The DOI matches its Crossref record; 94 of the 94 references it cites were found in a registry or an index; 1 of the 106 sources its claims cite were checked for support.
Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity
Open accessAbstract
Cellular senescence is a fundamental aging mechanism that has been implicated in many age-related diseases and is a significant cause of tissue dysfunction. Accumulation of senescent cells occurs during aging and is also seen in the context of obesity and diabetes. Senescent cells may play a role in type 2 diabetes pathogenesis through direct impact on pancreatic β-cell function, senescence-associated secretory phenotype (SASP)-mediated tissue damage, and involvement in adipose tissue dysfunction. In turn, metabolic and signaling changes seen in diabetes, such as high circulating glucose, altered lipid metabolism, and growth hormone axis perturbations, can promote senescent cell formation. Thus, senescent cells might be part of a pathogenic loop in diabetes, as both a cause and consequence of metabolic changes and tissue damage. Therapeutic targeting of a basic aging mechanism such as cellular senescence may have a large impact on disease pathogenesis and could be more effective in preventing the progression of diabetes complications than currently available therapies that have limited impact on already existing tissue damage. Therefore, senescent cells and the SASP represent significant opportunities for advancement in the prevention and treatment of type 2 diabetes and its complications.
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Claims the paper makes
70 Not checked yet · 31 Own interpretation · 1 Supported · 1 No basis given
Every source the paper cites for this claim was checked and supports it.
In the paper
“Pancreatic β-cell senescence has been implicated as a contributor to type 2 diabetes, at least in a model of high-fat feeding (63).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence in the Pathogenesis of Type 2 Diabetes > Pancreatic β-Cell Senescence
What the sources say
- Supportedcites [63] Sone, 2005, Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice, Diabetologia source
The Abstract concludes that beta-cell senescence occurred in diet-induced type 2 diabetes and suggests it contributes to its pathogenesis. The Introduction identifies the model as C57BL/6J mice fed a high-fat diet, matching the claim’s qualification. (LLM, conf=0.94)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Supported
In the paper
“Like other age-related chronic diseases, diabetes may be caused in part by a convergence of the basic aging mechanisms that underlie age-related tissue dysfunction, including chronic “sterile” (not pathogen-associated) inflammation, macromolecular damage, progenitor cell dysfunction, and cellular senescence (8).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence: A Basic Aging Mechanism
What the sources say
- Not checked yetcites [8] López-Otín, 2013, The hallmarks of aging, Cell source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In turn, metabolic and signaling changes seen in diabetes, such as high circulating glucose, altered lipid metabolism, and growth hormone axis perturbations, can promote senescent cell formation.”
- Also stated in: § High Glucose · plain
“High glucose drives premature senescence in vitro in endothelial cells, renal mesangial cells, adipose-derived stem cells (also known as preadipocytes or fat cell progenitors), and fibroblasts (35–37).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Abstract
What the sources say
- Not checked yetcites [35] Yokoi, 2006, Apoptosis signal-regulating kinase 1 mediates cellular senescence induced by high glucose in endothelial cells, Diabetes source
- Not checked yetcites [36] Cramer, 2010, Persistent high glucose concentrations alter the regenerative potential of mesenchymal stem cells, Stem Cells Dev source
- Not checked yetcites [37] Blazer, 2002, High glucose-induced replicative senescence: point of no return and effect of telomerase, Biochem Biophys Res Commun source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § High Glucose · plain
None of the sources cited for this claim have been checked yet.
In the paper
“In turn, metabolic and signaling changes seen in diabetes, such as high circulating glucose, altered lipid metabolism, and growth hormone axis perturbations, can promote senescent cell formation.”
