A5021208221- Genetics, Aging, and Longevity in Model Organisms
- Adipose Tissue and Metabolism
- Physiological and biochemical adaptations
- Birth, Development, and Health
- Circadian rhythm and melatonin
- Dietary Effects on Health
- Mitochondrial Function and Pathology
- Diet and metabolism studies
- Aquaculture Nutrition and Growth
- Muscle metabolism and nutrition
- Regulation of Appetite and Obesity
- Animal Ecology and Behavior Studies
- Exercise and Physiological Responses
- Pancreatic function and diabetes
- Spaceflight effects on biology
- RNA Research and Splicing
- Bat Biology and Ecology Studies
- Parasites and Host Interactions
- Fish Ecology and Management Studies
- Sulfur Compounds in Biology
- Insect Utilization and Effects
- Extracellular vesicles in disease
- Vitamin C and Antioxidants Research
- Diabetes and associated disorders
- RNA modifications and cancer
University of Glasgow
2015-2024
University of Aberdeen
2004-2014
University College London
2005-2014
MRC Unit for Lifelong Health and Ageing
2014
Oxford Centre for Diabetes, Endocrinology and Metabolism
2009
Diabetes Australia
2008
UCL Australia
2005-2007
University of Florida
2003-2005
European Bioinformatics Institute
2005
Durham University
2005
Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component nutrient-responsive mTOR (mammalian target rapamycin) signaling pathway, led to increased resistance age-related pathologies, such as bone, immune, motor dysfunction loss insulin sensitivity. Deletion S6K1 induced gene expression patterns similar those seen CR or with...
Summary Two theories of how energy metabolism should be associated with longevity, both mediated via free‐radical production, make completely contrary predictions. The ‘rate living‐free‐radical theory’ ( Pearl, 1928 ; Harman, 1956 Sohal, 2002 ) suggests a negative association, the ‘uncoupling to survive’ hypothesis Brand, 2000 correlation positive. Existing empirical data on this issue is contradictory and extremely confused Rubner, 1908 Yan & Ragland 1975 Daan et al ., 1996 Wolf...
Recent evidence suggests that alterations in insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) can increase mammalian life span. For example, several mouse mutants, impairment of the hormone (GH)/IGF1 axis increases span and also insulin sensitivity. However, intracellular route to altered aging remains unclear. We therefore measured mice lacking either receptor substrate (IRS) or 2, major effectors IIS receptors. Our provisional results indicate female Irs1-/- are long-lived....
Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding hormones and nutrients in the regulation of energy homeostasis. However, precise neuronal populations cellular mechanisms involved are unclear. The effects long-term manipulation hypothalamic AMPK on balance also unknown. To directly address such issues, we generated POMCα2KO AgRPα2KO mice lacking AMPKα2 proopiomelanocortin– (POMC-) agouti-related protein–expressing...
Recent work on a small European cave salamander (Proteus anguinus) has revealed that it exceptional longevity, yet appears to have unexceptional defences against oxidative damage. This paper comes at the end of string other studies are calling into question free-radical damage theory ageing. rose prominence in 1990s as dominant for why we age and die. Despite substantial correlative evidence support it, last five years raised doubts over its importance. In particular, these include mice with...
Abstract Life‐history theory concerns the trade‐offs that mold patterns of investment by animals between reproduction, growth, and survival. It is widely recognized physiology plays a role in mediation life‐history trade‐offs, but details remain obscure. As aspects soma influence survival, understanding physiological basis life histories related, not identical, to process aging. One idea from field aging has gained considerable traction area may be mediated free radical production oxidative...
Oxidative metabolism has reactive oxygen species (ROS) as unavoidable by–products, and the damage ROS inflicts on DNA, proteins lipids is considered to be a major agent of senescence. Increasing reproductive effort accelerates senescence, but whether increased at expense protection against oxidative not yet been tested. We manipulated in zebra finches through brood size manipulation measured activity two antioxidant enzymes (superoxide dismutase (SOD) glutathione peroxidase (GPx)) pectoral...
