Allyson K. Palmer
Mayo Clinic
EndocrinologyAdipose tissueSenolyticDiabetes mellitusBiology
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Publications 21
#2Tomás P. GriffinH-Index: 7
Last. LaTonya J. Hickson (Mayo Clinic)H-Index: 18
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Objective Activin A, an inflammatory mediator implicated in cellular senescence-induced adipose tissue dysfunction and profibrotic kidney injury, may become a new target for the treatment of diabetic kidney disease (DKD) and chronic kidney diseases. We tested the hypothesis that human DKD-related injury leads to upregulation of activin A in blood and urine and in a human kidney cell model. We further hypothesized that circulating activin A parallels kidney injury markers in DKD. Research design ...
#1Allyson K. Palmer (Mayo Clinic)H-Index: 13
#2Birgit Gustafson (Sahlgrenska University Hospital)H-Index: 19
Last. Ulf Smith (Sahlgrenska University Hospital)H-Index: 86
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Ageing and diabetes lead to similar organ dysfunction that is driven by parallel molecular mechanisms, one of which is cellular senescence. The abundance of senescent cells in various tissues increases with age, obesity and diabetes. Senescent cells have been directly implicated in the generation of insulin resistance. Recently, drugs that preferentially target senescent cells, known as senolytics, have been described and recently entered clinical trials. In this review, we explore the biologica...
11 CitationsSource
#1Allyson K. Palmer (Mayo Clinic)H-Index: 13
#2Ming Xu (UConn: University of Connecticut)H-Index: 22
Last. James L. KirklandH-Index: 59
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Adipose tissue inflammation and dysfunction are associated with obesity-related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug-inducible "suicide" genes driven by the p16(Ink4a) promo...
12 CitationsSource
#1Mikolaj Ogrodnik (Newcastle University)H-Index: 15
#2Yi Zhu (Mayo Clinic)H-Index: 17
Last. Diana Jurk (Newcastle University)H-Index: 25
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Summary Cellular senescence entails a stable cell-cycle arrest and a pro-inflammatory secretory phenotype, which contributes to aging and age-related diseases. Obesity is associated with increased senescent cell burden and neuropsychiatric disorders, including anxiety and depression. To investigate the role of senescence in obesity-related neuropsychiatric dysfunction, we used the INK-ATTAC mouse model, from which p16 Ink4a -expressing senescent cells can be eliminated, and senolytic drugs dasat...
16 CitationsSource
#1Mikolaj OgrodnikH-Index: 15
#2Yi ZhuH-Index: 17
Last. Tamar PirtskhalavaH-Index: 27
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14 CitationsSource
#1Ming Xu (UConn: University of Connecticut)H-Index: 22
#2Tamar Pirtskhalava (Mayo Clinic)H-Index: 27
Last. James L. Kirkland (Mayo Clinic)H-Index: 59
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Physical function declines in old age, portending disability, increased health expenditures, and mortality. Cellular senescence, leading to tissue dysfunction, may contribute to these consequences of aging, but whether senescence can directly drive age-related pathology and be therapeutically targeted is still unclear. Here we demonstrate that transplanting relatively small numbers of senescent cells into young mice is sufficient to cause persistent physical dysfunction, as well as to spread cel...
155 CitationsSource
#1Mikolaj Ogrodnik (Newcastle University)H-Index: 15
#2Satomi Miwa (Newcastle University)H-Index: 26
Last. Diana Jurk (Newcastle University)H-Index: 25
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The incidence of non-alcoholic fatty liver disease (NAFLD) increases with age. Cellular senescence refers to a state of irreversible cell-cycle arrest combined with the secretion of proinflammatory cytokines and mitochondrial dysfunction. Senescent cells contribute to age-related tissue degeneration. Here we show that the accumulation of senescent cells promotes hepatic fat accumulation and steatosis. We report a close correlation between hepatic fat accumulation and markers of hepatocyte senesc...
126 CitationsSource
#1Michael B. Stout (Mayo Clinic)H-Index: 16
#2Frederik J. Steyn (UQ: University of Queensland)H-Index: 21
Last. James L. Kirkland (Mayo Clinic)H-Index: 59
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Aging is associated with visceral adiposity, metabolic disorders, and chronic low-grade inflammation. 17α-estradiol (17α-E2), a naturally occurring enantiomer of 17α-estradiol (17α-E2), extends life span in male mice through unresolved mechanisms. We tested whether 17α-E2 could alleviate age-related metabolic dysfunction and inflammation. 17α-E2 reduced body mass, visceral adiposity, and ectopic lipid deposition without decreasing lean mass. These declines were associated with reductions in ener...
33 CitationsSource
#1Allyson K. Palmer (Mayo Clinic)H-Index: 13
#2James L. Kirkland (Mayo Clinic)H-Index: 59
Adipose tissue dysfunction occurs with aging and has systemic effects, including peripheral insulin resistance, ectopic lipid deposition, and inflammation. Fundamental aging mechanisms, including cellular senescence and progenitor cell dysfunction, occur in adipose tissue with aging and may serve as potential therapeutic targets in age-related disease. In this review, we examine the role of adipose tissue in healthy individuals and explore how aging leads to adipose tissue dysfunction, redistrib...
71 CitationsSource
#1Carolyn M Roos (Mayo Clinic)H-Index: 6
#2Bin Zhang (Mayo Clinic)H-Index: 3
Last. Jordan D. Miller (Mayo Clinic)H-Index: 34
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While reports suggest a single dose of senolytics may improve vasomotor function, the structural and functional impact of long‐term senolytic treatment is unknown. To determine whether long‐term senolytic treatment improves vasomotor function, vascular stiffness, and intimal plaque size and composition in aged or hypercholesterolemic mice with established disease. Senolytic treatment (intermittent treatment with Dasatinib + Quercetin via oral gavage) resulted in significant reductions in senesce...
153 CitationsSource