Natural variation in rate of aging or longevity in mice and humans shows a very complex inheritance pattern. Few targeted genetic screens have identified longevity genes in mammals, partly as a result from the fact that the genetics of longevity can only be studied reliably in cohorts of mice. In this paper we propose that a combined genetic and genomic analysis of large families of fully genotyped recombinant inbred mice may provide a crucial tool to the aging research community. As a proof of principle we describe preliminary studies in which variation in gene expression patterns in hematopoietic stem cells and brain were genetically linked to longevity.