Late-life shift in caloric intake affects longevity and metabolism

Caloric restriction delays the onset of age-related changes and extends lifespan in most species, but how late in life organisms benefit from switching to a low-calorie diet is unexplored. We transferred wild type male flies from a high- to a low-calorie diet or vice versa at different times. Late-life high to low calorie diet shift immediately reduces fly mortality rate and increases lifespan. Conversely, a low to high calorie diet shift increases mortality and hazard rates. We dissected head-, thorax-, and abdomen from flies before and 2 and 5 days after shift and determined whole genome transcriptome changes. Whole genome transcriptional analyses revealed metabolic adaptations to available nutrients. Considering that the beneficial effects of calorie restriction on physiology and lifespan are conserved across many organisms, our findings suggest that CR interventions in humans may counteract the detrimental effects of high diets even when initiated later in life.