Aging, telomeres, and atherosclerosis

Abstract

Although the level and pace of population aging display high geographical variability, virtually all countries have been experiencing growth in their elderly population, particularly in developed nations. Because aging is a major risk factor for atherosclerosis and associated disease, it is of up most importance to unravel the molecular mechanisms involved in vascular aging. Telomeres are specialized DNA-protein structures located at the ends of eukaryotic chromosomes whose length is progressively reduced in most somatic cells during aging. It is accepted that telomere exhaustion contributes to organismal ageing at least by impairing cell proliferation and viability. An emerging question is whether telomere erosion contributes to atherosclerosis. Here we discuss recent advances on the molecular control of telomere length in vascular cells, as well as animal and human studies that address the role of telomeres in vascular pathobiology. Although the interrelationships between telomere length and cardiovascular disease appear obvious, a chief question that remains unanswered is whether telomere ablation is cause of vascular injury or a surrogate phenomenon.

Absence of telomere shortening and oxidative DNA damage in the young adult offspring of women with pre-gestational type 1 diabetes

“…We hypothesised that this would extend into early adulthood [30], as others have shown in animal models that adverse fetal environments are associated with shortened telomere lengths and adult morbidity [40][41][42]. Telomere attrition has attracted attention in the last 2 years as a possible predeterminant of later risk of cardiovascular disease [19][20][21]. However, we found no evidence of residual telomere shortening in multiple blood cell lines or in fibroblasts, and no evidence of an increased risk of senescence in vitro in fibroblasts.…”

“…Type 1 diabetes offers a very hostile intrauterine environment, and is associated with high rates of fetal morbidity, including increased risks of congenital malformation, spontaneous abortion and perinatal death [39]. The fetal morbidity associated with maternal diabetes (and other embryopathies) reflects increased intrauterine oxidative stress and fetal oxidative DNA damage [11,12,[17][18][19][20][21][22][23][24]. The increased fetal DNA damage described in diabetes pregnancy must lead to increased telomeric DNA damage, as the GGG sequence in telomeric DNA is particularly susceptible to DNA damage [17].…”

“…The increased fetal DNA damage described in diabetes pregnancy must lead to increased telomeric DNA damage, as the GGG sequence in telomeric DNA is particularly susceptible to DNA damage [17]. It therefore follows that elevated levels of telomere attrition at cell division during fetal development should lead to offspring born programmed towards senescent angiogenic and endothelial precursors [19][20][21], with shorter telomeres than their peers born to mothers without diabetes. We hypothesised that this would extend into early adulthood [30], as others have shown in animal models that adverse fetal environments are associated with shortened telomere lengths and adult morbidity [40][41][42].…”

“…Rates of telomere shortening at cell division are highly dependent on oxidatively induced strand breaks in telomeric DNA and oxidative DNA damage [11,12,17,18]. Feto-placental telomere attrition is an attractive hypothetical bridge between the adverse intrauterine environment and preprogramming of the offspring towards senescent phenotypes [19][20][21], as an adverse intrauterine environment increases oxidative damage to feto-placental DNA and fetal vascular endothelium [22][23][24]. We have previously suggested that this mechanism could account for a senescent phenotype in the adult offspring of women with type 1 diabetes [25].…”

Telomere length may be associated with hypertension

“…1 Telomere shortening has been found in vascular endothelial cells, smooth muscle cells and cardiomyocytes during aging. 2 Thus, the purpose of this study was to compare the telomere length of hypertensive patients and control subjects from the community.…”