- Also stated in: § Growth Hormone/IGF-1 Axis · boosted
“The ability of multiple individual components of this pathway to induce senescence has been recently shown, including growth hormone, IGF-1, and IGF binding protein 5 (IGFBP5) (27,28,41).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Abstract
What the sources say
- Not checked yetcites [27] Stout, 2014, Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice, Aging (Albany, NY Online)
- Not checked yetcites [28] Tran, 2014, Insulin-like growth factor-1 regulates the SIRT1-p53 pathway in cellular senescence, Aging Cell source
- Not checked yetcites [41] Kim, 2007, Induction of cellular senescence by insulin-like growth factor binding protein-5 through a p53-dependent mechanism, Mol Biol Cell source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Growth Hormone/IGF-1 Axis · boosted
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Senescent cells may play a role in type 2 diabetes pathogenesis through direct impact on pancreatic β-cell function, senescence-associated secretory phenotype (SASP)-mediated tissue damage, and involvement in adipose tissue dysfunction.”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Senescent cells may play a role in type 2 diabetes pathogenesis through direct impact on pancreatic β-cell function, senescence-associated secretory phenotype (SASP)-mediated tissue damage, and involvement in adipose tissue dysfunction.”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, senescent cells might be part of a pathogenic loop in diabetes, as both a cause and consequence of metabolic changes and tissue damage.”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Although senescent cells are incapable of dividing, they are metabolically active. This high metabolic activity supports the release of proinflammatory cytokines, chemokines, and growth factors collectively known as the SASP (12,13).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence: A Basic Aging Mechanism
What the sources say
- Not checked yetcites [12] Coppé, 2008, Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor, PLoS Biol source
- Not checked yetcites [13] Kuilman, 2009, Senescence-messaging secretome: SMS-ing cellular stress, Nat Rev Cancer source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Senescent cells may play a role in type 2 diabetes pathogenesis through direct impact on pancreatic β-cell function, senescence-associated secretory phenotype (SASP)-mediated tissue damage, and involvement in adipose tissue dysfunction.”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
In the paper
“Through the SASP, a low absolute number of senescent cells in a tissue (typically <20%) may be able to exert systemic effects (11).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence: A Basic Aging Mechanism
What the sources say
- Not checked yetcites [11] Campisi, 2007, Cellular senescence: when bad things happen to good cells, Nat Rev Mol Cell Biol source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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- It may state two separate claims as one. 28
- Probably not a substantial claim. 13
None of the sources cited for this claim have been checked yet.
In the paper
“Accumulation of senescent cells occurs during aging and is also seen in the context of obesity and diabetes.”
- Also stated in: § Cellular Senescence: A Basic Aging Mechanism · plain
“Senescent cell burden is low in young individuals but increases with aging in several tissues including adipose tissue, skeletal muscle, kidney, and skin (20–22).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Abstract
What the sources say
- Not checked yetcites [20] Tchkonia, 2010, Fat tissue, aging, and cellular senescence, Aging Cell source
- Not checked yetcites [21] Melk, 2005, Increased expression of senescence-associated cell cycle inhibitor p16INK4a in deteriorating renal transplants and diseased native kidney, Am J Transplant source
- Not checked yetcites [22] Waaijer, 2012, The number of p16INK4a positive cells in human skin reflects biological age, Aging Cell source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Cellular Senescence: A Basic Aging Mechanism · plain
In the paper
“Cellular senescence is an essentially irreversible growth arrest that occurs in response to various cellular stressors, such as telomere erosion, DNA damage, oxidative stress, or oncogenic activation, and is thought to have arisen as an antitumor mechanism (11).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence: A Basic Aging Mechanism
What the sources say
- Not checked yetcites [11] Campisi, 2007, Cellular senescence: when bad things happen to good cells, Nat Rev Mol Cell Biol source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In addition to growth arrest, senescent cells adopt several unique identifying characteristics, including a flattened morphology in culture, upregulation of cell cycle inhibitors such as p21 and p16, accumulation of DNA damage foci, reactive oxygen species production, and shifted optimum pH of lysosomal β-galactosidase (senescence-associated β-galactosidase [SA-βgal] activity) (11).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence: A Basic Aging Mechanism
What the sources say
- Not checked yetcites [11] Campisi, 2007, Cellular senescence: when bad things happen to good cells, Nat Rev Mol Cell Biol source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Senescent cell burden is low in young individuals but increases with aging in several tissues including adipose tissue, skeletal muscle, kidney, and skin (20–22).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence: A Basic Aging Mechanism
What the sources say
- Not checked yetcites [20] Tchkonia, 2010, Fat tissue, aging, and cellular senescence, Aging Cell source
