Telomere attrition in beta and alpha cells with age

Tamura, Yoshiaki; Izumiyama-Shimomura, Naotaka; Kimbara, Yoshiyuki; Nakamura, Kenichi; Ishikawa, Naoshi; Aida, Junko; Chiba, Yuko; Matsuda, Yoko; Mori, Seijiro; Arai, Tomio; Fujiwara, Mutsunori; Poon, Steven S.S.; Ishizaki, Tatsuro; Araki, Atsushi; Takubo, Kaiyo; Ito, Hideki

doi:10.1007/s11357-016-9923-0

Cited by 11 publications

(5 citation statements)

References 26 publications

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“…As a result of insulin resistance, pancreatic ␤-cell hyperplasia has been observed, which can lead to proliferative exhaustion and senescence of ␤-cells (140,177). Furthermore, the number of pancreatic ␤-cells decreases with age because of a decline in turnover in elderly people (179). Besides a lower number of ␤-cells, senescence of ␤-cells can also lead to a decrease in insulin production in T2DM (180).…”

Section: Pancreatic Cellular Senescencementioning

confidence: 99%

Cellular senescence links aging and diabetes in cardiovascular disease

Shakeri

Lemmens

Gevaert

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

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Aging is a powerful independent risk factor for cardiovascular diseases such as atherosclerosis and heart failure. Concomitant diabetes mellitus strongly reinforces this effect of aging on cardiovascular disease. Cellular senescence is a fundamental mechanism of aging and appears to play a crucial role in the onset and prognosis of cardiovascular disease in the context of both aging and diabetes. Senescent cells are in a state of cell cycle arrest but remain metabolically active by secreting inflammatory factors. This senescence-associated secretory phenotype is a trigger of chronic inflammation, oxidative stress, and decreased nitric oxide bioavailability. A complex interplay between these three mechanisms results in age- and diabetes-associated cardiovascular damage. In this review, we summarize current knowledge on cellular senescence and its secretory phenotype, which might be the missing link between aging and diabetes contributing to cardiovascular disease.

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Section: Pancreatic Cellular Senescencementioning

confidence: 99%

Cellular senescence links aging and diabetes in cardiovascular disease

Shakeri

Lemmens

Gevaert

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

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“… 5 , 21 , 22 , 23 , 24 Our previous study demonstrated that age is an independent risk factor for NODM in patients with idiopathic membranous nephropathy treated with ISDs. 6 Glucose tolerance progressively declines with age, 25 which may be caused by the shortening of telomeres in β and α cells 26 and by age‐related changes in DNA methylation in human islet cells. 27 These two effects may explain the main study finding that older age increased the risk of developing NODM.…”

Section: Resultsmentioning

confidence: 99%

LASSO ‐derived nomogram predicting new‐onset diabetes mellitus in patients with kidney disease receiving immunosuppressive drugs

Shao

Luo

Yuan

et al. 2022

Clinical Pharmacy Therapeu

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What is known and objective Patients with kidney disease receiving immunosuppressive drugs (ISDs) (tacrolimus, cyclosporine and glucocorticoids) have a high risk of developing new‐onset diabetes mellitus (NODM). We aimed to establish a precise and convenient model for predicting NODM in patients receiving immunosuppressive drugs. Methods This retrospective study recruited 1883 patients receiving ISDs between January 2010 and October 2018. The occurrence of NODM was the primary endpoint. The patients were randomly divided into training (n = 1318) and validation cohorts (n = 565) at a 7:3 ratio. A nomogram was established based on a least absolute shrinkage and selection operator (LASSO)‐derived logistic regression model. The nomogram's discrimination and calibration abilities were evaluated in both cohorts using the Hosmer‐Lemeshow test and calibration curves. Decision curve analysis (DCA) was used to evaluate the net benefit of the predictive efficacy. Results and discussion Amongst the 1883 patients with kidney disease receiving immunosuppressive drugs, 375 (28.5%) and 169 (29.9%) developed NODM in the training (n = 1318) and validation cohorts (n = 565), respectively. Nine clinic predictors were included in this LASSO‐derived nomogram, which is easy to be operated clinically. The discriminative ability, determined by the area under the receiver operating characteristic curve (AUC), was 0.816 (95% confidence interval [CI] 0.790–0.841) and 0.831 (95%CI 0.796–0.867) in the training and validation cohorts, respectively. Calibration was confirmed with the Hosmer‐Lemeshow test in the training and validation cohorts (p = 0.238, p = 0.751, respectively). What is new and conclusion Nearly one‐third of patients with kidney disease receiving immunosuppressive drugs developed NODM. The nomogram established in this study may aid in predicting the occurrence of NODM in patients with kidney disease receiving immunosuppressive drugs.

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“…Studies examining the association between α cell mass and age in humans report no drastic changes in α cell mass across time (Henquin & Rahier 2011, Moin et al 2020. However, aged human islet endocrine cells display higher rates of transcriptional noise, increased expression of stress response genes, and shortened telomeres, suggesting that age may influence cell identity and/or function (Tamura et al 2016, Enge et al 2017. Studies of non-human primate α cells support this, where downregulated genes in aged α cells were enriched for gene ontology terms associated with peptide secretion and multiple metabolic processes (Li et al 2020).…”

Section: Agingmentioning

confidence: 99%

The human α cell in health and disease

Pettway

Saunders

2023

Journal of Endocrinology

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In commemoration of 100 years since the discovery of glucagon, we review current knowledge about the human α cell. Alpha cells make up 30-40% of human islet endocrine cells and play a major role in regulating whole-body glucose homeostasis, largely through the direct actions of their main secretory product – glucagon – on peripheral organs. Additionally, glucagon and other secretory products of α cells, namely acetylcholine, glutamate, and GLP-1, have been shown to play an indirect role in the modulation of glucose homeostasis through autocrine and paracrine interactions within the islet. Studies of glucagon’s role as a counterregulatory hormone have revealed additional important functions of the α cell, including the regulation of multiple aspects of energy metabolism outside that of glucose. At the molecular level, human α cells are defined by expression of conserved islet-enriched transcription factors and various enriched signature genes, many of which have currently unknown cellular functions. Despite these common threads, notable heterogeneity exists amongst human α cell gene expression and function. Even greater differences are noted at the interspecies level, underscoring the importance of further study of α cell physiology in the human context. Finally, studies on α cell morphology and function in type 1 and type 2 diabetes, as well as other forms of metabolic stress, reveal a key contribution of α cell dysfunction to dysregulated glucose homeostasis in disease pathogenesis, making targeting the α cell an important focus for improving treatment.

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Telomere attrition in beta and alpha cells with age

Cited by 11 publications

References 26 publications

Cellular senescence links aging and diabetes in cardiovascular disease

Cellular senescence links aging and diabetes in cardiovascular disease

LASSO ‐derived nomogram predicting new‐onset diabetes mellitus in patients with kidney disease receiving immunosuppressive drugs

The human α cell in health and disease

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