Abstract
Caloric restriction increases lifespan and healthspan, and limits age-associated muscle wasting. In this study, we investigate the impact of 30% caloric restriction (CR) in a murine cancer cachexia model. Forty CD2F1 mice were allocated as C26 tumor-bearing (TB) + ad libitum food intake (dietary reference intake [DRI]), TB CR, non-TB (NTB) CR, or NTB matched intake (MI). TB groups were inoculated subcutaneously with 0.5x106 C26 cells 14 days after initiating CR. Bodyweight, food intake, and grip-strength were recorded periodically. Gastrocnemius (GCM) and tibialis anterior (TA) muscles were resected and weighed 3 weeks after tumor inoculation. mRNA expression of MuRF1, Atrogin-1, myogenin, and MyoD was determined. At tumor inoculation, the mean body weight of TB CR was 88.6% of initial body weight and remained stable until sacrifice. TB DRI showed wasting before sacrifice. TB groups experienced muscle wasting compared with NTB MI. Grip-strength change was less severe in TB CR. Expression of MuRF1, Atrogin-1, and MyoD was similar between TB DRI and both CR groups. Expression of myogenin was increased in CR groups. In conclusion, caloric restriction limits loss of muscle strength but has no impact on muscle mass despite significant loss of body weight in an experimental cancer-associated cachexia model.
Highlights
Cancer cachexia describes a syndrome of progressive weight loss due to muscle wasting with or without the loss of adipose tissue, anorexia, and abnormal metabolism in the presence of underlying cancer [1]
Mice allocated to be C26 tumor-bearing (TB) animals with ad libitum access to chow were used as dietary reference intake (DRI) for all other mice in this experiment, i.e. C26 TB mice on a 30% caloric restriction (CR) diet; non-tumor bearing (NTB) mice with matched intake to the TB-DRI group (MI); NTB mice on a 30% caloric restriction diet
Cancer-associated cachexia is a common finding in patients affected by numerous types of malignancies [38, 39]
Summary
Cancer cachexia describes a syndrome of progressive weight loss due to muscle wasting with or without the loss of adipose tissue, anorexia, and abnormal metabolism in the presence of underlying cancer [1]. It cannot be reversed by conventional nutritional support and leads to progressive functional impairment [1, 2]. Catabolic cytokines and patient-related factors such as age are key pathogenic mechanisms underlying cancer cachexia [68]. Catabolic pro-inflammatory cytokines associated with cancer cachexia include interleukin-6 (IL-6), interleukin-1 beta (IL-1B), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) [7, 9]. Treatment aimed at reducing the synthesis of pro-inflammatory cytokines or blocking their action may, contribute to improved physical performance and quality of life [1113]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call