Vascular calcification is a serious and ubiquitous clinical problem in ageing and is set to become increasingly prevalent as populations age. It is an independent risk factor for cardiovascular (CV) mortality and emerging evidence suggests that calcification is directly causal in the induction of CV events. Calcification of the vessel media is particularly prevalent in aged populations leading to vascular stiffening and a progressive rise in after-load stress, myocardial workload and changes in diastolic perfusion that predispose to ischemia, heart failure and arrhythmia. Vascular calcification is orchestrated by vascular smooth muscle cells (VSMCs), which undergo maladaptive osteo/chondrocytic differentiation and this, combined with cell death and vesiculation, act to promote mineral deposition in the vessel wall. Vascular calcification is also prevalent in patients with premature ageing disorders such as Werner’s Syndrome and Hutchison-Gilford Progeria Syndrome, which are caused by defects in the nuclear lamina protein, Lamin A. In these patients the accumulation of a defective form of unprocessed lamin A acts to drive VSMC degeneration and patients die prematurely of myocardial infarct or stroke within the second decade. Importantly, aged VSMCs also acquire nuclear lamina defects characterized by the accumulation of prelamin A, the immature, unprocessed form of lamin A. Prelamin A accumulation drives DNA damage and premature senescence in VSMCs and this occurs concomitantly with induction of osteo/chondrocytic differentiation and upregulation of the bone-associated proteins Runx2 and alkaline phosphatase. siRNA knockdown or chemical inhibition of key proteins regulating DNA damage signalling, such as ATM/ATR, can block VSMC osteo/chondrocytic differentiation and mineralization. Evidence suggests that prelamin A acts to promote DNA damage by interfering with the nuclear translocation of key DNA damage response proteins to sites of double strand breaks. However the factors that link DNA damage to osteo/chondrocytic differentiation remain unclear. One possibility is that aged/senescent VSMCs activate an inflammatory cytokine storm, called the senescence associated secretory phenotype (SASP), and release procalcific factors such as BMP2 and IL6 which drive osteo/chondrocytic differentiation. However other more direct mechanisms may also be involved. Taken together emerging data has begun to highlight a key role for the nuclear lamina and DNA damage signalling in promoting VSMC ageing and calcification. These pathways should provide novel therapeutic targets for the amelioration of this detrimental age associated vascular pathology.