The anorexia-cachexia syndrome (ACS) is characterized by loss of appetite and unintentional weight loss. Important clinical outcomes are associated with ACS including increased risk of chemotherapy side effects, decreased survival, and quality of life. Because ACS is driven by complex metabolic mechanisms and a chronic pro-inflammatory response, the weight loss and muscle wasting cannot be reversed by conventional nutritional supplementation alone. However, insufficient intake of calories and protein exacerbate weight loss experienced by patients with ACS, while physical inactivity accelerate muscle wasting. In addition, uncontrolled symptoms, such as pain, mucositis, nausea, early satiety, and depression aggravate poor nutritional intake and are known as nutrition impact symptoms. Addressing these potentially reversible contributors to ACS requires an interdisciplinary team (IDT) effort including oncologists, palliative medicine, rehabilitation clinicians, dietitians, and psychologists. The composition and leadership of the team depends on institutional support and the patient population being treated (eg, advanced cancer vs peri-operative rehabilitation vs geriatric). Because patients may be burdened by frequent visits to multiple healthcare providers and a special skill set is required of the IDT to address ACS-measuring caloric and protein intake, assessing body composition, optimal symptom management, and providing psycho-social support-a specialized clinic would be ideal. As more effective anti-cachexia agents are being developed, nutritional rehabilitation programs and cachexia clinics could facilitate incorporation of novel treatments into multimodal management of ACS. The narrative review highlights the management of nutrition impact symptoms and the potential benefits and challenges of specialized nutrition rehabilitation programs and cachexia clinics.

Cancer-induced cachexia and anorexia are debilitating complications across many cancers, yet effective treatments remain limited due to a poor understanding of the underlying mechanisms. Here, we identify an uncharacterized tumor-immune-neural circuit driving these syndromes, centered on growth and differentiation factor 15 (GDF15). Using genetically engineered mouse models, we find that loss of GDF15 protects against appetite loss, muscle wasting, and fat loss in pancreatic, lung, and skin cancers. Single-cell RNA sequencing reveals macrophages as a major source of GDF15, induced by tumor-derived colony-stimulating factor 1 (CSF1). GDF15 acts via the central nervous system to enhance β-adrenergic signaling in the tumor microenvironment, thereby amplifying cachexia. The disruption of this feedforward loop with GDF15-neutralizing antibody, anti-CSF1R antibody, or Rearranged during Transfection (RET) inhibitor markedly reduces both cachexia and anorexia. These findings reveal a non-cell-autonomous mechanism linking tumor signals, macrophage-derived GDF15, and neural pathways, highlighting the tumor-immune-neural triad as a promising therapeutic target.

. Malnutrition in older adults. Malnutrition in older adults is a multifactorial condition with serious health and social consequences. Physiological changes such as reduced appetite, impaired taste and smell, and slower gastrointestinal signaling contribute to the "anorexia of aging." Physical impairments, including poor oral health, chewing and swallowing difficulties, and mobility limitations, further reduce food intake. Cognitive decline, dementia, depression, and delirium also compromise nutrition, while chronic diseases, inflammation, and polypharmacy increase nutritional needs or interfere with absorption. Social isolation, poverty, and inadequate institutional care exacerbate the problem. Prevalence varies by setting: about 3% in community dwelling elders, 22% in hospitalized patients, and up to 50% in those with cancer, heart failure, or in long term care. Malnutrition leads to frailty, falls, infections, longer hospital stays, disability, and higher costs. Diagnosis relies on validated tools such as the Mini Nutritional Assessment and the GLIM criteria, which combine phenotypic markers (weight loss, low BMI, reduced muscle mass) with etiologic factors (low intake, malabsorption, inflammation). Prevention and treatment require routine screening, individualized nutrition plans, and multidisciplinary approaches. Strategies include enriched diets, oral supplements, assistance during meals, social support, and, when necessary, enteral or parenteral nutrition. Early, personalized, and comprehensive interventions improve outcomes, reduce mortality, and enhance quality of life in older adults.

Cancer cachexia (CC) is a multifactorial syndrome characterized by progressive weight loss, anorexia, and loss of skeletal muscle and fat mass, resulting in reduced quality of life and poor prognosis. Currently, there are no approved pharmacological treatments for CC, highlighting the urgent need for developing novel experimental models.

Approximately 50-80 % of cancer patients suffer from cachexia, a metabolic syndrome involving inflammation, appetite loss, and muscle and fat wasting. Another common co-morbidity of cancer patients is cognitive impairment, and clinical evidence suggests the incidence of cachexia is linked to more severe cognitive symptoms. Given the difficulty of studying changes in cognitive function in human cancer patients, we set out to examine key aspects of cognitive performance in a mouse model of pancreatic cancer (pancreatic ductal adenocarcinoma; PDAC) cachexia, using an in-cage operant device (Feeding Experimental Device version 3; FED3) and a reversal learning task. Performance on the operant reversal task was compared to two control groups without cancer: ad libitum fed, sham injected with phosphate buffered saline (PBS), calorie restricted (CR) to 90-95 % of original body weight to control for reduced food intake and weight loss in cachexia mice. Our PDAC model recapitulated features of cachexia, including anorexia, weight loss, muscle wastage and inflammation. CR mice performed significantly better on the reversal task than both PDAC and PBS mice, achieving significantly more reversals and greater pellet retrieval. There was no difference between PBS and PDAC groups. These results suggest that the weight and appetite loss that occurs during cancer is processed by the brain differently to weight loss that occurs as a result of calorie restriction, with PDAC mice not experiencing an increase in motivational drive for food in line with their falling body weight. To mimic the malaise experienced by the PDAC group, we dosed CR mice with LiCl. Low dose (150 mM) LiCl did not affect responding, however, high dose (300 mM) LiCl significantly reduced both number of active pokes and pellet retrieval. This indicates a sickness-induced devaluation of reward, a factor that may impact poor performance of this task in the PDAC group. We additionally examined exploratory and anxiety-like behaviour in PBS and PDAC groups using a battery of maze-based tests. We saw no significant differences in performance between groups in the elevated plus maze, open field or light/dark box, suggesting no elevations in baseline anxiety-like symptoms in this cachexia model. These results occurred in the face of significantly elevated levels of the pro-cachexia factors GDF15, Activin A and Activin B, indicating that elevated levels of these TGF-β family peptides are not sufficient to produce behavioural changes in these tests. Our results provide evidence for a specific impact of sickness state on cognitive flexibility during pancreatic cancer.