Why do some individuals live longer than others? Even identical twins have different lifespans, as do genetically identical model organisms raised in controlled laboratory environments. What then accounts for these differences? Random accumulation of damage, sudden exogenous insults, or internal biological processes that somehow diverge? We find strong evidence for the latter.

Using the nematode C. elegans, we find that prospectively long- vs. short-lived individuals are highly divergent in terms of gene regulation. Fully half of a library of promoter::GFP gene-expression reporters can effectively predict future lifespan. Moreover, these reporters represent diverse spatial and temporal expression patterns, suggesting that the regulatory states underlying long and short life are not specific to a particular tissue or a single regulatory process. Long- vs. short-lived individuals exhibit widespread, systematic, and organism-wide differences in gene regulation, well in advance of mortality.