Acceleration of β Cell Aging Determines Diabetes and Senolysis Improves Disease Outcomes

Aguayo-Mazzucato, Cristina; Andle, Joshua; Lee, Terrence B.; Midha, Ayush; Talemal, Lindsay; Chipashvili, Vaja; Hollister-Lock, Jennifer; Deursen, Jan van; Weir, Gordon C.; Bonner-Weir, Susan

doi:10.1016/j.cmet.2019.05.006

Cited by 349 publications

(441 citation statements)

References 58 publications

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“…In addition to acquiring an oftentimes complex SASP, senescent cells can display a variety of biomarkers, including profound changes in heterochromatin (i.e., SADS) (27), DNA damage colocalized with telomeres (i.e., TAF) (28), and increased expression of the cyclin-dependent kinase inhibitors p16 Ink4a and p21 Cip1 (21). Accelerated accumulation of senescent cells has been identified in mice during obesity in adipose tissue, liver, and brain (13)(14)(15) and with T2D in the pancreas (e.g., senescent β cells) (16). In the latter study, HFD-induced obesity and insulin resistance in mice caused accelerated β cell senescence with a specific SASP, whereas senolysis (i.e., clearance of senescent cells) using either genetic or pharmacological approaches improved glucose homeostasis, β cell function, and the gene expression profile of β cells (16).…”

Section: Discussionmentioning

confidence: 99%

“…We have previously identified senescent cells in the bone microenvironment with aging (11) and found that targeting cellular senescence improved age-related bone loss (12). Furthermore, senescence has been shown to increase in adipose tissue, liver, and brain during obesity (13)(14)(15) and in pancreatic β cells, contributing to T2D (16). This led us to hypothesize that cellular senescence may be a mechanistic link between poor bone quality and T2D.…”

Section: Introductionmentioning

confidence: 99%

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Accelerated osteocyte senescence and skeletal fragility in mice with type 2 diabetes

Eckhardt¹,

Rowsey²,

Thicke³

et al. 2020

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Accelerated osteocyte senescence and skeletal fragility in mice with type 2 diabetes

Eckhardt¹,

Rowsey²,

Thicke³

et al. 2020

JCI Insight

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“…A recent study has shown that insulin resistance accelerates β‐cell senescence and ageing in mice, leading to insulin secretory defects. Senolytic therapies, which specifically target senescent cells while sparing nonsenescent ones, improve the metabolic profile of different models of rodent insulin resistance and improve β‐cell function and gene expression profile …”

Section: Pathophysiology Of T2dmentioning

confidence: 99%

“…Senolytic therapies, which specifically target senescent cells while sparing nonsenescent ones, improve the metabolic profile of different models of rodent insulin resistance and improve β-cell function and gene expression profile. 83 Isolated β-cell function studies in the MA population are difficult to perform but are necessary to elucidate mechanisms behind the increased incidence and prevalence of T2D in this population.…”

Section: β-Cell Function and Senescencementioning

confidence: 99%

Understanding the growing epidemic of type 2 diabetes in the Hispanic population living in the United States

Aguayo-Mazzucato

Diaque

Hernandez

et al. 2018

Diabetes Metabolism Res

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159

130

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Summary The prevalence and incidence of type 2 diabetes (T2D) among the Hispanic population in the United States are higher than the national average. This is partly due to sociocultural factors, such as lower income and decreased access to education and health care, as well as a genetic susceptibility to obesity and higher insulin resistance. This review focuses on understanding the Hispanic population living in the United States from a multidisciplinary approach and underlines the importance of cultural, social, and biological factors in determining the increased risk of T2D in this population. An overview of the acute and chronic complications of T2D upon this population is included, which is of paramount importance to understand the toll that diabetes has upon this population, the health system, and society as a whole. Specific interventions directed to the Hispanic populations are needed to prevent and alleviate some of the burdens of T2D. Different prevention strategies based on medications, lifestyle modifications, and educational programmes are discussed herein. Diabetes self‐management education (DSME) is a critical element of care of all people with diabetes and is considered necessary to improve patient outcomes. To be more effective, programmes should take into consideration cultural factors that influence the development and progression of diabetes. These interventions aim to enhance long‐term effects by reducing the incidence, morbidity, and mortality of T2D in the Hispanic population of the United States.

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“…For example, it has been shown that β cells become senescent during the progression of Type I and Type II diabetes. Clearance of senescent β cells effectively restored β cell function and glucose homeostasis . Furthermore, ablation of senescent cells by transgenic clearance or treatment with senolytics improved pulmonary function and physical health in a murine model of idiopathic pulmonary fibrosis, a chronic respiratory disease the incident of which increases with aging .…”

Section: Organismal Aging and Cellular Senescencementioning

confidence: 58%

Organismal Aging and Oxidants beyond Macromolecules Damage

Clément

Luo

2020

Proteomics

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The relationship between oxidants and organismal aging was first articulated through the free radical theory of aging. One of the major predictions of the free radical theory of aging is that oxidative stress shortens organisms’ lifespan because of an increased level of oxidants, which are damaging to macromolecules. However, challenging the role of oxidants in age‐related diseases, there is now sufficient evidence that antioxidant supplements do not provide significant health benefits. Interestingly, in addition to an increase in oxidant‐mediated macromolecules damage, there is convincing experimental data to support the role of senescent cells in the process of aging. Here, the current knowledge regarding the role of oxidants and cellular senescence in organismal aging is reviewed and it is proposed that, in addition to the role of oxidants as inducers of macromolecular damage, oxidants may also function as regulators of signaling pathways involved in the establishment of cellular senescence. If this role for oxidants is established, it may be necessary to modify the free radical theory of aging from “Organisms age because cells accumulate reactive oxygen species‐dependent damage over time” to: “Organisms age because cells accumulate oxidants’‐dependent damage and oxidants’‐dependent senescent characteristics over time.”

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Acceleration of β Cell Aging Determines Diabetes and Senolysis Improves Disease Outcomes

Cited by 349 publications

References 58 publications

Accelerated osteocyte senescence and skeletal fragility in mice with type 2 diabetes

Accelerated osteocyte senescence and skeletal fragility in mice with type 2 diabetes

Understanding the growing epidemic of type 2 diabetes in the Hispanic population living in the United States

Organismal Aging and Oxidants beyond Macromolecules Damage

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