Circadian feeding promotion by Ninjin'yoeito counteracts frailty in aged mice

Frailty in aging is a major health challenge, requiring solution. Older people with frailty often exhibit malnutrition and dysregulated feeding. Feeding behavior displays circadian rhythm, while aging and frailty involve rhythm disorders, suggesting possible role of circadian feeding in frailty and treatment. Herbal medicine, Ninjin'yoeito (NYT), reportedly ameliorates frail symptoms. The present study explored impacts of NYT on circadian feeding and psychological/physical functions in aged mice. Here, we report that oral NYT independent of administration timing increases food intake specifically in 18:00-20:00, the pre-active phase, in aged and young mice, an effect mimicked by Chenpi and hesperidin. NYT altered appetite-regulating hormones and neuropeptides in pre-active phase. Repeated NYT administration restored anti-anxiety behavior, memory, and grip strength that declined in aged mice. These effects were blocked by food deprivation and pair-fed to control selectively in 18:00-20:00. These results reveal pre-active phase feeding promotion as a novel avenue to intervene aging-related frailty.