- Not checked yetcites [21] Melk, 2005, Increased expression of senescence-associated cell cycle inhibitor p16INK4a in deteriorating renal transplants and diseased native kidney, Am J Transplant source
- Not checked yetcites [22] Waaijer, 2012, The number of p16INK4a positive cells in human skin reflects biological age, Aging Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Cellular senescence is an essentially irreversible growth arrest that occurs in response to various cellular stressors, such as telomere erosion, DNA damage, oxidative stress, or oncogenic activation, and is thought to have arisen as an antitumor mechanism (11).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence: A Basic Aging Mechanism
What the sources say
- Not checked yetcites [11] Campisi, 2007, Cellular senescence: when bad things happen to good cells, Nat Rev Mol Cell Biol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Although cellular senescence is normally a defense mechanism against tumor development, presence or persistence of a high number of senescent cells can promote tumor progression because of inflammation, tissue disruption, and growth signals due to the SASP (16).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence: A Basic Aging Mechanism
What the sources say
- Not checked yetcites [16] Campisi, 2005, Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors, Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Cellular senescence is a fundamental aging mechanism that has been implicated in many age-related diseases and is a significant cause of tissue dysfunction.”
- Also stated in: § Cellular Senescence: A Basic Aging Mechanism · hedged
“In the past decade, cellular senescence has emerged as a possible cause of general tissue dysfunction and aging phenotypes (9,10).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Abstract
What the sources say
- Not checked yetcites [9] Kirkland, Clinical strategies and animal models for developing senolytic agents, Exp Gerontol. 28 October 2015 [Epub ahead of print]. DOI
- Not checked yetcites [10] Muñoz-Espín, 2014, Cellular senescence: from physiology to pathology, Nat Rev Mol Cell Biol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Cellular Senescence: A Basic Aging Mechanism · hedged
In the paper
“The aging microenvironment limits regenerative potential of young progenitor cells in vivo, and conversely, aged progenitor cells exhibit improved function when exposed to a young systemic microenvironment (68).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence in the Pathogenesis of Type 2 Diabetes > Senescence and Diabetes Complications
What the sources say
- Not checked yetcites [68] Conboy, 2005, Rejuvenation of aged progenitor cells by exposure to a young systemic environment, Nature source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The cell cycle inhibitor p27, a marker of senescence, increases in pancreatic β-cells in genetic mouse models of type 2 diabetes, and p27 deletion in those mice increased insulin secretion and islet mass through increased proliferation (64).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence in the Pathogenesis of Type 2 Diabetes > Pancreatic β-Cell Senescence
What the sources say
- Not checked yetcites [64] Uchida, 2005, Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice, Nat Med source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In mice lacking p53-dependent apoptosis, the burden of senescent cells increases rapidly and is associated with dysfunction of pancreatic β-cells, causing an overt diabetic phenotype in 3–4 months (65).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence in the Pathogenesis of Type 2 Diabetes > Pancreatic β-Cell Senescence
What the sources say
- Not checked yetcites [65] Tavana, 2010, Absence of p53-dependent apoptosis combined with nonhomologous end-joining deficiency leads to a severe diabetic phenotype in mice, Diabetes source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Senescent cell accumulation can occur due to a variety of factors, such as various age-related chronic diseases, oxidative stress, the hormonal milieu, developmental factors, chronic infection (e.g., HIV), certain medications (e.g., chemotherapy or certain HIV protease inhibitors), and radiation exposure (9,10,27,28).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence: A Basic Aging Mechanism
What the sources say
- Not checked yetcites [9] Kirkland, Clinical strategies and animal models for developing senolytic agents, Exp Gerontol. 28 October 2015 [Epub ahead of print]. DOI
- Not checked yetcites [10] Muñoz-Espín, 2014, Cellular senescence: from physiology to pathology, Nat Rev Mol Cell Biol source
- Not checked yetcites [27] Stout, 2014, Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice, Aging (Albany, NY Online)
- Not checked yetcites [28] Tran, 2014, Insulin-like growth factor-1 regulates the SIRT1-p53 pathway in cellular senescence, Aging Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Cardiac progenitor aging is accelerated in diabetes, and heart disease is a major complication of diabetes (74).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence in the Pathogenesis of Type 2 Diabetes > Senescence and Diabetes Complications
What the sources say
- Not checked yetcites [74] Rota, 2006, Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66shc gene, Circ Res source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Components of the SASP, such as interleukin (IL)-6, IL-8, and MCP-1, are increased in obese adults and adolescents and could contribute to such a proinflammatory state, together with effects of macrophages and other mediators of inflammation (31,53,54).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence in the Pathogenesis of Type 2 Diabetes > SASP: Mediator of Insulin Resistance?
