This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Mechanical stress (e.g., exercise) triggers an increase in substances known as prostaglandins (PGs) in skeletal muscle and bone. PGs are activated by the enzyme cyclooxygenase (COX). Animal studies show that an increase in PGs is essential for bone formation. When COX activity is inhibited by non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (IBUP), the bone formation response is almost completely eliminated. Acetaminophen (ACET) is an analgesic that may also inhibit COX activity in some tissues. If this occurs in human muscle and bone, it is possible that mechanical signaling in these tissues would be impaired by ACET use. The only study to address this found that both IBUP and ACET blunted the increase in PGs after one bout of resistance exercise in human skeletal muscle, and this was accompanied by a blunted increase in muscle protein build-up. It is not known whether the observed effects of ACET and IBUP on muscle PGs and protein in response to one bout of exercise persist with repeated bouts of exercise (i.e., exercise training), or whether ACET and IBUP act through similar cellular mechanisms. It is also unknown whether ACET impairs the bone building responses to mechanical loading. Accordingly, the primary aims of the proposed studies are to determine the effects of ACET on the muscle and bone adaptations to exercise training and to evaluate potential mechanisms by which ACET influence muscle metabolism; an IBUP arm will be included to gain insight into whether ACET and IBUP act through similar mechanisms. Men (n=31), aged 60 yr+, will undergo 4 months of supervised exercise training that will include high-intensity weight lifting and weight-bearing exercises to stimulate muscle and bone building. Participants will be randomized to ACET (1000 mg/d; n=12), IBUP (400 mg/d; n=7), or PLAC (n=12). We hypothesize that increases in muscle mass and bone formation markers (found in blood) will be reduced by the use of ACET compared with PLAC. We further hypothesize that molecules that signal muscle building will respond in different directions to exercise + PLAC when compared with exercise + ACET or + IBUP. The importance of this study centers on the widespread use of analgesics among the elderly, a population at increased risk for loss of muscle and bone mass, and physical impairment. Although high-intensity exercise has the potential to improve muscle mass, strength, physical function, and bone mineral density in the elderly, it is possible that the use of ACET impairs these adaptations by interfering with molecular signals in muscle and bone cells.
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