Abstract: Methods and compositions for modulating aging genes or their targets for the treatment or prevention of senescence or symptoms thereof have been developed based on the discovery of naturally occurring inhibitory nucleic acids, in particular lin-4 miRNA, that downregulate genes involved in senescence, lifespan, or age-related disorders. Representative aging genes include, but are not limited to lin-4, lin-14, let-7, lin-28, egl-35 and lin-42. Methods for identifying modulators of aging genes and targets of aging genes are also provided. The disclosed compositions are useful as diagnostics. These can be used in assays to compare genes in normal individuals, with those who are aging well or who demonstrate early senescence, and with those who have age-related disorders such as Parkinson's and Alzheimer's. The genes can be used to study the pathways and mechanisms involved in aging and age-related disorders.