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Grant Abstract: PDQ6: Loss of adiponectin as a contributing factor in cancer cachexia

Grant Number: 5R21CA185140-02
PI Name: Belury
Project Title: PDQ6: Loss of adiponectin as a contributing factor in cancer cachexia

Abstract: Sarcopenia is the loss of skeletal muscle mass, strength and function that often accompanies aging. Factors that contribute to age-related sarcopenia include impaired anabolism (protein synthesis and muscle regeneration) and accelerated muscle catabolism. While the sequence of events that cause sarcopenia are not clearly delineated, accelerated muscle loss happens with obesity, insulin resistance and heightened baseline levels of inflammation. Dysregulated energy metabolism is linked with mitochondrial dysfunction that predicts for further decline of skeletal muscle mass and function. As a stimulator of mitochondrial activity, exercise is a leading therapy recommended for the prevention of sarcopenia. However, due to poor long-term compliance to exercise, efforts are underway to identify therapies that mimic many of the effects of exercise. These ‘exercise mimetics,’ activate the energy sensor, AMP-kinase (AMPK) and induce mitochondrial biogenesis propose that the dietary supplement, naringenin, is an exercise mimetic that may be useful for the prevention of sarcopenia. In this administrative supplement to grant R21CA185140, we propose to test naringenin to prevent degeneration of muscle structure and function in a murine model for age-associated sarcopenia. This Administrative Supplemental grant will test the hypothesis that dietary naringenin prevents sarcopenia in older mice through modulating mitochondrial activity. This proposal complements many aspects of the parent grant R21CA185140 which seeks to elucidate myocellular mechanisms involving mitochondria that are dysregulated in cancer cachexia.

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