A5026885261- Adipose Tissue and Metabolism
- Birth, Development, and Health
- Growth Hormone and Insulin-like Growth Factors
- Diet and metabolism studies
- Telomeres, Telomerase, and Senescence
- Circadian rhythm and melatonin
- Stress Responses and Cortisol
- Adipokines, Inflammation, and Metabolic Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Neurological Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
- Metabolomics and Mass Spectrometry Studies
- Dietary Effects on Health
- Neuroendocrine regulation and behavior
- PI3K/AKT/mTOR signaling in cancer
- Lipid metabolism and biosynthesis
- Retinoids in leukemia and cellular processes
- Neuropeptides and Animal Physiology
- Metabolism, Diabetes, and Cancer
- Medicinal Plants and Neuroprotection
- Childhood Cancer Survivors' Quality of Life
- Computational Drug Discovery Methods
Southern Illinois University School of Medicine
2016-2024
Neurosciences Institute
2022-2024
University of Alabama at Birmingham
2016
SUNY Upstate Medical University
1959
Senolytic treatment in aged mice clears senescent cell burden leading to functional improvements. However, less is known regarding the effects of these compounds when administered prior significant accumulation. From 4-13 months age, C57BL/6 male and female received monthly oral dosing either 100 mg/kg Fisetin or a 5 Dasatinib (D) plus 50 Quercetin (Q) cocktail. During treatment, several aspects healthy aging were assayed including glucose metabolism using an insulin tolerance test,...
The hearts of young anesthetized goats, pigs and puppies were exposed for electrical stimulation recording. Bipolar electrodes attached to the right atrium ventricle. sinus node was crushed. heart driven by stimuli applied atrial appendage. At intervals, one or two ‘premature’ responses induced assess time relations A-V transmission. In all experiments with goats earliest possible premature responses, on transmission ventricle, yielded electrograms bizarre configuration. some preparations...
Life-long lack of growth hormone (GH) action can produce remarkable extension longevity in mice. Here we report that GH treatment limited to a few weeks during development influences the lifespan long-lived Ames dwarf and normal littermate control mice genotype sex-specific manner. Studies separate cohort show this short period exposure early produces persistent phenotypic, metabolic molecular changes are evident late adult life. These effects may represent mechanisms responsible for reduced...
Ames dwarf mice (Prop1df/df) are long-lived due to a loss of function mutation, resulting in deficiency GH, TSH, and prolactin. Along with marked extension longevity, have improved energy metabolism as measured by an increase their oxygen consumption heat production, well decrease respiratory quotient. alterations metabolism, lower core body temperature. Moreover, functionally altered epididymal white adipose tissue (WAT) that improves, rather than impairs, insulin sensitivity shift from...
Abstract Senescent cells accumulate throughout the body and brain contributing to unhealthy aging Alzheimer’s disease (AD). The APP NL−F/NL−F amyloidogenic AD mouse model exhibits increased markers of senescent senescence-associated secretory phenotype (SASP) in visceral white adipose tissue hippocampus before plaque accumulation cognitive decline. We hypothesized that senolytic intervention would alleviate cellular senescence thereby improving spatial memory mice. Thus, 4-month-old male...
Significance In various animal species, including mammals, longevity can be extended by rapamycin, an inhibitor of mTOR (mechanistic target rapamycin). acts through two complexes: mTORC1 and mTORC2. Antiaging effects rapamycin are mediated suppression mTORC1, while the role mTORC2 in aging remains to elucidated. Here, we report that plays a positive regulating via maintenance, or enhancement, whole-body homeostasis. When mTORC2-mediated homeostasis was disrupted remarkably long-lived GHR-KO...
Recent studies have demonstrated the remarkable potential of early life intervention strategies at influencing course postnatal development, thereby offering exciting possibilities for enhancing longevity and improving overall health. Metformin (MF), an FDA-approved medication type II diabetes mellitus, has recently gained attention its promising anti-aging properties, acting as a calorie restriction mimetic, delaying precocious puberty. Additionally, trodusquemine (MSI-1436),...
Aging is the greatest risk factor for most chronic diseases. The somatotropic axis one of conserved biological pathways that regulates aging across species. 17α-Estradiol (17α-E2), a diastereomer 17β-estradiol (17β-E2), was recently found to elicit health benefits, including improved insulin sensitivity and extend longevity exclusively in male mice. Given 17β-E2 known modulate signaling females through actions pituitary liver, we hypothesized 17α-E2 may be modulating males, thereby...
Background It is well established that glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies indicate glutamate dynamics shift with Alzheimer's disease (AD) progression, contributing to negative cognitive outcomes. Objective In this study, we characterized hippocampal signaling age progression a knock-in mouse model of AD (APP NL-F/NL--F ). Methods At 2–4 18+ months old, male female APP NL/NL , NL-F/NL-F C57BL/6 mice underwent assessment using...
