Endocannabinoids, FOXO and the metabolic syndrome: redox, function and tipping point--the view from two systems

The endocannabinoid system (ECS) was only 'discovered' in the 1990s. Since then, many new ligands have been identified, as well as many new intracellular targets--ranging from the PPARs, to mitochondria, to lipid rafts. It was thought that blocking the CB-1 receptor might reverse obesity and the metabolic syndrome. This was based on the idea that the ECS was dysfunctional in these conditions. This has met with limited success. The reason may be that the ECS is a homeostatic system, which integrates energy seeking and storage behaviour with resistance to oxidative stress. It could be viewed as having thrifty actions. Thriftiness is an innate property of life, which is programmed to a set point by both environment and genetics, resulting in an epigenotype perfectly adapted to its environment. This thrifty set point can be modulated by hormetic stimuli, such as exercise, cold and plant micronutrients. We have proposed that the physiological and protective insulin resistance that underlies thriftiness encapsulates something called 'redox thriftiness', whereby insulin resistance is determined by the ability to resist oxidative stress. Modern man has removed most hormetic stimuli and replaced them with a calorific sedentary lifestyle, leading to increased risk of metabolic inflexibility. We suggest that there is a tipping point where lipotoxicity in adipose and hepatic cells induces mild inflammation, which switches thrifty insulin resistance to inflammation-driven insulin resistance. To understand this, we propose that the metabolic syndrome could be seen from the viewpoint of the ECS, the mitochondrion and the FOXO group of transcription factors. FOXO has many thrifty actions, including increasing insulin resistance and appetite, suppressing oxidative stress and shifting the organism towards using fatty acids. In concert with factors such as PGC-1, they also modify mitochondrial function and biogenesis. Hence, the ECS and FOXO may interact at many points; one of which may be via intracellular redox signalling. As cannabinoids have been shown to modulate reactive oxygen species production, it is possible that they can upregulate anti-oxidant defences. This suggests they may have an 'endohormetic' signalling function. The tipping point into the metabolic syndrome may be the result of a chronic lack of hormetic stimuli (in particular, physical activity), and thus, stimulus for PGC-1, with a resultant reduction in mitochondrial function and a reduced lipid capacitance. This, in the context of a positive calorie environment, will result in increased visceral adipose tissue volume, abnormal ectopic fat content and systemic inflammation. This would worsen the inflammatory-driven pathological insulin resistance and inability to deal with lipids. The resultant oxidative stress may therefore drive a compensatory anti-oxidative response epitomised by the ECS and FOXO. Thus, although blocking the ECS (e.g. via rimonabant) may induce temporary weight loss, it may compromise long-term stress resistance. Clues about how to modulate the system more safely are emerging from observations that some polyphenols, such as resveratrol and possibly, some phytocannabinoids, can modulate mitochondrial function and might improve resistance to a modern lifestyle.

Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

The metabolic syndrome may have its origins in thriftiness, insulin resistance and one of the most ancient of all signalling systems, redox. Thriftiness results from an evolutionarily-driven propensity to minimise energy expenditure. This has to be balanced with the need to resist the oxidative stress from cellular signalling and pathogen resistance, giving rise to something we call 'redox-thriftiness'. This is based on the notion that mitochondria may be able to both amplify membrane-derived redox growth signals as well as negatively regulate them, resulting in an increased ATP/ROS ratio. We suggest that 'redox-thriftiness' leads to insulin resistance, which has the effect of both protecting the individual cell from excessive growth/inflammatory stress, while ensuring energy is channelled to the brain, the immune system, and for storage. We also suggest that fine tuning of redox-thriftiness is achieved by hormetic (mild stress) signals that stimulate mitochondrial biogenesis and resistance to oxidative stress, which improves metabolic flexibility. However, in a non-hormetic environment with excessive calories, the protective nature of this system may lead to escalating insulin resistance and rising oxidative stress due to metabolic inflexibility and mitochondrial overload. Thus, the mitochondrially-associated resistance to oxidative stress (and metabolic flexibility) may determine insulin resistance. Genetically and environmentally determined mitochondrial function may define a 'tipping point' where protective insulin resistance tips over to inflammatory insulin resistance. Many hormetic factors may induce mild mitochondrial stress and biogenesis, including exercise, fasting, temperature extremes, unsaturated fats, polyphenols, alcohol, and even metformin and statins. Without hormesis, a proposed redox-thriftiness tipping point might lead to a feed forward insulin resistance cycle in the presence of excess calories. We therefore suggest that as oxidative stress determines functional longevity, a rather more descriptive term for the metabolic syndrome is the 'lifestyle-induced metabolic inflexibility and accelerated ageing syndrome'. Ultimately, thriftiness is good for us as long as we have hormetic stimuli; unfortunately, mankind is attempting to remove all hormetic (stressful) stimuli from his environment.

