Fig. 2. A potential model for the connection between NAD⁺, sirtuins and autophagy.

Nutrient limitation increases the level of the essential cellular metabolite NAD⁺, which activates sirtuins by inducing autophagy within cells and tissues. In contrast, the activity of sirtuins and autophagy decreases during normal aging, as well as due to some diseases²⁶, and correlates with the known reduction in levels of tissue NAD⁺