Abstract
A growing body of evidence demonstrates that the accumulation of senescent cells is a plausible ageing mechanism. It has been proposed that the senescence of vascular cells plays a causal role in the development of cardiovascular pathologies. A key prediction arising from this hypothesis is that cultures of cells derived from donors with cardiovascular disease will show reduced in vitro replicative capacities compared to those derived from disease-free controls. Accordingly, we carried out a formal review of the relationship among donor age, cardiovascular health status and maximum population doubling level attained in vitro by cultures of vascular smooth muscle and endothelial cells. Data were available to us on a total of 202 independent cell cultures. An inverse relationship was found to exist between replicative capacity and donor age in both endothelial and vascular smooth muscle cells. Cultures derived from donors with cardiovascular disease showed a lower overall replicative potential than age-matched healthy controls. In general the replicative potential at the start of the lifespan was found to be higher in those individuals without disease than those with disease and the difference in average cumulative population doublings (CPDs) in age-matched individuals in the two groups remained roughly constant throughout the lifetime. These results are consistent with the model in which the inherited replicative capacity of vascular cells is a stronger determinant of the onset of cardiovascular disease later in life, than wear-and-tear throughout the life course.
Highlights
The purpose of this article A detailed understanding of the mechanisms underlying cardiovascular disease has important implications for the reduction of mortality and morbidity in the aged population
We reviewed the available data on proliferative capacity, donor age and cardiovascular disease status with regard to these cell types, in order to produce a meta-dataset spanning a range of age groups and cardiovascular disease states, allowing provisional conclusions to be drawn
It is evident from the graphs that in the 50+ age group there are a larger proportion of points with low cumulative population doubling (CPD) values, that is, below 10 CPD in vascular smooth muscle cell (VSMC) and below 20 CPD in Endothelial cell (EC)
Summary
The purpose of this article A detailed understanding of the mechanisms underlying cardiovascular disease has important implications for the reduction of mortality and morbidity in the aged population. The majority of studies of replicative senescence have focused on human fibroblasts, as it was in these cell types that the phenomenon of cellular senescence was first reported. This has produced a distortion of the evidence base, which renders a detailed understanding on the relationship replicative senescence and health status problematic. This is because very few age-associated pathologies are directly attributable to the dermal layer. We reviewed the available data on proliferative capacity, donor age and cardiovascular disease status with regard to these cell types, in order to produce a meta-dataset spanning a range of age groups and cardiovascular disease states, allowing provisional conclusions to be drawn
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