Obesity, diabetes and longevity in the Gulf: is there a Gulf Metabolic Syndrome?

The Gulf is experiencing a pandemic of lifestyle-induced obesity and type 2 diabetes mellitus (T2DM), with rates exceeding 50 and 30%, respectively. It is likely that T2DM represents the tip of a very large metabolic syndrome iceberg, which precedes T2DM by many years and is associated with abnormal/ectopic fat distribution, pathological systemic oxidative stress and inflammation. However, the definitions are still evolving with the role of different fat depots being critical. Hormetic stimuli, which include exercise, calorie restriction, temperature extremes, dehydration and even some dietary components (such as plant polyphenols), may well modulate fat deposition. All induce physiological levels of oxidative stress, which results in mitochondrial biogenesis and increased anti-oxidant capacity, improving metabolic flexibility and the ability to deal with lipids. We propose that the Gulf Metabolic Syndrome results from an unusually rapid loss of hormetic stimuli within an epigenetically important time frame of 2-3 generations. Epigenetics indicates that thriftiness can be programmed by the environment and passed down through several generations. Thus this loss of hormesis can result in continuation of metabolic inflexibility, with mothers exposing the foetus to a milieu that perpetuates a stressed epigenotype. As the metabolic syndrome increases oxidative stress and reduces life expectancy, a better descriptor may therefore be the Lifestyle-Induced Metabolic Inflexibility and accelerated AGEing syndrome – LIMIT-AGE. As life expectancy in the Gulf begins to fall, with perhaps a third of this life being unhealthy – including premature loss of sexual function, it is vital to detect evidence of this condition as early in life as possible. One effective way to do this is by detecting evidence of metabolic inflexibility by studying body fat content and distribution by magnetic resonance (MR). The Gulf Metabolic Syndrome thus represents an accelerated form of the metabolic syndrome induced by the unprecedented rapidity of lifestyle change in the region, the stress of which is being passed from generation to generation and may be accumulative. The fundamental cause is probably due to a rapid increase in countrywide wealth. This has benefited most socioeconomic groups, resulting in the development of an obesogenic environment as the result of the rapid adoption of Western labour saving and stress relieving devices (e.g. cars and air conditioning), as well as the associated high calorie diet.

Hydrophilic interaction chromatography–mass spectrometry for anionic metabolic profiling of urine from antibiotic-treated rats

