Dr. Bruce Ames was a pioneer in understanding the role of oxidative stress and DNA damage, and in the 1990s began to make connections between micronutrient deficiencies and DNA damage. Zinc is an essential micronutrient for human health and a key component for the function of numerous cellular processes. In particular, zinc plays a critical role in cellular antioxidant defense, the maintenance of DNA integrity and is also essential for the normal development and function of the immune system. This review highlights the work helping connect zinc deficiency to oxidative stress, susceptibility to DNA damage and chronic inflammation that was initiated while working with Dr. Ames. This review outlines the body of work in this area, from cells to humans. The article also reviews the unique challenges of maintaining zinc status as we age and the interplay between zinc deficiency and age-related inflammation and immune dysfunction. Several micronutrient deficiencies, including zinc deficiency, can drastically affect the risk of many chronic diseases and underscores the importance of adequate nutrition for healthy aging.