Aging is characterized by spontaneous biochemical changes that may predispose to increased susceptibility to diseases. Zinc may remodel these changes leading to healthy aging because zinc improves antioxidant defense via CLU protein and genomic stability via PARP-1 nuclear enzyme and repairs oxidized proteins via Msr A protein. The intracellular zinc homeostasis is regulated by metallothioneins (MT), which are unable in zinc release in aging, causing impaired antioxidant response restored by zinc supplementation. Here, the choice of old subjects for zinc supplementation is discussed in relation to their genetic background of MT and IL-6, because both affect intracellular zinc homeostasis.