Novel Directions In Therapy Against Age-Related Vascular Disease

__Abstract__ Genomic instability is recognized as one of the primary mechanisms that lead to organismal aging, and leads to progeria when developing in an accelerated pace due to defective genomic maintenance systems, such as nucleotide excision repair, in humans and mouse models of progeroid syndromes. The role of genomic instability related to nuclear DNA is currently under investigation with respect to its role in cardiovascular disease, in particular in relation to vascular aging. In this review we highlight the first findings in this field of research that come from experiment in nucleotide excision repair-defective mouse models and from genetic studies. Possible mechanisms that mediate the consequences of genomic instability at the local, vascular and at the systemic level, such as cell senescence, mutations, mitochondrial damage, and sirtuin 1 and IGF-1 decrease, are discussed and important goals for future research are set