A5085337287- Genetics, Aging, and Longevity in Model Organisms
- Autophagy in Disease and Therapy
- Lysosomal Storage Disorders Research
- Metabolism and Genetic Disorders
- Nutrition, Genetics, and Disease
- Porphyrin Metabolism and Disorders
- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Circadian rhythm and melatonin
- Neurological diseases and metabolism
- FOXO transcription factor regulation
- Parkinson's Disease Mechanisms and Treatments
- Stress Responses and Cortisol
- Hormonal Regulation and Hypertension
- Endoplasmic Reticulum Stress and Disease
- Cholinesterase and Neurodegenerative Diseases
- Spaceflight effects on biology
- Mosquito-borne diseases and control
- Genomics, phytochemicals, and oxidative stress
- Cellular transport and secretion
- Nuclear Receptors and Signaling
- Health Systems, Economic Evaluations, Quality of Life
- Frailty in Older Adults
- Adipokines, Inflammation, and Metabolic Diseases
- Lipid metabolism and biosynthesis
Harvard University
2016-2023
Joslin Diabetes Center
2016-2023
Harvard Stem Cell Institute
2016-2023
University College London
2011-2020
MRC Unit for Lifelong Health and Ageing
2015-2020
Max Planck Institute for Biology of Ageing
2014-2020
National Hospital for Neurology and Neurosurgery
2012-2016
Autonomous University of Yucatán
2007-2010
Institute for Social Security and Services for State Workers
2009
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 PLA2G6 gene encodes a group VIA calcium-independent phospholipase A2 beta enzyme that selectively hydrolyses glycerophospholipids to release free fatty acids. Mutations in have been associated with disorders such as infantile neuroaxonal dystrophy, neurodegeneration brain iron accumulation type II and Karak syndrome. More recently, was identified the causative subgroup of patients autosomal recessive early-onset dystonia-parkinsonism. Neuropathological examination revealed widespread...
Summary and comment on a recent Nature paper entitled ‘A PGC1-α-dependent myokine that drives brown-fat-like development of white fat thermogenesis’ (Boström et al., 2012).
Glucocerebrosidase ( GBA1 ) mutations are associated with Gaucher disease (GD), an autosomal recessive disorder caused by functional deficiency of glucocerebrosidase (GBA), a lysosomal enzyme that hydrolyzes glucosylceramide to ceramide and glucose. Neuronopathic forms GD can be rapid neurological decline (Type II) or manifest as chronic form III) wide spectrum signs. Furthermore, there is now well-established link between Parkinson's (PD), heterozygote in considered the commonest genetic...
Nrf2, a transcriptional activator of cell protection genes, is an attractive therapeutic target for the prevention neurodegenerative diseases, including Alzheimer's disease (AD). Current Nrf2 activators, however, may exert toxicity and pathway over-activation can induce detrimental effects. An understanding mechanisms mediating inhibition in conditions therefore direct design drugs targeted these diseases with minimal side-effects. Our study provides first vivo evidence that specific Keap1,...
The greatest risk factor for Alzheimer's disease (AD) is age, and changes in the ageing nervous system are likely contributors to AD pathology. Amyloid beta (Aβ) accumulation, which occurs as a result of amyloidogenic processing amyloid precursor protein (APP), thought initiate pathogenesis AD, eventually leading neuronal cell death. Previously, we developed an adult-onset Drosophila model AD. Mutant Aβ42 accumulation led increased mortality dysfunction adult flies. Furthermore, showed that...
Increasing life expectancy is causing the prevalence of age-related diseases to rise, and there an urgent need for new strategies improve health at older ages. Reduced activity insulin/insulin-like growth factor signaling (IIS) mechanistic target rapamycin (mTOR) nutrient-sensing network can extend lifespan during aging in diverse organisms. However, extensive feedback this adverse side effects inhibition imply that simultaneous targeting specific effectors may most effectively combat aging....
Although excessive lipid accumulation is a hallmark of obesity-related pathologies, some lipids are beneficial. Oleic acid (OA), the most abundant monounsaturated fatty (FA), promotes health and longevity. Here, we show that OA benefits Caenorhabditis elegans by activating endoplasmic reticulum (ER)-resident transcription factor SKN-1A (Nrf1/NFE2L1) in homeostasis response. SKN-1A/Nrf1 cleared from ER ER-associated degradation (ERAD) machinery stabilized when proteasome activity low...
Increased cellular degradation by autophagy is a feature of many interventions that delay ageing. We report here increased necessary for reduced insulin-like signalling (IIS) to extend lifespan in Drosophila and sufficient on its own increase lifespan. first established the well-characterised extension associated with deletion insulin receptor substrate chico was completely abrogated downregulation essential gene Atg5 . next directly induced over-expressing major kinase Atg1 found mild...
The groundbreaking discovery that lower levels of insulin/IGF-1 signaling (IIS) can induce lifespan extension was reported 24 years ago in the nematode <i>Caenorhabditis elegans</i>. In this organism, mutations receptor gene <i>daf-2</i> or other genes pathway double lifespan. Subsequent work has revealed reduced IIS (rIIS) extends across diverse species, possibly including humans. <i>C. elegans</i>, also regulates development into diapause state known as...
Mutations in the GBA1 gene cause lysosomal storage disorder Gaucher disease (GD) and are greatest known genetic risk factors for Parkinson’s (PD). Communication between gut brain immune dysregulation increasingly being implicated neurodegenerative disorders such as PD. Here, we show that flies lacking Gba1b gene, main fly orthologue of , display widespread NF -k B signalling activation, including inflammation, glial activation. We also demonstrate intestinal autophagic defects, dysfunction,...
Worldwide, diabetes mellitus and depression are among the most prevalent diseases in their respective fields, metabolism psychiatry. However, there is evidence that patients with at increased risk of developing depression, although a bidirectional relationship might also exist.To present comprehensive review clinical, epidemiological, psychosocial, emotional, neurobiological basis relation between depression.Epidemiological studies indicate not only an augmented diabetic patients, but this...
The PLA2G6 gene encodes a group VIA calcium independent phospholipase A2 (iPLA2β), which hydrolyses glycerophospholipids to release fatty acids and lysophospholipids. Mutations in are associated with number of neurodegenerative disorders including neurodegeneration brain iron accumulation (NBIA), infantile neuroaxonal dystrophy (INAD), dystonia parkinsonism, collectively known as PLA2G6-associated (PLAN). Recently Kinghorn et al. demonstrated Drosophila mutant fibroblasts that loss normal...
Around the world, individuals are living longer, but an increased average lifespan does not always equate to healthspan. With advancing age, prevalence of ageing-related diseases can have a significant impact on health status, functional capacity, and quality life. It is therefore vital develop comprehensive classification staging systems for pathologies, syndromes. This will allow societies better identify, quantify, understand, meet healthcare, workforce, wellbeing, socioeconomic needs...
Abstract Although excessive lipid accumulation is a hallmark of obesity-related pathologies, some lipids are beneficial. Oleic acid (OA), the most abundant monounsaturated fatty (FA), promotes health and longevity. Here we show that OA benefits C. elegans by activating endoplasmic reticulum (ER)-resident transcription factor SKN-1A (Nrf1/NFE2L1) in homeostasis response. SKN-1A/Nrf1 cleared from ER ER-associated degradation (ERAD) machinery stabilized when proteasome activity low, canonically...