A5040077574- Genetics, Aging, and Longevity in Model Organisms
- FOXO transcription factor regulation
- Circadian rhythm and melatonin
- Neurobiology and Insect Physiology Research
- Telomeres, Telomerase, and Senescence
- Health, Environment, Cognitive Aging
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- Plant Molecular Biology Research
- Genomics, phytochemicals, and oxidative stress
- Hormonal Regulation and Hypertension
- Nuclear Receptors and Signaling
- Radical Photochemical Reactions
- Dietary Effects on Health
- Physiological and biochemical adaptations
- Catalytic C–H Functionalization Methods
- Developmental Biology and Gene Regulation
- Cell Adhesion Molecules Research
- Heat shock proteins research
- Genetics and Neurodevelopmental Disorders
- Neuropeptides and Animal Physiology
- Pharmacological Effects and Assays
- Metabolism, Diabetes, and Cancer
- Insurance, Mortality, Demography, Risk Management
- Protein Tyrosine Phosphatases
Aston University
2017-2025
University of Warwick
2025
University College London
2006-2016
Max Planck Institute for Biology of Ageing
2015-2016
Robert Bosch (Germany)
2016
MRC Unit for Lifelong Health and Ageing
2010-2013
Max Planck Society
2008-2010
King's College London
2006-2007
Princess Anne Hospital
2000
University of Southampton
2000
The target of rapamycin (TOR) pathway is a major nutrient-sensing that, when genetically downregulated, increases life span in evolutionarily diverse organisms including mammals. central component this pathway, TOR kinase, the inhibitory drug rapamycin, highly specific and well-described approved for human use. We show here that feeding to adult Drosophila produces extension seen some mutants. Increase by was associated with increased resistance both starvation paraquat. Analysis underlying...
The quest to extend healthspan via pharmacological means is becoming increasingly urgent, both from a health and economic perspective. Here we show that lithium, drug approved for human use, promotes longevity healthspan. We demonstrate lithium extends lifespan in female male Drosophila, when administered throughout adulthood or only later life. life-extending mechanism involves the inhibition of glycogen synthase kinase-3 (GSK-3) activation transcription factor nuclear erythroid 2-related...
The insulin/insulin-like growth factor-like signaling (IIS) pathway in metazoans has evolutionarily conserved roles control, metabolic homeostasis, stress responses, reproduction, and lifespan. Genetic manipulations that reduce IIS the nematode worm Caenorhabditis elegans, fruit fly Drosophila melanogaster, mouse have been shown not only to produce substantial increases lifespan but also ameliorate several age-related diseases. In C. multitude of phenotypes produced by reduction are all...
The insulin/IGF-like signalling (IIS) pathway has diverse functions in all multicellular organisms, including determination of lifespan. seven insulin-like peptides (DILPs) Drosophila are expressed a stage- and tissue-specific manner. Partial ablation the median neurosecretory cells (mNSCs) brain, which produce three DILPs, extends lifespan, reduces fecundity, alters lipid carbohydrate metabolism increases oxidative stress resistance. To determine if reduced expression DILPs is causal these...
The biguanide drug, metformin, commonly used to treat type-2 diabetes, has been shown extend lifespan and reduce fecundity in C. elegans through a dietary restriction-like mechanism via the AMP-activated protein kinase (AMPK) AMPK-activating kinase, LKB1. We have investigated whether longevity-promoting effects of metformin are evolutionarily conserved using fruit fly, Drosophila melanogaster. show here that while feeding adult resulted robust activation AMPK reduced lipid stores, it did not...
Summary Dietary restriction extends lifespan in diverse organisms, but the gene regulatory mechanisms and tissues mediating increased survival are still unclear. Studies worms flies have revealed a number of candidate mechanisms, including target rapamycin insulin/IGF‐like signalling (IIS) pathways suggested specific role for nervous system response. A pair sensory neurons Caenorhabditis elegans has been found to specifically mediate DR extension, neuronal focus Drosophila not yet...
