Sexual dimorphism in the response to dietary restriction in mice: A systematic review of the literature

Background: Dietary restriction (DR) is a widely used experimental intervention in aging research due to its consistent ability to extend lifespan in most species tested. DR is an all-encompassing term describing interventions that restrict some aspect of nutrition - from calorie amount to calorie type to timing of food intake - and yet share common functional endpoints including extended longevity, but also improvements in healthspan, or the time spent in good health, as well as metabolic fitness and stress resistance. Recent studies highlight the preponderance of sexual dimorphisms in the response to DR and argue for the importance of inclusion of both sexes in preclinical research. OBJECTIVE: We set out to perform a comprehensive assessment of documented health and lifespan outcomes of interventional DR studies in mice that display sexual dimorphism. METHODS: A systematic literature search was conducted according to the PRISMA statement to identify mouse DR studies in which both sexes were included using PubMed. The specific DR interventions examined included calorie restriction (CR), intermittent fasting (IF), protein restriction (PR) and methionine restriction (MetR), with experimental endpoints focused on lifespan and healthspan. RESULTS: Sexual dimorphism in the lifespan and healthspan effects of various DR regimens is a common finding in mice, with the magnitude and direction of dimorphic responses influenced by the specific dietary intervention as well as the strain of mouse used in the study. CONCLUSIONS: Despite the fact that preclinical lifespan and healthspan analyses in mice reveal sexual dimorphism in the response to DR, there is still a large gap in our understanding of how sex affects dietary outcomes. More preclinical research comparing both sexes in the same study with better attention to reporting metrics during peer review and in easily searchable text including title and abstract is required to further our understanding of the impact of sex on health and lifespan in response to DR in rodent studies.