What the sources say
- Not checked yetcites [31] Freund, 2010, Inflammatory networks during cellular senescence: causes and consequences, Trends Mol Med source
- Not checked yetcites [53] Kim, 2006, Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters, Int J Obes (Lond) source
- Not checked yetcites [54] Utsal, 2012, Elevated serum IL-6, IL-8, MCP-1, CRP, and IFN-γ levels in 10- to 11-year-old boys with increased BMI, Horm Res Paediatr source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is possible that senescent cells are a contributor to the aging microenvironment, which may limit the regenerative potential of cells in every tissue.”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence in the Pathogenesis of Type 2 Diabetes > Senescence and Diabetes Complications
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In addition, overexpression of IGFBP3 in mice leads to decreased glucose tolerance, insulin resistance, and hyperglycemia (46).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Diabetic Microenvironment Promotes Cellular Senescence > Growth Hormone/IGF-1 Axis
What the sources say
- Not checked yetcites [46] Silha, 2002, Impaired glucose homeostasis in insulin-like growth factor-binding protein-3-transgenic mice, Am J Physiol Endocrinol Metab source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Several possible “subtypes” of cellular senescence have been identified, including oncogene-induced senescence, stress-induced premature senescence, and the classical replicative senescence (10).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence: A Basic Aging Mechanism
What the sources say
- Not checked yetcites [10] Muñoz-Espín, 2014, Cellular senescence: from physiology to pathology, Nat Rev Mol Cell Biol source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Chronic, sterile, low-grade inflammation is associated with both obesity and aging and is thought to be a major contributing factor for the development of insulin resistance (Fig. 1) (14,52).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence in the Pathogenesis of Type 2 Diabetes > SASP: Mediator of Insulin Resistance?
