Ageing causes a progressive deterioration of the structure and function of vascular cells that results in a decline of vascular functionality. Impaired functionality of vascular cells is a key factor that triggers several age-related vascular diseases. Most of our understanding of this process comes from in vitro studies. Further understanding of the mechanism underlying vascular aging in vivo are needed to get new insights into the pathobiology of age-associated vascular diseases. Here we use a combination of transcriptomics, immunostaining, and in vivo pharmacological and regeneration assays coupled with the extracorporeal vasculature of the invertebrate chordate Botryllus schlosseri (which is large, transparent, accessible and easy to manipulate) and show that we can study morphological, transcriptional and functional age-associated changes of vascular cells that are similar to those of mammalian vascular cells from tissue culture and fixed vascular cells. We showed that age-associated changes in the cytoskeleton and the ECM reshape vascular cells into flatten and elongated form and heavily accumulate Collagen, rendering the vessels into more rigid and less responsive to pharmacological insults. These changes did not alter the regeneration potential of aged blood vessels and newly regenerated vascular cells retained the same aged phenotype. Furthermore, we found that a subset of blood circulating hemocytes showed reduced proliferation while increasing apoptosis in aged animals. Overall design: mRNA profiles of 3 generations of Botryllus schlosseri colonies (each in triplicates) using illumina deep sequencing and analyzed for differential expression between the youngest and the oldest age. We used the following genotypes: SB825_g1 (3 years old), SB825_g2(F1 from SB825_g1 genotype 2 years old), SB825_g3 (F1 from SB825_g2 genotype 4 months old) SMG_g1 (3 years old), SMG_g2(F1 from SMG_g1 genotype 2 years old), SMG_g3 (F1 from SMG_g2 genotype 4 months old) SMH_g1 (3 years old), SMH_g2(F1 from SMH_g1 genotype 2 years old), SMH_g3 (F1 from SMH_g2 genotype 4 months old)