NMR-based metabonomic analysis of HUVEC cells during replicative senescence

Abstract

Cellular senescence is a physiological process reacting to stimuli, in which cells enter a state of irreversible growth arrest in response to adverse consequences associated with metabolic disorders. Molecular mechanisms underlying the progression of cellular senescence remain unclear. Here, we established a replicative senescence model of human umbilical vein endothelial cells (HUVEC) from passage 3 (P3) to 18 (P18), and performed biochemical characterizations and NMR-based metabolomic analyses. The cellular senescence degree advanced as the cells were sequentially passaged in vitro, and cellular metabolic profiles were gradually altered. Totally, 8, 16, 21 and 19 significant metabolites were primarily changed in the P6, P10, P14 and P18 cells compared with the P3 cells, respectively. These metabolites were mainly involved in 14 significantly altered metabolic pathways. Furthermore, we observed taurine retarded oxidative damage resulting from senescence. In the case of energy deficiency, HUVECs metabolized neutral amino acids to replenish energy, thus increased glutamine, aspartate and asparagine at the early stages of cellular senescence but decreased them at the later stages. Our results indicate that cellular replicative senescence is closely associated with promoted oxidative stress, impaired energy metabolism and blocked protein synthesis. This work may provide mechanistic understanding of the progression of cellular senescence.

Cellular aging beyond cellular senescence: Markers of senescence prior to cell cycle arrest in vitro and in vivo

“…Another metabolic feature of cellular aging observed by Yi et al was a gradual decline in NAD + concentration in cultures of cells approaching the Hayflick limit (Yi et al, 2020). This is in agreement with research on human primary and cancer cells, showing that conditions characterized by a reduction in NAD + levels prevent cell proliferation (Chini et al, 2014; van der Veer et al, 2007; Zhang et al, 2002).…”

“…Certain studies were able, however, to use other approaches to characterize progression of metabolic changes occurring in primary cells during cellular aging. In a recent study, Yi et al performed nuclear magnetic resonance (NMR) analysis of intracellular metabolites from five different time points (PD 4,15,31,46, and 61) of human primary cells and observed a gradual decline in the levels of several metabolites including glutamate (product of glutaminolysis) and lactate (Yi et al, 2020). At the same time, the levels of glutamine increased, but the glucose levels did not change (Yi et al, 2020).…”

“…In a recent study, Yi et al performed nuclear magnetic resonance (NMR) analysis of intracellular metabolites from five different time points (PD 4,15,31,46, and 61) of human primary cells and observed a gradual decline in the levels of several metabolites including glutamate (product of glutaminolysis) and lactate (Yi et al, 2020). At the same time, the levels of glutamine increased, but the glucose levels did not change (Yi et al, 2020). These observations can already be related to the requirements for cell proliferation (reviewed in (Lunt & Vander Heiden, 2011)); however, in order to fully understand their impact, it would be necessary to examine the metabolic profile of senescent cells.…”

Nutrition Interventions of Herbal Compounds on Cellular Senescence

“…Recently, metabolomics analysis on human umbilical vein endothelial cells (HUVECs) was carried out, from the third to eighteenth population doublings, and enriched 14 overtly changed metabolic pathways in senescent cells [ 21 ]. This work provided a new perspective to understand the mechanism of cell senescence.…”

A comprehensive analysis of age-related metabolomics and transcriptomics reveals metabolic alterations in rat bone marrow mesenchymal stem cells

“…Aging is closely related to disturbance in the maintenance of metabolism. With cellular senescence, a AGING large number of neutral amino acids such as valine, isoleucine and glycine may be used as alternative energy sources to maintain energy homeostasis [7]. Some studies reported that the anti-aging mechanisms of C. elegans and rats may be related to the regulation of lipid metabolism [8,9], and lipids can modulate the biological characteristics of stem cells by influencing energy storage, plasma membrane composition, signal transduction and gene expression changes [10].…”