What the sources say
- Not checked yetcites [14] Esser, 2014, Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes, Diabetes Res Clin Pract source
- Not checked yetcites [52] Xu, 2003, Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance, J Clin Invest source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Increased senescent preadipocytes could contribute to declines in adipogenic and lipogenic potential, with consequent development of age-related lipodystrophy, leading to lipotoxicity and inflammation (20).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence in the Pathogenesis of Type 2 Diabetes > Cellular Senescence and Adipose Tissue Dysfunction
What the sources say
- Not checked yetcites [20] Tchkonia, 2010, Fat tissue, aging, and cellular senescence, Aging Cell source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Other related factors, such as IGFBP3, have been implicated as SASP components that may play a role in the propagation of senescence signals to neighboring cells (42).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Diabetic Microenvironment Promotes Cellular Senescence > Growth Hormone/IGF-1 Axis
What the sources say
- Not checked yetcites [42] Elzi, 2012, Plasminogen activator inhibitor 1—insulin-like growth factor binding protein 3 cascade regulates stress-induced senescence, Proc Natl Acad Sci U S A source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, inhibition of de novo ceramide synthesis in diet-induced obese and ob/ob mice has been shown to decrease the SASP factors PAI-1 and MCP-1 and improve metabolic phenotypes such as glucose and insulin tolerance (51).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Diabetic Microenvironment Promotes Cellular Senescence > Ceramides
What the sources say
- Not checked yetcites [51] Yang, 2009, Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome, Am J Physiol Endocrinol Metab source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Microvascular complications of diabetes, such as retinopathy, neuropathy, and nephropathy, could be linked to cellular senescence as well, as endothelial cells have been shown to be susceptible to glucose-induced senescence (35).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence in the Pathogenesis of Type 2 Diabetes > Senescence and Diabetes Complications
What the sources say
- Not checked yetcites [35] Yokoi, 2006, Apoptosis signal-regulating kinase 1 mediates cellular senescence induced by high glucose in endothelial cells, Diabetes source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The ability of multiple individual components of this pathway to induce senescence has been recently shown, including growth hormone, IGF-1, and IGF binding protein 5 (IGFBP5) (27,28,41).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Diabetic Microenvironment Promotes Cellular Senescence > Growth Hormone/IGF-1 Axis
What the sources say
- Not checked yetcites [27] Stout, 2014, Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice, Aging (Albany, NY Online)
- Not checked yetcites [28] Tran, 2014, Insulin-like growth factor-1 regulates the SIRT1-p53 pathway in cellular senescence, Aging Cell source
- Not checked yetcites [41] Kim, 2007, Induction of cellular senescence by insulin-like growth factor binding protein-5 through a p53-dependent mechanism, Mol Biol Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Case-control studies have found that elevated IL-6 and the combined elevation of IL-6 and IL-1β, both SASP factors, are independent predictors of diabetes (55,56).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence in the Pathogenesis of Type 2 Diabetes > SASP: Mediator of Insulin Resistance?
What the sources say
- Not checked yetcites [55] Pradhan, 2001, C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus, JAMA source
- Not checked yetcites [56] Spranger, 2003, Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study, Diabetes source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In turn, features of diabetes may cause an increase in senescent cell number, which would further promote chronic inflammation and initiate a vicious cycle of senescent cell formation in multiple tissues.”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By removing senescent cells or their systemic effects, it may be possible to both halt the progression of diabetic tissue damage as well as to improve insulin sensitivity.”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Therapeutic Targeting of Senescent Cells > Feasibility of Senescence as a Therapeutic Target
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Cellular senescence can be accompanied by mitochondrial dysfunction that, in turn, causes oxidative stress, which has been implicated as a cause of insulin resistance in muscle tissue with aging (78,79).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Cellular Senescence in the Pathogenesis of Type 2 Diabetes > Cellular Senescence Establishes Pathogenic Positive Feedback Loops in Diabetes
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“It has been suggested that senescent cells are cleared by the immune system, but the specific immune cell types involved and the kinetics of clearance are unknown (83).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Therapeutic Targeting of Senescent Cells > Feasibility of Senescence as a Therapeutic Target
What the sources say
- Not checked yetcites [83] Xue, 2007, Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas, Nature source
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We hypothesize that clearing senescent cells or targeting the SASP may present opportunities for the development of revolutionary therapies for diabetes and its complications.”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“For example, the cytokine IL-6 is an important component of the SASP and appears to be an indicator of frailty (92).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Therapeutic Targeting of Senescent Cells > Feasibility of Senescence as a Therapeutic Target
What the sources say
- Not checked yetcites [92] Leng, 2002, Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study, J Am Geriatr Soc source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Existing diabetes therapies, namely metformin and acarbose, extend lifespan in nondiabetic mice (86,87).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Therapeutic Targeting of Senescent Cells > Do Current Diabetes Therapies Affect Senescence?
