An experimental paradigm for the study of mechanisms of resistance to aging in long-lived organisms has been developed. The paradigm assumes, in concert with accumulating empirical data, that resistance to the aging processes at the organismal level will be reflected in resistance to various stressors at the cellular level. The advantage of this paradigm is that it requires neither the long-term monitoring of individuals nor the use of exceptionally old individuals. The research approach consists of: (1) verifying that primary cell cultures from the long-lived organism exhibit better resistance to key stressors than cells from related, short-lived organisms; (2) assessing differences in gene-expression before and after stress exposure in cultured cells from the long- and short-lived species in order to identify key genes involved in the stress-resistance response; (3) transfecting putative key genes from long-lived species into cells or cell lines of defined stress-resistance and hope to observe that the stress-resistance phenotype has thereby been transferred with the gene(s); (4) generating transgenic model animals containing the gene(s) of interest and look for extended life/health span. Copyright © 2001 Elsevier Science Inc.