Mitochondria are chronically exposed to reactive oxygen intermediates. As a result, various tissues, including skeletal muscle and heart, characterized by an age-associated increase in oxidant-induced mitochondrial DNA (mtDNA) damage. It has been postulated that these alterations may result decline the content rate of production ATP, which affect tissue function, contribute aging process, lead several disease states. We show with age, ATP decreased ∼50% isolated rat mitochondria from...
Insulin receptor substrate 2 (Irs2) plays complex roles in energy homeostasis. We generated mice lacking Irs2 β cells and a population of hypothalamic neurons (RIPCreIrs2KO), all (NesCreIrs2KO), proopiomelanocortin (POMCCreIrs2KO) to determine the role CNS cell. RIPCreIrs2KO displayed impaired glucose tolerance reduced cell mass. Overt diabetes did not ensue, because escaping Cre-mediated recombination progressively populated islets. NesCreIrs2KO hyperphagia, obesity, increased body length,...
Abstract Background To what extent are the determinants of aging in animal species universal? Insulin/insulin-like growth factor (IGF)-1 signaling (IIS) is an evolutionarily conserved (public) regulator longevity; yet it remains unclear whether genes and biochemical processes through which IIS acts on public or private (that is, lineage specific). address this, we have applied a novel, multi-level cross-species comparative analysis to compare gene expression changes accompanying increased...
PI3K signaling is thought to mediate leptin and insulin action in hypothalamic pro-opiomelanocortin (POMC) agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, through largely unknown mechanisms. We inactivated either p110α or p110β catalytic subunits these neurons demonstrate a dominant role for the latter homeostasis regulation. In POMC inactivation prevented insulin- leptin-stimulated electrophysiological responses. POMCp110β null mice exhibited central resistance,...
A central principle in life-history theory is that reproductive effort negatively affects survival. Costs of reproduction are thought to be physiologically based, but the underlying mechanisms remain poorly understood. Using female North American red squirrels (Tamiasciurus hudsonicus), we test hypothesis energetic investment overwhelms antioxidant protection, leading oxidative damage. In support this found highest levels plasma protein damage occurred during energetically demanding period...
There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over relationship between rate oxygen consumption and generation reactive species (ROS). Production ROS (such as hydrogen peroxide, H2O2) mitochondria primarily inferred indirectly from measurements vitro, which may not reflect actual production living animals. Here, we measured vivo H2O2 content using recently developed MitoB probe that becomes concentrated organisms, where it converted...
Evidence suggests that mitochondrial dysfunction and oxidant production, in association with an accumulation of oxidative damage, contribute to the aging process. Regular physical activity can delay onset morbidity, increase mean lifespan, reduce risk developing several pathological states. No studies have examined age-related changes production stress both subsarcolemmal (SSM) interfibrillar (IFM) mitochondria combination lifelong exercise. Therefore, we investigated whether long-term...
ABSTRACT We investigated the relationship between resting metabolic rate (RMR) and various morphological parameters in non-breeding mice, selected for high low food intake corrected body mass. RMR was measured at 30 °C, mice were subsequently killed dissected into 19 components. High-food-intake had significantly greater masses a elevated compared with low-intake mice. Data pooled across strains indicated that mass, sex strain together explained over 56 % of observed variation RMR. The...
We investigated in vivo the chemotherapeutic anthracycline agents doxorubicin and its ability to activate mitochondrial‐mediated, receptor‐mediated endoplasmic/sarcoplasmic reticulum‐mediated apoptosis transduction pathways cardiac tissue from male female rats. administered a single low dose of (10 mg/kg body weight, i.p.) then isolated mitochondrial cytosolic proteins one four days later heart. Caspase‐3 protein content caspase‐3 activity were significantly increased after day treatment...
Defective insulin secretion in response to glucose is an important component of the β cell dysfunction seen type 2 diabetes. As mitochondrial oxidative phosphorylation plays a key role glucose-stimulated (GSIS), oxygen-sensing pathways may modulate release. The von Hippel–Lindau (VHL) protein controls degradation hypoxia-inducible factor (HIF) coordinate cellular and organismal responses altered oxygenation. To determine this pathway controlling release from pancreatic cells, we generated...