Neuronal susceptibility to GRIM in Drosophila melanogaster measures the rate of genetic changes that scale to lifespan

Gene expression in Drosophila melanogaster changes significantly throughout life and some of these changes can be delayed by lowering ambient temperature and also by dietary restriction. These two interventions are known to slow the rate of aging as well as the accumulation of damage. It is unknown, however, whether gene expression changes that occur during development and early adult life make an animal more vulnerable to death. Here we develop a method capable of measuring the rate of programmed genetic changes during young adult life in D. melanogaster and show that these changes can be delayed or accelerated in a manner that is predictive of longevity. We show that temperature shifts and dietary restriction, which slow the rate of aging in D. melanogaster, extend the window of neuronal susceptibility to GRIM over-expression in a way that scales to lifespan. We propose that this susceptibility can be used to test compounds and genetic manipulations that alter the onset of senescence by changing the programmed timing of gene expression that correlates and may be causal to aging.