Abstract Growth hormone receptor knockout (GHRKO) mice are remarkably long‐lived and have improved glucose homeostasis along with altered energy metabolism which manifests through decreased respiratory quotient (RQ) increased oxygen consumption (VO 2 ). Short‐term exposure of these animals to environmental temperature (eT) at 30°C can normalize their VO RQ. We hypothesized that heat loss in the diminutive GHRKO housed 23°C consequent metabolic adjustments meet demand for thermogenesis may...
Prior research supports a strong link between Alzheimer's disease (AD) and metabolic dysfunction that involves multi-directional interaction glucose, glutamatergic homeostasis, amyloid pathology. Elevated soluble amyloid-β (Aβ) is an early biomarker for AD-associated cognitive decline contributes to concurrent dyshomeostasis in humans male transgenic AD mice. Yet, it remains unclear how primary time-sensitive targeting of hippocampal activity may impact glucose regulation amyloidogenic mouse...
Ames dwarf mice are exceptionally long-lived due to a Prop1 loss of function mutation resulting in deficiency growth hormone, thyroid-stimulating hormone and prolactin. Deficiency leads greatly reduced levels circulating thyroid hormones insulin-like factor 1, as well reduction insulin secretion. Early life replacement therapy significantly shortens their longevity, while early thyroxine (T4) does not. Possible mechanisms by which longevity include deleterious effects on glucose homeostasis...
Ames dwarf (Prop1df) mice possess a loss-of-function mutation that results in deficiency of growth hormone, prolactin, and thyroid-stimulating as well exceptional longevity. Work other laboratories suggests increased respiration lipid utilization are important for maximizing mammalian Interestingly, these phenotypes observed mice. We recently demonstrated have hyperactive brown adipose tissue (BAT), hypothesized this may part be due to their surface mass ratio leading heat loss an demand...
Abstract A thermoregulatory decline occurs with age due to changes in muscle mass, vasoconstriction, and metabolism that lowers core body temperature (Tc). Although lower Tc is a biomarker of successful aging, we have previously shown this worsens cognitive performance the APP/PS1 mouse model Alzheimer’s disease (AD) [1]. We hypothesized elevating thermotherapy would improve cognition mice. From 6-12 months age, male female C57BL/6 mice were chronically housed at 23 or 30°C. At 12 assayed...
Aging | doi:10.18632/aging.206156. Samuel A. McFadden, Mackenzie R. Peck, Lindsey N. Sime, MaKayla F. Cox, Erol D. Ikiz, Caleigh Findley, Kathleen Quinn, Yimin Fang, Andrzej Bartke, Erin Hascup, Kevin Hascup
Metabolic dysfunction increases with age and is a contributing factor to Alzheimer's disease (AD) development. We have previously observed impaired insulin sensitivity glucose homeostasis in the APP/PS1 model of AD. To improve these parameters, we chronically exposed male female mice mild hypothermic environmental temperature (eT), which positively modulates metabolism. Although eT normalized sensitivity, tolerance was still both sexes AD mice. increased plasma glucagon B-cell activating...
Abstract Background Glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies support a dynamic shift excitatory signaling with Alzheimer’s disease (AD) progression, contributing to negative cognitive outcomes. The majority of previous have relied heavily on male physiology when determining these alterations AD mouse models. Here, we examine sex differences cognition using the APP NL‐F model AD. Method Male female control C57BL/6 mice underwent...
Abstract Background It is well established that glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies indicate glutamate dynamics shift with Alzheimer’s disease (AD) progression, contributing to negative cognitive outcomes. Objective In this study, we characterized hippocampal signaling age progression a knock-in mouse model of AD (APP NL-F/NL-F ). Methods At 2-4 18+ months old, male female APP NL/NL , C57BL/6 mice underwent assessment using Morris...
Abstract Senolytic treatment in aged mice clears senescent cell burden leading to functional improvements. However, less is known regarding the effects of these compounds when administered prior significant accumulation. From 4-13 months age, C57BL/6 male and female received monthly oral dosing either 100 mg/kg Fisetin or a 5 Dasatinib (D) plus 50 Quercetin (Q) cocktail. During treatment, several aspects healthy aging were assayed including glucose metabolism using an insulin tolerance test,...
Growth hormone receptor knockout (GHRKO) mice are smaller, long living, and have an increased metabolic rate compared with normal (N) littermates. However, it is known that thermoneutral conditions (30-32°C) elicit adaptations in mice, increasing the rate. Therefore, we hypothesized environmental temperature would affect expression profile of different adipose tissue depots GHRKO mice. For this, N (n = 12) 11) male were maintained at 23 or 30°C from weaning until 11 months age. RNA...