Hydrophilic interaction chromatography–mass spectrometry (HILIC–MS) was used for anionic metabolic profiling of urine from antibiotic-treated rats to study microbial–host co-metabolism. Rats were treated with the antibiotics penicillin G and streptomycin sulfate for four or eight days and compared to a control group. Urine samples were collected at day zero, four and eight, and analyzed by HILIC–MS. Multivariate data analysis was applied to the urinary metabolic profiles to identify biochemical variation between the treatment groups. Principal component analysis found a clear distinction between those animals receiving antibiotics and the control animals, with twenty-nine discriminatory compounds of which twenty were down-regulated and nine up-regulated upon treatment. In the treatment group receiving antibiotics for four days, a recovery effect was observed for seven compounds after cessation of antibiotic administration. Thirteen discriminatory compounds could be putatively identified based on their accurate mass, including aconitic acid, benzenediol sulfate, ferulic acid sulfate, hippuric acid, indoxyl sulfate, penicillin G, phenol and vanillin 4-sulfate. The rat urine samples had previously been analyzed by capillary electrophoresis (CE) with MS detection and proton nuclear magnetic resonance (1H NMR) spectroscopy. Using CE–MS and 1H NMR spectroscopy seventeen and twenty-five discriminatory compounds were found, respectively. Both hippuric acid and indoxyl sulfate were detected across all three platforms. Additionally, eight compounds were observed with both HILIC–MS and CE–MS. Overall, HILIC–MS appears to be highly complementary to CE–MS and 1H NMR spectroscopy, identifying additional compounds that discriminate the urine samples from antibiotic-treated and control rats.

The intelligence paradox; will ET get the metabolic syndrome? Lessons from and for Earth

Mankind is facing an unprecedented health challenge in the current pandemic of obesity and diabetes. We propose that this is the inevitable (and predictable) consequence of the evolution of intelligence, which itself could be an expression of life being an information system driven by entropy. Because of its ability to make life more adaptable and robust, intelligence evolved as an efficient adaptive response to the stresses arising from an ever-changing environment. These adaptive responses are encapsulated by the epiphenomena of “hormesis”, a phenomenon we believe to be central to the evolution of intelligence and essential for the maintenance of optimal physiological function and health. Thus, as intelligence evolved, it would eventually reach a cognitive level with the ability to control its environment through technology and have the ability remove all stressors. In effect, it would act to remove the very hormetic factors that had driven its evolution. Mankind may have reached this point, creating an environmental utopia that has reduced the very stimuli necessary for optimal health and the evolution of intelligence – “the intelligence paradox”. One of the hallmarks of this paradox is of course the rising incidence in obesity, diabetes and the metabolic syndrome. This leads to the conclusion that wherever life evolves, here on earth or in another part of the galaxy, the “intelligence paradox’” would be the inevitable side-effect of the evolution of intelligence. ET may not need to just “phone home” but may also need to “phone the local gym”. This suggests another possible reason to explain Fermi’s paradox; Enrico Fermi, the famous physicist, suggested in the 1950s that if extra-terrestrial intelligence was so prevalent, which was a common belief at the time, then where was it? Our suggestion is that if advanced life has got going elsewhere in our galaxy, it can’t afford to explore the galaxy because it has to pay its healthcare costs.

An AeroCom assessment of black carbon in Arctic snow and sea ice

Though many global aerosols models prognose surface deposition, only a few models have been used to directly simulate the radiative effect from black carbon (BC) deposition to snow and sea ice. Here, we apply aerosol deposition fields from 25 models contributing to two phases of the Aerosol Comparisons between Observations and Models (AeroCom) project to simulate and evaluate within-snow BC concentrations and radiative effect in the Arctic. We accomplish this by driving the offline land and sea ice components of the Community Earth System Model with different deposition fields and meteorological conditions from 2004 to 2009, during which an extensive field campaign of BC measurements in Arctic snow occurred. We find that models generally underestimate BC concentrations in snow in northern Russia and Norway, while overestimating BC amounts elsewhere in the Arctic. Although simulated BC distributions in snow are poorly correlated with measurements, mean values are reasonable. The multi-model mean (range) bias in BC concentrations, sampled over the same grid cells, snow depths, and months of measurements, are −4.4 (−13.2 to +10.7) ng g−1 for an earlier phase of AeroCom models (phase I), and +4.1 (−13.0 to +21.4) ng g−1 for a more recent phase of AeroCom models (phase II), compared to the observational mean of 19.2 ng g−1. Factors determining model BC concentrations in Arctic snow include Arctic BC emissions, transport of extra-Arctic aerosols, precipitation, deposition efficiency of aerosols within the Arctic, and meltwater removal of particles in snow. Sensitivity studies show that the model–measurement evaluation is only weakly affected by meltwater scavenging efficiency because most measurements were conducted in non-melting snow. The Arctic (60–90° N) atmospheric residence time for BC in phase II models ranges from 3.7 to 23.2 days, implying large inter-model variation in local BC deposition efficiency. Combined with the fact that most Arctic BC deposition originates from extra-Arctic emissions, these results suggest that aerosol removal processes are a leading source of variation in model performance. The multi-model mean (full range) of Arctic radiative effect from BC in snow is 0.15 (0.07–0.25) W m−2 and 0.18 (0.06–0.28) W m−2 in phase I and phase II models, respectively. After correcting for model biases relative to observed BC concentrations in different regions of the Arctic, we obtain a multi-model mean Arctic radiative effect of 0.17 W m−2 for the combined AeroCom ensembles. Finally, there is a high correlation between modeled BC concentrations sampled over the observational sites and the Arctic as a whole, indicating that the field campaign provided a reasonable sample of the Arctic.

