Endothelial progenitor cells from aged subjects display decreased expression of sirtuin 1, angiogenic functions, and increased senescence

Abstract

Studies have demonstrated that aging is associated with a substantial decline in numbers and angiogenic activity of endothelial progenitor cells (EPCs). In view of senescence being an important regulator of age-related cell survival and function, in the current study, we correlated EPCs numbers and functions with their senescence status and mechanisms in young and elderly subjects. Healthy young subjects (n = 30, below 60 y) and old subjects (n = 30, equal to or above 60 y) participated in the study. Subjects had no significant disease or risk factors of disease and aging was the only risk factor in the aged subjects. Enumeration of CD34-vegfr2 dual positive EPCs was performed. The ex vivo culture of EPCs was done to study colony formation, migration, and senescence-associated beta-galactosidase activity. The expression of cell cycle and senescence regulatory proteins including, p53, p21, and sirtuin 1 (SIRT1), a deacetylase protein was studied in cultured EPCs by RT-PCR and immunofluorescence staining. In vivo proliferation, ex vivo colonies, migration, and secretory ability of EPCs was significantly higher in young subjects than that in elderly subjects. EPCs in old subjects showed enhanced senescence and decreased expression of SIRT1 in comparison to that observed in young subjects. An inhibition of SIRT1 in EPCs of young subjects led to significant increase in senescence and reduction of cell differentiation. The study suggests that EPCs have decreased proliferation and functions in aged subjects due to increased senescence which may be attributable to decreased expression of SIRT1.

Cellular senescence in the lung across the age spectrum

“…Furthermore, in a model of CS-and LPSinduced lung inflammation, knockout of p21 resulted in decreased inflammation and airspace enlargement via NF-B and ROS pathway (192). Within endothelial progenitors with senescent phenotypes, decreased angiogenic potential has been demonstrated in older patients; however, there is a lack of information in this realm with respect to challenges of neonatal life (93). Further, senescence may lead to permissiveness for infectious pathology as one model demonstrated where exposure to SASP from senescent A549 cells increased ligands for pneumococcal bacteria in naive cells, which may lead to detrimental outcomes after discharge from the neonatal intensive care unit (161).…”

Evaluation of potential aging biomarkers in healthy individuals: telomerase, AGEs, GDF11/15, sirtuin 1, NAD+, NLRP3, DNA/RNA damage, and klotho

“…The expression was higher in younger subjects compared to older subjects. Suppression of sirtuin 1 in cells from younger donors induced cell differentiation and senescence (Kaur et al 2018 ). So there are studies that have reported results consistent with ours.…”

Predicting Angiogenesis by Endothelial Progenitor Cells Relying on In-Vitro Function Assays and VEGFR-2 Expression Levels

“…Due to EPCs heterogeneity and the disparate results in different clinical studies, the true identity of these cells remains elusive. For example, Kaur et al [28] isolated EPCs from the peripheral blood of patients with liver cirrhosis. The researchers used isolation and culture protocols similar to ours.…”