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Developing strategies to increase lifespan or healthspan, such as strategies that target cellular senescence and the SASP, is challenging due to the impractical nature of the required clinical trials.”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Therapeutic Targeting of Senescent Cells > Feasibility of Senescence as a Therapeutic Target
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Many studies have drawn associations between cellular senescence and disease states, such as renal tubular senescence in diabetes; however, the timeline for senescent cell appearance is unclear (67).”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Therapeutic Targeting of Senescent Cells > Feasibility of Senescence as a Therapeutic Target
What the sources say
- Not checked yetcites [67] Verzola, 2008, Accelerated senescence in the kidneys of patients with type 2 diabetic nephropathy, Am J Physiol Renal Physiol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This may be because much damage occurs before diagnosis and initiation of treatment.”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Senescent cell burden increases in aging and obesity”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Shared mechanisms between the development of insulin resistance and cellular senescence indicate that perhaps by clearing senescent cells, both the metabolic components and complications of diabetes could be ameliorated.”
§ Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Current therapies for type 2 diabetes have limited efficacy in slowing disease progression and complications.
“Despite increased understanding of the pathogenesis of diabetes and its comorbidities, current therapies have limited efficacy with respect to its progression and complications.”
The paper relies on this without support.
Metformin improves diabetes, its complications and the metabolic syndrome.
“Metformin alleviates diabetes, diabetes complications, and the metabolic syndrome.”
The paper relies on this without support.
The composition of the senescence-associated secretory phenotype differs by cell type, tissue type and organism, and its factors have several roles in inflammation, immunity and normal physiology.
“This issue is complicated by cell-type, tissue-type, and organismal differences in the composition of the SASP, as well as the multiple effects that SASP factors can play in inflammation, immunity, and normal physiology.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“For example, elevated glucose and lipid levels themselves, like inflammation, can induce cellular senescence [11, 37].”
From Cellular senescence: at the nexus between ageing and diabetes (2019) · cites this paper as [11]
In the citing paper
“various cardiovascular risk factors including obesity, hypertension, diabetes and atherosclerosis that compromise metabolism are associated with an inflammatory state and increased cellular senescence and SASP”
From Redox control of senescence and age-related disease. (2017) · cites this paper as [96]
In the citing paper
“Obese individuals with type-2 diabetes show increased levels of SASP factors IL-6, IL-8, and the chemokine MCP-1”
From Redox control of senescence and age-related disease. (2017) · cites this paper as [96]
In the citing paper
“both IL-6 and IL-1β are independent predictors of diabetes”
From Redox control of senescence and age-related disease. (2017) · cites this paper as [96]
In the citing paper
“Obesity is thought to promote cell senescence through various means including oxidative stress, high glucose concentrations in the microenvironment, and increased IGF and ceramides (104).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [104]
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Metadata
- Authors
- Palmer, A. K., Tchkonia, T., LeBrasseur, N. K., Chini, E. N., Xu, M., & Kirkland, J. L.
- Affiliations
- Mayo Clinic (US)
- Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN
- Corresponding author
- Kirkland, James L.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2015-06-17
- Volume
- 64
- Issue
- 7
- Pages
- 2289-2298
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC4477358
- OpenAlex
- W1908141864
- Semantic Scholar
- 85b2a4f3a4cebcc4dbbf69fcf3bd383219229501
- Cited by
- 423
- References
- 94
- Citations by year
- 2026: 33 · 2025: 32 · 2024: 47 · 2023: 33 · 2022: 62 · 2021: 47 · 2020: 48 · 2019: 41 · 2018: 29 · 2017: 27 · 2016: 18 · 2015: 4
- FWCI
- 3.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Noaber Foundation
- Glenn Foundation for Medical Research
- National Institute on Aging (AG044396, AG046061)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- cellular senescence, type 2 diabetes, senescence-associated secretory phenotype, beta-cell dysfunction, adipose tissue dysfunction, aging, obesity, growth hormone axis, diabetes complications, senolytics
- MeSH terms
- Adipose Tissue, Animals, Ceramides, Diabetes Mellitus, Type 2, Humans, Insulin Resistance, Insulin-Like Growth Factor I, Cellular Senescence, Insulin-Like Growth Factor Binding Protein 3, Insulin-Secreting Cells, Cellular Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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