A5085080623- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Telomeres, Telomerase, and Senescence
- Circadian rhythm and melatonin
- Adipose Tissue and Metabolism
- Parkinson's Disease Mechanisms and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Dietary Effects on Health
- Epigenetics and DNA Methylation
- Sirtuins and Resveratrol in Medicine
- Tryptophan and brain disorders
- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Genetics and Neurodevelopmental Disorders
- Cancer, Hypoxia, and Metabolism
- Spaceflight effects on biology
- PI3K/AKT/mTOR signaling in cancer
- Diet and metabolism studies
- DNA Repair Mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Genomics, phytochemicals, and oxidative stress
- Histone Deacetylase Inhibitors Research
- Mesenchymal stem cell research
University of Washington
2015-2024
University of Washington Medical Center
2015-2024
Seattle University
2016-2021
Drexel University
2010-2013
University of Milan
2009
Thomas Jefferson University
2009
Sidney Kimmel Cancer Center
2009
KU Leuven
2008
Aging is the main risk factor for Alzheimer's disease (AD); however, aspects of aging process that predispose brain to development AD are largely unknown. Astrocytes perform a myriad functions in central nervous system maintain homeostasis and support neuronal function. In vitro, human astrocytes highly sensitive oxidative stress trigger senescence program when faced with multiple types stress. order determine whether senescent appear vivo, tissue from aged individuals patients was examined...
The FDA approved drug rapamycin increases lifespan in rodents and delays age-related dysfunction humans. Nevertheless, important questions remain regarding the optimal dose, duration, mechanisms of action context healthy aging. Here we show that 3 months treatment is sufficient to increase life expectancy by up 60% improve measures healthspan middle-aged mice. This transient also associated with a remodeling microbiome, including dramatically increased prevalence segmented filamentous...
Coordinated expression of mitochondrial and nuclear genes is required to maintain proper function. However, the precise mechanisms that ensure this coordination are not well defined. We find signaling from mitochondria nucleus influenced by mammalian target rapamycin (mTOR) activity via changes in autophagy p62/SQSTM1 turnover. Reducing mTOR increases autophagic flux, enhances membrane potential, reduces reactive oxygen species within cell, replicative life span. These effects appear be...
In genetically heterogeneous mice produced by the CByB6F1 x C3D2F1 cross, "non-feminizing" estrogen, 17-α-estradiol (17aE2), extended median male lifespan 19% (p < 0.0001, log-rank test) and 11% = 0.007) when fed at 14.4 ppm starting 16 20 months, respectively. 90th percentile lifespans were 7% 0.004, Wang-Allison 5% 0.17). Body weights reduced about 20% after 17aE2 diets. Four other interventions tested in males females: nicotinamide riboside, candesartan cilexetil, geranylgeranylacetone,...
α-Synuclein is one of the principal toxic triggers Parkinson disease, an age-associated neurodegeneration. Using old yeast as a model α-synuclein expression in post-mitotic cells, we show that toxicity depends on chronological aging and results apoptosis well necrosis. Neither disruption key components unfolded protein response nor deletion proapoptotic players (including caspase <i>YCA1</i>, apoptosis-inducing factor <i>AIF1</i>, or serine protease <i>OMI</i>) did prevent...
Rapamycin extends lifespan and attenuates age-related pathologies in mice when administered through diet at 14 parts per million (PPM). Recently, we reported that daily intraperitoneal injection of rapamycin 8 mg/kg mitochondrial disease symptoms progression the Ndufs4 knockout mouse model Leigh Syndrome. Although is a widely used pharmaceutical agent dosage has not been rigorously examined no dose-response profile established. Given these observations sought to determine if increased doses...
Abstract The effects of two different mitochondrial‐targeted drugs, SS‐31 and NMN, were tested on Old mouse hearts. After treatment with the individually or Combined, heart function was examined by echocardiography. partially reversed an age‐related decline in diastolic while NMN fully deficiency systolic at a higher workload. Metabolomic analysis revealed that both Combined increased nicotinamide 1‐methylnicotinamide levels, indicating greater NAD + turnover, but only resulted significantly...
A reduction in IGF-I signaling has been found to increase lifespan multiple organisms despite the fact that is a trophic factor for many cell types and have protective effects against forms of damage acute settings. The longevity seen response reduced suggests there may be differences between chronic impact signaling. We examined possibility long-term stimulation with negative at cellular level using quiescent human fibroblasts. find fibroblast cells exposed 14 days viability as judged by...
Mitochondrial dysfunction can increase oxidative stress and extend lifespan in Caenorhabditis elegans. Homeostatic mechanisms exist to cope with disruptions mitochondrial function that promote cellular health organismal longevity. Previously, we determined decreased expression of the cytosolic pentose phosphate pathway (PPP) enzyme transaldolase activates unfolded protein response (UPRmt) extends lifespan. Here report (tald-1) deficiency impairs vivo, as evidenced by altered morphology,...
The growth factor proepithelin functions as an important regulator of proliferation and motility. Proepithelin is overexpressed in a great variety cancer cell lines clinical specimens breast, ovarian renal cancer, well glioblastomas. Using recombinant on 5637 transitional carcinoma-derived cells, we have shown previously that plays critical role bladder by promoting motility cells. In this study, used the ONCOMINE database gene microarray analysis tool to analyze expression several studies....
Abstract A panel of new potential Ras ligands was generated by decorating a tricyclic levoglucosenone‐derived scaffold with aromatic moieties. Some members the show in vitro inhibitory activity toward nucleotide exchange process on and are toxic to some human cancer cell lines. magnified image
The inactivation of ribosomal protein S6 kinase 1 (S6K1) recapitulates aspects caloric restriction and mTORC1 inhibition to achieve prolonged longevity in invertebrate mouse models. In addition delaying normative aging, extends the shortened lifespan yeast, fly, models with severe mitochondrial disease. Here we tested whether disruption S6K1 can recapitulate beneficial effects Ndufs4 knockout (NKO) model Leigh Syndrome caused by Complex I deficiency. These NKO mice develop profound...
Aging and obesity are common risk factors for numerous chronic pathologies, the compounding effects of old age increased adiposity pose a serious threat to public health. Starting from assumption that aging may have shared underpinnings, we investigated antiobesogenic potential successful longevity intervention, mTORC1 inhibitor rapamycin. We find rapamycin prevents diet-induced in mice increases activity C/EBP-β LAP, transcription factor regulates metabolic shift lipid catabolism observed...