Aging in humans is the results of complex biological processes that are influenced by genetics and environmental-, dietary-, and lifestyle-related factors. During aging, the function of individual organs gradually declines at a different rate, depending upon the levels of stressors. Increased oxidative stress and chronic inflammation contribute to the age-related decline in organ function and chronic diseases. Therefore, reducing these biochemical defects would be useful in maintaining healthy aging. The use of single antioxidants has produced in consistent results in human age-related chronic diseases. We have proposed that in order to simultaneously reduce oxidative stress and chronic inflammation, it is necessary to elevate the levels of cytoprotective enzymes including antioxidant enzymes and phase-2-detoxyfying enzyme through activation of the Nrf2/ARE pathway as well as dietary and endogenous antioxidants. Activation of Nrf2 becomes resistant during chronic oxidative stress; however, certain antioxidants and phytochemicals activate Nrf2 without ROS. This chapter proposes a mixture of micronutrients that would achieve the above goal, and recommends changes in diet and lifestyle for healthy aging and for reduction in age-related functional deficits. Preclinical and clinical studies to test the efficacy of proposed micronutrient mixture together with modifications in diet and lifestyle is proposed.