TY - JOUR TI - Global, cell non-autonomous gene regulation drives individual lifespan among isogenic C. elegans AU - Kinser, Holly E AU - Mosley, Matthew C AU - Plutzer, Isaac B AU - Pincus, Zachary A2 - Gruber, Jan A2 - Tyler, Jessica K VL - 10 PY - 2021 DA - 2021/02/01 SP - e65026 C1 - eLife 2021;10:e65026 DO - 10.7554/eLife.65026 UR - https://doi.org/10.7554/eLife.65026 AB - Across species, lifespan is highly variable among individuals within a population. Even genetically identical Caenorhabditis elegans reared in homogeneous environments are as variable in lifespan as outbred human populations. We hypothesized that persistent inter-individual differences in expression of key regulatory genes drives this lifespan variability. As a test, we examined the relationship between future lifespan and the expression of 22 microRNA promoter::GFP constructs. Surprisingly, expression of nearly half of these reporters, well before death, could effectively predict lifespan. This indicates that prospectively long- vs. short-lived individuals have highly divergent patterns of transgene expression and transcriptional regulation. The gene-regulatory processes reported on by two of the most lifespan-predictive transgenes do not require DAF-16, the FOXO transcription factor that is a principal effector of insulin/insulin-like growth factor (IGF-1) signaling. Last, we demonstrate a hierarchy of redundancy in lifespan-predictive ability among three transgenes expressed in distinct tissues, suggesting that they collectively report on an organism-wide, cell non-autonomous process that acts to set each individual’s lifespan. KW - lifespan KW - aging biomarker KW - individual variability JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -