The findings of Folick et al. are exciting because they are the first to establish a lysosome-to-nucleus signal that functions in aging regulation and to show that dietary modulation of fatty acids such as OEA has the potential to delay aging. Because genes in this pathway are conserved, the findings also provide insights on the regulation of human nuclear receptors by lysosomal signaling. Given that OEA affects feeding behavior and body weight in mice by acting through PPARα (8), dietary OEA may also have an impact on aging in mammals. The availability of bioactive lipids such as OEA could depend on the internal nutritional state of the organism. Environmental interventions such as fasting or overfeeding could alter the availability and composition of the lipid pool, consequently changing the binding status of nuclear receptors, altering downstream transcription programs, and affecting aging.