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Genetic Variation in Organ System Decline Across the Drosophila Genetics Reference Panel

Preprint Created on 19 Sep 2026 bioRxiv

Genetic background has a significant impact on an organism's lifespan. Underlying this metric, ageing is characterised by a sequence of physiological systems decline that leads to death. Despite this, much of the ageing research performed on model organisms in the lab uses lifespan, rather than physiological decline, as a metric to measure ageing. Here, we sought to establish if differing genotype alters age-related organ system decline by repeatedly measuring the function of five organ systems throughout the lifespan of 19 lines from the Drosophila Genetic Reference Panel. We found that the magnitude of each organ system's decline differs across genotypes, and that different organ systems decline at different rates within a genotype. We also uncovered that while declines in activity rate and reproduction were associated with length of life, overall patterns of phenotypic organ system decline differed significantly across genotypes. Overall, these data suggest that individuals with different genetic backgrounds have distinct patterns of physiological decline, implying that the mechanisms driving ageing vary between individuals. These data underscore the importance of studying organ systems decline in addition to lifespan to gain a full understanding of ageing.

Del Tito, J. F., Alton, L. A., Piper, M. D., Mirth, C. K.

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