Ganoderma lucidum:polysaccharide ameliorates cancer cachexia with enhanced efficacy in aged group by reprogramming arginine metabolism to modulate Treg formation

Cancer cachexia is a syndrome characterized by profound weight loss, muscle wasting, and metabolic disturbance in cancer patients. Cancer-associated cachexia represents significant biological and clinical challenges that profoundly affect human health. Approximately 20 % of cancer patients succumb directly to cachexia-related complications. Aging is characterized by a gradual decline in physiological functions and an increased vulnerability to chronic diseases. However, whether aging inherently increases vulnerability to cachexia or exacerbates its progression remains unclear, impeding the development of targeted strategies for this high-risk population. Ganoderma lucidum polysaccharides (GLP) have demonstrated diverse pharmacological activities; however, their potential role in attenuating of tumor cachexia remains inadequately explored and warrants further investigation. In this study, GLP was found to mitigate tumor cachexia in vitro and in vivo models, as evidenced by rescuing significant weight loss, muscle atrophy, and adipose tissue breakdown. Notably, its therapeutic potency is more profoundly marked in aged mice than in young ones. Mechanistically, GLP alleviated myofiber atrophy and dyslipolysis by inactivating NF-κB and AMPK pathways, while also activating Treg cells by regulating arginine metabolism. In conclusion, our findings indicate that GLP exhibits cachexia-attenuating activities, thereby positioning it as a potential therapeutic candidate for aging-related conditions.