Vanillin inhalation ameliorates age-related appetite decline via multi-target modulation

With the accelerating trend of global population aging, age-related appetite decline has become an increasingly severe public health challenge. This study aimed to investigate the effects and underlying mechanisms of inhaling nebulized vanillin, a natural aromatic compound, on improving appetite in aging organisms. After a 30-day intervention, vanillin inhalation significantly increased short-term food intake and promoted weight gain in naturally aged mice. At the mechanistic level, the intervention activated the olfactory-hypothalamic neural pathway, up-regulated the expression of the orexigenic neuropeptide AgRP and the hormone ghrelin, while simultaneously suppressing the anorexigenic signals POMC and MC4R. Furthermore, the treatment alleviated systemic inflammatory responses, reshaped the gut microbiota structure, enriching Limosilactobacillus and Lactobacillus , and modulated tryptophan-related metabolic pathways. Multi-omics correlation analysis further revealed the integral regulatory role of the gut microbiota-metabolism-brain axis in this process. These findings provide important scientific evidence for nutrition intervention strategies based on aromatherapy to ameliorate age-related appetite decline.