Abstract
Sarcopenia among the older population has been growing over the last few years. In addition, the incidence of cancers increases with age and, consequently, the development of cachexia related cancer. Therefore, the elucidation of the metabolic derangements of sarcopenia and cachexia are important to improve the survival and life quality of cancer patients. We performed the 1H-NMR based serum metabolomics in adult (A) and ageing (S) Walker 256 tumour-bearing rats in different stages of tumour evolution, namely intermediated (Wi) and advanced (Wa). Among 52 serum metabolites that were identified, 21 were significantly increased in S and 14 and 19 decreased in the Wi and Wa groups, respectively. The most impacted pathways by this metabolic alteration were related by amino acid biosynthesis and metabolism, with an upregulation in S group and downregulation in Wi and Wa groups. Taken together, our results suggest that the increase in metabolic profile in ageing rats is associated with the higher muscle protein degradation that releases several metabolites, especially amino acids into the serum. On the other hand, we hypothesise that the majority of metabolites released by muscle catabolism are used by tumours to sustain rapid cell proliferation and tumorigenesis.
Highlights
Cancer-associated cachexia is a multifactorial syndrome characterised by the depletion of skeletal muscle and fat mass and cannot be fully reversed by conventional nutritional support [1].Cachexia affects the majority of advanced cancer patients, especially those with lung, head and neck, gastro-oesophageal, and pancreatic cancers, and the main consequences are associated with progressive functional impairment, reduced physical performance, altered quality of life, poor prognosis and high mortality rates [1]
No reduction in gastrocnemius muscle tissue was found in intermediated (Wi) or advanced (Wa) tumour-bearing ageing groups when compared to S group
The Walker 256 tumour experimental model was used to induce muscle atrophy related to tumour growth, termed as cancer cachexia
Summary
Cancer-associated cachexia is a multifactorial syndrome characterised by the depletion of skeletal muscle and fat mass and cannot be fully reversed by conventional nutritional support [1].Cachexia affects the majority of advanced cancer patients, especially those with lung, head and neck, gastro-oesophageal, and pancreatic cancers, and the main consequences are associated with progressive functional impairment, reduced physical performance, altered quality of life, poor prognosis and high mortality rates [1]. The elucidation of the molecular mechanisms of sarcopenia and cachexia is important to prevent the process of skeletal muscle atrophy and, improve the survival of cancer patients [4,5]. In this context, many studies have been interested in identifying circulating markers of muscle wasting process during cancer cachexia in clinical [6,7,8,9] and preclinical [10,11,12] models. Boguszewicz and colleagues [8] described serum metabolic
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