Andres Kriete

Complementary to the theoretical work I address energetic perturbations in aging through experimentation. My group has established an aging model for post-mitotic cells through “Energy Restriction in Quiescence” (ERiQ). This cell model demonstrates metabolic stress and transcriptional deregulation seen in many aging tissues, which may underlie the development of age-related diseases involving deregulation of the Akt, mTOR, NF-kappaB and p53 signaling pathways. I have suggested that aging is a robustness tradeoff: cellular responses are tuned to provide survival to acute stressors, but these responses conflict with longevity assurance. To demonstrate, we assembled generic whole cell computational models using feedback loop motifs from control theory in conjunction with rule-based descriptors simulating the progression of aging. Such models can be executed rapidly and repeatedly to study the effect of molecular mechanisms on the aging phenotype.