A5061020688- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Muscle Physiology and Disorders
- Exercise and Physiological Responses
- Circadian rhythm and melatonin
- Biochemical effects in animals
- Redox biology and oxidative stress
- Neuroinflammation and Neurodegeneration Mechanisms
- Muscle metabolism and nutrition
- Liver Disease Diagnosis and Treatment
- Coenzyme Q10 studies and effects
- Dietary Effects on Health
- Metabolism and Genetic Disorders
- Birth, Development, and Health
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Cell death mechanisms and regulation
- Diet and metabolism studies
- Genomics, phytochemicals, and oxidative stress
- Carcinogens and Genotoxicity Assessment
- Heat shock proteins research
- Amyotrophic Lateral Sclerosis Research
- Vitamin C and Antioxidants Research
- Trace Elements in Health
University of Oklahoma Health Sciences Center
2016-2025
Oklahoma City VA Medical Center
2015-2024
Oklahoma City University
2017-2021
Oklahoma State University Oklahoma City
1969-2021
Molecular Biology Consortium
2021
OU Health Stephenson Cancer Center
2020-2021
Veterans Health Administration
2019
OU Health
2016-2018
Star Center
2017-2018
University of Oklahoma
2018
Rapamycin, an inhibitor of mechanistic target rapamycin complex 1 (mTORC1), extends the life spans yeast, flies, and mice. Calorie restriction, which increases span insulin sensitivity, is proposed to function by inhibition mTORC1, yet paradoxically, chronic administration substantially impairs glucose tolerance action. We demonstrate that disrupted a second mTOR complex, mTORC2, in vivo mTORC2 was required for insulin-mediated suppression hepatic gluconeogenesis. Further, decreased mTORC1...
Background Reduced TOR signaling has been shown to significantly increase lifespan in a variety of organisms [1], [2], [3], [4]. It was recently demonstrated that long-term treatment with rapamycin, an inhibitor the mTOR pathway[5], or ablation target p70S6K[6] extends mice, possibly by delaying aging. Whether inhibition pathway would delay prevent age-associated disease such as AD remained be determined. Methodology/Principal Findings We used rapamycin administration and behavioral tools...
Accumulation of amyloid-β (Aβ) and Tau is an invariant feature Alzheimer disease (AD). The upstream role Aβ accumulation in the pathogenesis widely accepted, there strong evidence showing that causes cognitive impairments. However, molecular mechanisms linking to decline remain be elucidated. Here we show buildup increases mammalian target rapamycin (mTOR) signaling, whereas decreasing mTOR signaling reduces levels, thereby highlighting interrelation between Aβ. pathway plays a central...
Mice heterozygous for the Sod2 gene ( +/− mice) have been used to study phenotype of life-long reduced Mn-superoxide dismutase (MnSOD) activity. The mice MnSOD activity (∼50%) in all tissues throughout life. increased oxidative damage as demonstrated by significantly elevated levels 8-oxo-2-deoxyguanosine (8oxodG) nuclear DNA studied. 8oxodG with age and wild-type (WT) mice, at 26 mo age, were higher (from 15% heart over 60% liver) compared WT mice. level was also mitochondrial isolated from...
This study characterizes mitochondria isolated from livers of Sod2 −/+ and +/+ mice. A 50% decrease in manganese superoxide dismutase (MnSOD) activity was observed mice compared withSod2 mice, with no change the activities either glutathione peroxidase or copper/zinc dismutase. However, level total 30% less liver The reduction MnSOD correlated to an increase oxidative damage mitochondria: decreased Fe-S proteins (aconitase NADH oxidoreductase), increased carbonyl groups proteins, levels...
The widely accepted oxidative stress theory of aging postulates that results from accumulation damage. Surprisingly, data the longest-living rodent known, naked mole-rats [MRs; mass 35 g; maximum lifespan (MLSP) > 28.3 years], when compared with mice (MLSP 3.5 years) exhibit higher levels lipid peroxidation, protein carbonylation, and DNA damage even at a young age. We hypothesize age-related changes in structural stability, oxidation, degradation are abrogated over MR. performed...
Previous studies have shown that inducing autophagy ameliorates early cognitive deficits associated with the build-up of soluble amyloid-β (Aβ). However, effects on plaques and tangles are yet to be determined. While Aβ tau represent toxic species in Alzheimer's disease (AD) pathogenesis, there is well documented evidence also detrimental normal brain function. Thus, it critical assess an animal model established tangles. Here we show rapamycin, when given prophylactically 2-month-old...
Reactive oxygen species (ROS), especially mitochondrial ROS, are postulated to play a significant role in muscle atrophy. We report dramatic increase ROS generation three conditions associated with atrophy: aging, mice lacking CuZn-SOD (Sod1(-/-)), and the neurodegenerative disease, amyotrophic lateral sclerosis (ALS). mitochondria is nearly threefold higher 28- 32-mo-old than 10-mo-old 30% loss gastrocnemius mass. In Sod1(-/-) mice, production increased >100% 20-mo compared 5-mo-old along...
The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested parallel at three sites, and all results are published. We report the effects of lifelong treatment mice with four not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) metformin – latter without rapamycin, two drugs examined: 17-α-estradiol nordihydroguaiaretic (NDGA), doses greater less...
Oxidative stress has been implicated in the etiology of age-related muscle loss (sarcopenia). However, underlying mechanisms by which oxidative contributes to sarcopenia have not thoroughly investigated. To directly examine role chronic vivo, we used a mouse model that lacks antioxidant enzyme CuZnSOD (Sod1). Sod1(-/-) mice are characterized high levels damage and an acceleration sarcopenia. In present study, demonstrate atrophy is accompanied progressive decline mitochondrial bioenergetic...
Target of rapamycin inhibition by feeding has previously been shown to extend life in genetically heterogeneous mice. To examine whether it similarly affected mouse health, we fed encapsulated or a control diet C57BL/6Nia mice both sexes starting at 19 months age. We performed range health assessments 6 and 12 later. Rapamycin significantly reduced mTOR activity most but not all tissues. It also total resting metabolic rate during the light (inactive) phase light:dark cycle females only had...
Inflammaging, characterized by an increase in low-grade chronic inflammation with age, is a hallmark of aging and strongly associated various age-related diseases, including liver disease (CLD) hepatocellular carcinoma (HCC). Because necroptosis cell death pathway that induces through the release DAMPs, we tested hypothesis age-associated contributes to liver. Phosphorylation MLKL oligomers, markers necroptosis, as well phosphorylation RIPK3 RIPK1 were significantly upregulated livers old...
Because heat shock proteins have been shown to play a critical role in protecting cells from hyperthermia and other types of physiological stresses, it was interest determine what effect age caloric restriction on the ability regulate expression protein 70 (hsp70), most prominent evolutionarily conserved proteins. Caloric is only experimental manipulation known retard aging increase survival mammals. The hepatocytes isolated young/adult (4- 7-month-old) old (22- 28-month-old) male Fischer...