High glucose-induced replicative senescence: point of no return and effect of telomerase

Blazer, Shraga; Khankin, Eliyahu V.; Segev, Yardena; Ofir, Rachel; Yalon-Hacohen, Michal; Kra-Oz, Zipora; Gottfried, Yossi; Larisch, Sarit; Skorecki, Karl

doi:10.1016/s0006-291x(02)00818-5

Cited by 99 publications

(67 citation statements)

References 34 publications

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“…Moreover, accelerated loss of HPMC proliferative capacity was associated with the increased presence of a senescence marker, SA-b-Gal. In this respect, our results are in line with those of Blazer et al, 26 who observed premature senescence of skin fibroblasts propagated in elevated glucose. Moreover, our results are in keeping with the observations of Gotloib et al, who detected the appearance of mesothelial cells with the senescent-like phenotype in mice treated chronically with high intraperitoneal load of glucose.…”

Section: Discussionsupporting

confidence: 93%

Accelerated senescence of human peritoneal mesothelial cells exposed to high glucose: the role of TGF-β1

Książek

Korybalska

Jörres

et al. 2007

Laboratory Investigation

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Cellular senescence can be activated in response to noxious environmental stimuli. A senescent-like phenotype has been detected in the peritoneal mesothelium of mice exposed to high intraperitoneal glucose. We have sought to examine whether high glucose (HG) can induce the senescence program in human peritoneal mesothelial cells (HPMC) in vitro. Senescence of omentum-derived HPMC was induced by serial passages. Cells were cultured in media containing either 5 mM glucose, 30 mM glucose, or 5 mM glucose and 25 mM mannitol (M) for osmotic control. Compared with HPMC cultured in low glucose, the growth rate of cells exposed to HG was significantly decreased so that the cells reached fewer population doublings before entering senescence. Exposure to HG led to increased expression of senescence-associated b-galactosidase (SA-b-Gal) and of the cell cycle inhibitors p21 Waf1 and p27 Kip1 . Late-passage HPMC exposed to HG displayed marked hypertrophy and released increased amounts of fibronectin and TGF-b1. These effects were absent from HPMC treated with equimolar M. Exposure of early-passage HPMC to exogenous recombinant TGF-b1 induced a senescence marker SA-b-Gal in a dose-dependent manner and mimicked other senescence-associated alterations induced by HG. The addition of anti-TGF-b1 neutralizing antibody partially reduced the activation of HG-induced SA-b-Gal. These results indicate that chronic exposure to elevated glucose may result in TGF-b1-mediated accelerated senescence of HPMC in vitro, which may hypothetically contribute to the peritoneal membrane dysfunction during peritoneal dialysis in vivo.

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Section: Discussionsupporting

confidence: 93%

Accelerated senescence of human peritoneal mesothelial cells exposed to high glucose: the role of TGF-β1

Książek

Korybalska

Jörres

et al. 2007

Laboratory Investigation

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“…The Metabolic Syndrome, through obesity or insulin resistance, may accelerate cell aging processes by causing, for example, greater exposure to hyperglycemia (Blazer et al, 2002), insulin (Gardner et al, 2005) and oxidative stress associated with insulin resistance (Davi et al, 2005). Given the relations we report here between one-time measurement of leukocyte telomerase activity level and stable factors such as one's body mass and cholesterol, it appears as if snap-shot telomerase levels reflect relatively stable levels over time.…”

Section: Cvd Processes Decreasing Telomerasementioning

confidence: 67%

Cell aging in relation to stress arousal and cardiovascular disease risk factors

Epel¹,

Lin²,

Wilhelm

et al. 2006

Psychoneuroendocrinology

395

303

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SummaryWe previously reported that psychological stress is linked to and possibly accelerates cellular aging, as reflected by lower PBMC telomerase and shortened telomeres. Psychological stress is a major risk factor for cardiovascular disease (CVD), with multiple behavioral and physiological mediators. Telomere shortness has been associated with CVD, but the relationship between low telomerase activity, a potential precursor to telomere shortening, and CVD risk factors has not been examined in humans. Here we examine whether telomere length and telomerase in leukocytes are associated with physiological signs of stress arousal and CVD risk factors in 62 healthy women. Low telomerase activity in leukocytes was associated with exaggerated autonomic reactivity to acute mental stress and elevated nocturnal epinephrine. Further, low telomerase activity was associated with the major risk factors for CVD -smoking, poor lipid profile, high systolic blood pressure, high fasting glucose, greater abdominal adiposity-as well as to a composite Metabolic Syndrome variable. Telomere length was related only to elevated stress hormones (catecholamines and cortisol). Thus, we propose that low leukocyte telomerase constitutes an early marker of CVD risk, possibly preceding shortened telomeres, that results in part from chronic stress arousal. Possible cellular mechanisms by which low telomerase may link stress and traditional risk factors to CVD are discussed. Psychoneuroendocrinology (2006) These findings may implicate telomerase as a novel and important mediator of the effects of psychological stress on physical health and disease. Q

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“…Cells were cultured under different conditions: Normal glucose (NG; 5.5 mmol/L) 16) ; normal glucose plus resveratrol (NGR; normal glucose medium supplemented with 1.4 µg/mL resveratrol), high glucose (HG; 25 mmol/L), 17) or high glucose plus resveratrol (HGR; high glucose medium supplemented with 1.4 µg/mL resveratrol). Resveratrol (Sigma) suspended in dimethyl sulfoxide (DMSO) was used in the in vitro study.…”

Section: Animals and Treatmentmentioning

confidence: 99%

Resveratrol Protects against High-Fat Diet Induced Renal Pathological Damage and Cell Senescence by Activating SIRT1

Zhang

et al. 2016

Biological & Pharmaceutical Bulletin

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Obesity-related renal diseases have been a worldwide issue. Effective strategy that prevents high fat-diet induced renal damage is of great significance. Resveratrol, a natural plant polyphenol, is famous for its antioxidant activity, cardioprotective effects and anticancer properties. However whether resveratrol can play a role in the treatment of renal diseases is unknown. In this study, we added resveratrol in normal glucose or high glucose medium and provide evidences that resveratrol protects against high-glucose triggered oxidative stress and cell senescence. Moreover, mice were fed with standard diet, standard diet plus resveratrol, high-fat diet or high-fat diet plus resveratrol for 3 months, and results show that resveratrol treatment prevents high-fat diet induced renal pathological damage by activating SIRT1, a key member in the mammalian sirtuin family that response to calorie restriction life-extension method. This research confirms the potential role of resveratrol in the treatment of renal diseases and may provide an effective and convenient method to mimic the beneficial effects of calorie restriction.

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High glucose-induced replicative senescence: point of no return and effect of telomerase

Cited by 99 publications

References 34 publications

Accelerated senescence of human peritoneal mesothelial cells exposed to high glucose: the role of TGF-β1

Accelerated senescence of human peritoneal mesothelial cells exposed to high glucose: the role of TGF-β1

Cell aging in relation to stress arousal and cardiovascular disease risk factors

Resveratrol Protects against High-Fat Diet Induced Renal Pathological Damage and Cell Senescence by Activating SIRT1

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