscle atrophy. Hormone replacement therapy and exercise prescription have proven effective but face important limitations (7). Oral creatine supplementation can improve muscle adaptations during training (25) and promote muscle rehabilitation after leg immobilization (11), yet its long-term effectiveness in preventing sarcopenia is unknown. Short-lived additive effects of oral creatine supplementation and resistance training have been reported in older men (1, 5). However, a recent study from our laboratory failed to report beneficial effects of creatine supplementation (5 g/day) combined with exercise training over a 6-mo period in 55-to 75-yr-old men (4). In this respect, two experimental issues are of importance. First, it has recently been shown that, in healthy persons, after an initial rise during the first weeks of creatine supplementation (9, 12), muscle creatine content (and supposedly with it the related ergogenic or therapeutic effects) gradually returns to baseline levels during prolonged creatine supplementation (2). Possibly, longterm beneficial effects of creatine supplementation are only to be expected in pathological conditions that are characterized by a primary deficit in creatine metabolism leading to chronically decreased tissue creatine content such as in inborn errors of creatine synthesis and in gyrate atrophy (13,20,21). Second, despite the fact that a 6-mo to 1-yr intervention appears long according to experimental standards, such period represents only a minor fraction of the time window over which sarcopenia develops in older individuals. The current study aims to overcome the above-mentioned experimental drawbacks by investigating the effects of creatine supplementation during nea...

Tooth Loss Early in Life Accelerates Age-Related Bone Deterioration in Mice

“…SAMP8 mice show an accelerated senescence and ageassociated pathologies such as deficits in learning and memory, brain atrophy (Takeda et al 1994). SAMP8 mice were also used to mimic senile osteoporosis (Derave et al 2005;Lo et al 2009;Wauquier et al 2012;Furuzawa et al 2014). In this light, SAMP8 mice correctly mimic aging features and pathophysiologic environment regarding senile osteoporotic establishment in humans.…”

The effects of age on skeletal muscle and the phosphocreatine energy system: can creatine supplementation help older adults

“…Perhaps the most practical application of creatine supplementation in older adults is the potential to increase the quality and quantity of life[51,52]. Recently, two rodent models were used to examine the effects of long-term creatine supplementation on sarcopenia, overall health markers and survival.…”

“…Recently, two rodent models were used to examine the effects of long-term creatine supplementation on sarcopenia, overall health markers and survival. In 2005, Derave et al[51] compared the muscle mass, morphology, contractility and metabolic properties of senescence-accelerated mice (SAMP8) who were creatine supplemented (2% of food intake) from weeks 10 to 60 of life (the equivalent of supplementation in humans from the ages of 6 yr to 30-40 yr of life[53]) against a control group. Creatine supplementation was found to have no significant effect on intramuscular ATP, total creatine, phosphocreatine, or absolute muscle mass of the soleus, extensor digitalis longus and tibialis anterior muscles.…”

“…Results from Derave et al[51] and Bender et al[52] suggest that although long-term creatine supplementation may not significantly affect muscle morphology and intramuscular high-energy phosphate concentrations[51], creatine supplementation does appear to promote improved quality and quantity of life in mice, particularly when creatine supplementation began later in life and was continued until death[52]. Possible explanations to account for the results from Derave et al[51] may be a down-regulation of creatine transporter protein concentration with prolonged exposure to supra-physiological exogenous creatine concentrations resulting from creatine supplementation.…”

“…Possible explanations to account for the results from Derave et al[51] may be a down-regulation of creatine transporter protein concentration with prolonged exposure to supra-physiological exogenous creatine concentrations resulting from creatine supplementation. If correct, these results demonstrate the potential importance of cycling between periods of creatine use and disuse when consumed over long durations of time.…”