Comprehensive disease classification and staging is required to address unmet needs of aging populations
Drosophila Lnk is the single ancestral orthologue of a highly conserved family structurally-related intracellular adaptor proteins, SH2B proteins. As adaptors, they lack catalytic activity but contain several protein–protein interaction domains, thus playing critical role in signal transduction from receptor tyrosine kinases to form protein networks. Physiological studies function mammals have produced conflicting data. However, recent study has shown that an important regulator...
Drosophila melanogaster and Caenorhabditis elegans each carry a single representative of the Forkhead box O (FoxO) family transcription factors, dFOXO DAF-16, respectively. Both are required for lifespan extension by reduced insulin/Igf signaling, their activation in key tissues can extend lifespan. Aging these may limit Alternatively, FoxOs promote longevity cell nonautonomously signaling to themselves (FoxO FoxO) or other factors other) distal tissues. Here, we show that DAF-16 gut/fat...
Invertebrate models have been instrumental in advancing our understanding of the molecular mechanisms ageing. The isolation single gene mutations that both extend lifespan and improve age-related health identified potential targets for therapeutic intervention to alleviate morbidity. Here, we find genetic loss function G protein-coupled metabotropic glutamate receptor (DmGluRA) Drosophila extends female flies. This longevity phenotype was accompanied by lower basal levels oxidative stress...
Mating rate is a major determinant of female lifespan and fitness, predicted to optimize at an intermediate level, beyond which superfluous matings are costly. In Drosophila melanogaster , nutrition key regulator mating but the underlying mechanism unknown. The evolutionarily conserved insulin/insulin-like growth factor-like signalling (IIS) pathway responsive nutrition, regulates development, metabolism, stress resistance, fecundity lifespan. Here we show that inhibition IIS, by ablation...
RNA interference (RNAi) provides an important tool for gene function discovery. It has been widely exploited in Caenorhabditis elegans ageing research because it does not appear to have any non-specific effects on ageing-related traits that model organism. We show here ubiquitous, adult-onset activation of the RNAi machinery, achieved by expressing a double stranded targeting GFP or lacZ degradation, increasing expression Dicer substantially reduces lifespan Drosophila melanogaster....
Asymmetric cell divisions generate fate diversity during both invertebrate and vertebrate development. Drosophila neural progenitors or neuroblasts (NBs) each divide asymmetrically to produce a larger neuroblast smaller ganglion mother (GMC). The asymmetric localisation of determinants their adapter proteins the cortex mitosis facilitates preferential segregation GMC upon cytokinesis. In this study we report novel role for anaphase-promoting complex/cyclosome (APC/C) process. Attenuation...
Over recent decades, increased longevity has not been paralleled by extended health span, resulting in more years spent with multiple diseases older age. As such, interventions to improve span are urgently required. Zoledronate (Zol) is a nitrogen-containing bisphosphonate, which inhibits the farnesyl pyrophosphate synthase enzyme, central mevalonate pathway. It already used clinically prevent fractures osteoporotic patients, who have reported derive unexpected and unexplained survival...
Abstract Background The asymmetric segregation of determinants during cell division is a fundamental mechanism for generating fate diversity development. In Drosophila , neural precursors (neuroblasts) divide in stem cell-like manner larger apical neuroblast and smaller basal ganglion mother cell. determinant Prospero its adapter protein Miranda are asymmetrically localized to the cortex dividing segregated into GMC upon cytokinesis. Previous screens identify components machinery have...
Human ovarian granulosa cells were cultured on a basement membrane preparation (Matrigel) to investigate the role of extracellular matrix components in cell cluster formation. Time‐lapse videomicroscopy these cultures revealed rapid aggregation which was initiated during first 2–4 h culture so that by 8 most incorporated into clusters. Further amalgamation then occurred with transfer along ‘bridges’ between combining The clustering process, complete about 24 h, accompanied reorganisation...