We are interested in the role of energy metabolism and aging in human stem cell reprogramming and differentiation. In the past year, we have successfully reprogrammed cells from young and old human donors. We have examined the metabolic profiles of young and old donor cells using ultra-high throughput approaches. Remarkably, we observed differences in the metabolism of old cells compared to young cells, specifically in protein metabolism. We observed similar metabolic differences between the cells of young and old donors in mice, suggesting a conserved phenomenon. Interestingly, there was a greater variability in the ability of cells from old donors to reprogram efficiently – some old cells reprogrammed as well or even better than young cells, but some also reprogrammed more poorly, so the range was much more variable. We are currently investigating the molecular basis for this interesting difference in variability of reprogramming as individuals get older. In the past year, we have also started to examine the role of a central ‘fuel-gauge’ in the cells, the energy-sensing protein kinase named AMPK. We have generated sophisticated tools to probe the role of AMPK in the reprogramming of human cells into induced-pluripotent stem cells and in the differentiation of these induced pluripotent stem cells in specific cell types, specifically neurons and cardiomyocytes. We have also identified novel substrates of AMPK that could be particularly important in relaying the action of this central fuel gauge for stem cell function. In the next year, we plan to investigate the interaction between age and metabolism for the function and quality of stem cells generated from donors of young and old ages.