Just as intriguing is a recent study that revealed that rapamycin treatment, which extends mouse lifespan, reduces the incidence of senescent cells in vivo. Our findings provide strong support for a causal relationship between Meth-R-induced stress resistance, extended replicative lifespan and improvements in rodent healthspan. Perhaps our most important finding, however, is that genetic Meth-R confers stress resistance to cultured human fibroblasts, as well as a reduced doubling time and an extension of replicative lifespan. In fact, the current study represents the first investigation into the putative effects of Meth-R on human cells for the purpose of ameliorating age-related phenotypes. Notably, our discovery of the beneficial effects of Meth-R on human cell replicative lifespan is supported by a recent study demonstrating that depletion of cystathionine beta synthase, a manipulation predicted to increase intracellular methionine levels, reduces the lifespan of cultured human endothelial cells. Given the low methionine Sodium Gluconate content of the vegan diet, dietary Meth-R is a conceivable strategy for promoting healthy aging in humans. However, it might not be practical or desirable due to potential side effects. Yet, and BIX 01294 Moreover, understanding Meth-R-responsive mechanisms promises to reveal key biochemical pathways impacting aging, which could be targeted by new strategies to ameliorate age-related diseases in an optimal fashion. While it is not currently known whether Meth-R is effective in humans, our discovery that it extends the replicative lifespan of cultured mouse and human cells strongly supports this possibility. With respect to the mechanistic basis of Meth-R, our findings suggest that the benefits conferred to human cells by this intervention are associated with activation of NFkB-mediated retrograde signaling. We anticipate that future work will ultimately identify which pathways engaged by Meth-Rdependent NFkB signaling underlie the pro-survival benefits of this intervention. Moreover, we are hopeful that Meth-Rdependent pathways might be selectively manipulated for the purpose of promoting healthy aging in humans, an effort that will be facilitated by our development of experimentally tractable Meth-R model systems.