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

Area of Science:

• Metabolic health
• Endocrinology
• Aging research

Background:

• Intermittent fasting (IF) is a popular dietary strategy with known metabolic advantages.
• The influence of IF on metabolic health across different age groups remains incompletely understood.

Purpose of the Study:

• To investigate the age-dependent effects of intermittent fasting on systemic metabolism and pancreatic beta cell function.
• To compare the impact of short-term versus chronic IF on metabolic parameters in mice of varying ages.

Main Methods:

• Utilized a mouse model across three age groups (young, middle-aged, old) to assess IF effects.
• Employed short-term and chronic IF protocols.
• Analyzed systemic metabolism and pancreatic islet function.
• Applied single-cell RNA sequencing (scRNA-seq) to characterize beta cell function at a molecular level.
• Examined human islets from individuals with type 1 (T1D) and type 2 (T2D) diabetes.

Main Results:

• Short-term IF improved glucose homeostasis in all age groups without affecting islet morphology or function.
• Chronic IF benefited adult mice but impaired beta cell function in young mice.
• scRNA-seq revealed reduced beta cell maturation and function scores in young mice subjected to chronic IF.
• A similar pattern of impaired beta cell function was observed in human islets from T1D patients, but not T2D patients.

Conclusions:

• The duration of intermittent fasting is a critical factor, with chronic IF negatively impacting beta cell function in younger individuals.
• These findings suggest that chronic IF in adolescence may be linked to the development of beta cell dysfunction and potentially worsen diabetes outcomes.
• Clinical recommendations for IF should consider age and duration to optimize metabolic health and prevent adverse effects, particularly in younger populations.