Chronic intermittent fasting impairs β-cell maturation and function in adolescent mice

Intermittent fasting (IF) is a nutritional lifestyle intervention with broad metabolic benefits, but whether the impact of IF depends on the individual's age is unclear. Here, we investigated the effects of IF on systemic metabolism and pancreatic islet function in old, middle-aged, and young mice. Short-term IF improved glucose homeostasis across all age groups, without altering islet function and morphology. In contrast, while chronic IF was beneficial for adult mice, it resulted in impaired β-cell function in the young. Using scRNAseq, we delineated that the β-cell maturation and function score were reduced in young animals. In human islets, a similar pattern was observed in Type 1 (T1D) and Type 2 diabetes (T2D), suggesting that the impact of chronic IF in adolescence is linked to the development of β-cell dysfunction. Our study suggests considering the duration of IF in younger people, as it may enhance rather than reduce diabetes outcomes. Old (O), middle-aged (M), and young mice (Y) were randomly grouped into ad libitum (AL) and intermittent fasting (IF) groups and were exposed to 9-10 weeks of treatment or 4-5 weeks (short). In the IF group, the food was removed from midnight to the following day (24 hours later), we employed the intermittent fasting protocol 1:2, which consists of 24 hours of food starvation for 48 hours of free access to a chow diet (PMID: 29039412).