Aging affects all organs. Arteries, in particular, are among the most affected. Vascular aging (VA) is defined as age-associated changes in function and structure of vessels. Classical VA phenotypes are carotid intima-media thickness (IMT), carotid plaque (CP), and arterial stiffness (STIFF). Individuals have different predisposition to these VA phenotypes and their associated risk of cardiovascular events. Some develop an early vascular aging (EVA), and others are protected and identified as having supernormal vascular aging (SUPERNOVA). The mechanisms leading to these phenotypes are not well understood. In the Northern Manhattan Study (NOMAS), we found genetic variants in the 7 Sirtuins (SIRT) and 5 Uncoupling Proteins (UCP) to be differently associated with risk to developing VA phenotypes. In this article, we review the results of genetic-epidemiology studies to better understand which of the single nucleotide polymorphisms (SNPs) in SIRT and UCP are responsible for both EVA and SUPERNOVA. Display omitted •Vascular aging (VA) is an age-associated changes in function and structure of vessels.•Individuals have different predisposition to VA phenotypes.•Some individuals develop an early vascular aging (EVA).•Some individuals are protected and identified as having supernormal vascular aging (SUPERNOVA).•Single nucleotide polymorphisms in SIRT and UCP are responsible for both EVA and SUPERNOVA.