Electron transport via NADH generates NAD+ in mitochondria and may decline with age. In young mitochondria, NADH, made by the citric acid cycle, readily donates its electrons to complex I of the electron transport chain (ETC) and thereby generates NAD+. During the aging process, DNA damage accumulates in the nucleus, causing PARP activation and NAD+ reduction. Consequently, SIRT1 activity is reduced, resulting in increased PGC-1α acetylation and decreased TFAM levels. These nuclear events might reduce mitochondrial function in old mitochondria by affecting mitochondrial complex I and other mitochondrial components, or blocking the entry of electrons from NADH into the ETC, thereby creating an NAD deficiency.