As a first step towards investigating the effects of genetic variation in aging-related genes on human lifespan and health, we characterized genetic variation in healthy oldest-old. To assess the genetic variation in a selection of aging-related candidate genes we have re-sequenced 24 genes in healthy seniors 85 years old or older. Candidate genes were selected either through gene expression analysis of long-lived C. elegans daf-2 mutants [10] or literature reports. Genes previously identified as differentially expressed in long-lived daf-2 mutants compared to wild type worms included genes involved in metabolism (IGF1R (GeneID: 3480), SCD (GeneID: 6319), APOB (GeneID: 338)) and stress response (CRYAB (GeneID: 1410), HSPB2 (GeneID: 3316)). Response to dietary restriction (DR) is suggested to be an evolutionary conserved mechanism that enhances survival in adverse environmental condition but also extends lifespan [22]. Key genes of dietary restriction-mediated lifespan extension have been identified in animal studies and include sirtuins (SIRT1 (GeneID: 23411), SIRT3 (GeneID: 23410)), uncoupling proteins (UCP2 (GeneID: 7351), UCP3 (GeneID: 7352)), PPARG (GeneID: 5468) and PPARGC1A (GeneID: 10891). Additional candidate gene categories chosen, included autophagy (BECN1 (GeneID: 8678),
