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Cancer cachexia is the loss of lean muscle mass with or without loss of fat mass that is often highlighted by a progressive loss of skeletal muscle mass and function. The mechanisms behind the cachexia‐related loss of skeletal muscle are poorly understood, including cachexia‐related muscle functional impairments. Existing models have revealed some potential mechanisms, but appear limited to how the cancer develops and the type of tumors that form. We studied the C57BL6/J (B6) ApcMin/+ Tg::Fabp1‐Cre TG::PIK3ca* (CANCER) mouse. In this model, mice develop highly aggressive intestinal cancers. We tested whether CANCER mice develop cancer cachexia, if muscle function is altered and if sex differences are present. Both female and male mice, B6 (CONTROL) and CANCER mice, were analyzed to determine body weight, hindlimb muscle mass, protein concentration, specific force, and fatigability. Female CANCER mice had reduced body weight and hindlimb muscle mass compared with female CONTROL mice, but lacked changes in protein concentration and specific force. Male CANCER mice had reduced protein concentration and reduced specific force, but lacked altered body weight and muscle mass. There were no changes in fatigability in either group. Our study demonstrates that CANCER mice present an early stage of cachexia, have reduced specific force in male CANCER mice and develop a sex‐dependent cachexia phenotype. However, CANCER mice lack certain aspects of the syndrome seen in the human scenario and, therefore, using the CANCER mice as a preclinical model does not seem sufficient in order to maximize the translation of preclinical findings to humans., The mechanisms behind the progressive loss of skeletal muscle mass and function seen in patients with cancer cachexia are still largely unknown, thus we tested whether a new murine model of colorectal cancer could better represent the human condition. We concluded that although the tumor‐bearing model tested had reductions in body weight, muscle mass, specific force and a sex‐specific phenotype, the model tested had a limited lifespan and ultimately impaired the ability to translate findings to the human condition.

Substrate utilization favors fatty acid oxidation in normal healthy hearts. Aging is associated with attenuated mitochondrial biogenesis and fatty acid metabolism in the heart, but the mechanism of...

Aging is associated with declining cardiac contractile function as well as changes in substrate metabolism and mitochondrial function. The relationship between age-related changes in cardiac metabo...

Mechanisms underlying sarcopenia in skeletal muscle have not been fully elucidated, but mitochondrial dysfunction appears to play a role. The PGC-1α mediated pathway plays an important role in prom...

Aging is associated with declining cardiac contractile function as well as changes in metabolism and mitochondrial function. The relationship between age‐related changes in cardiac metabolism and declining cardiac contractile function has not been determined. In order to define the role energetics play in changes in contractile function, we measured mitochondrial NADH, [NADH] m , during continuous contractions of isolated left ventricular myocytes from young (Y) and old (O) FBN rats. Second, we explored the role of metabolic disruption with rotenone and increased workload with isoproterenol (ISO) had on age‐related changes in myocytes shortening. Single, intact myocytes were stimulated for 10 min of continuous contraction at either 2 Hz or 4 Hz while being perfused with Ringer9s solution. Properties of shortening (peak shortening and rate of shortening) were measured at the onset (T0) and after 10 min (T10) of continuous contraction, and the decline in shortening over time (T10/T0) was determined. Although young and old myocytes had similar contractile function under resting conditions, old myocytes demonstrated decrements in [NADH] m during continuous stimulation, while young myocytes maintained constant [NADH]m over this time. In addition, old myocytes exhibited impaired contractile function to a workload (ISO) and metabolic (rotenone) stress compared to young myocytes. Taken together, these results demonstrated that old myocytes are susceptible to stress‐induced contractile dysfunction which may be related to altered cellular energetics.

Using an intact rat model we studied the role of alpha and beta adrenergic agonists in recruiting intrapulmonary arteriovenous anastamoses (IPAVs). Exercise and hypoxia, which recruit IPAVs, activa...

It is recognized that with ageing of the rodent heart there is a shift in myosin heavy chain (MHC) isoform from α-MHC to β-MHC. Previous studies have shown evidence of significant regional differen...