Intercomparison and evaluation of global aerosol microphysical properties among AeroCom models of a range of complexity

Many of the next generation of global climate models will include aerosol schemes which explicitly simulate the microphysical processes that determine the particle size distribution. These models enable aerosol optical properties and cloud condensation nuclei (CCN) concentrations to be determined by fundamental aerosol processes, which should lead to a more physically based simulation of aerosol direct and indirect radiative forcings. This study examines the global variation in particle size distribution simulated by 12 global aerosol microphysics models to quantify model diversity and to identify any common biases against observations. Evaluation against size distribution measurements from a new European network of aerosol supersites shows that the mean model agrees quite well with the observations at many sites on the annual mean, but there are some seasonal biases common to many sites. In particular, at many of these European sites, the accumulation mode number concentration is biased low during winter and Aitken mode concentrations tend to be overestimated in winter and underestimated in summer. At high northern latitudes, the models strongly underpredict Aitken and accumulation particle concentrations compared to the measurements, consistent with previous studies that have highlighted the poor performance of global aerosol models in the Arctic. In the marine boundary layer, the models capture the observed meridional variation in the size distribution, which is dominated by the Aitken mode at high latitudes, with an increasing concentration of accumulation particles with decreasing latitude. Considering vertical profiles, the models reproduce the observed peak in total particle concentrations in the upper troposphere due to new particle formation, although modelled peak concentrations tend to be biased high over Europe. Overall, the multi-model-mean data set simulates the global variation of the particle size distribution with a good degree of skill, suggesting that most of the individual global aerosol microphysics models are performing well, although the large model diversity indicates that some models are in poor agreement with the observations. Further work is required to better constrain size-resolved primary and secondary particle number sources, and an improved understanding of nucleation and growth (e.g. the role of nitrate and secondary organics) will improve the fidelity of simulated particle size distributions.

The AeroCom evaluation and intercomparison of organic aerosol in global models

This paper evaluates the current status of global modeling of the organic aerosol (OA) in the troposphere and analyzes the differences between models as well as between models and observations. Thirty-one global chemistry transport models (CTMs) and general circulation models (GCMs) have participated in this intercomparison, in the framework of AeroCom phase II. The simulation of OA varies greatly between models in terms of the magnitude of primary emissions, secondary OA (SOA) formation, the number of OA species used (2 to 62), the complexity of OA parameterizations (gas-particle partitioning, chemical aging, multiphase chemistry, aerosol microphysics), and the OA physical, chemical and optical properties. The diversity of the global OA simulation results has increased since earlier AeroCom experiments, mainly due to the increasing complexity of the SOA parameterization in models, and the implementation of new, highly uncertain, OA sources. Diversity of over one order of magnitude exists in the modeled vertical distribution of OA concentrations that deserves a dedicated future study. Furthermore, although the OA / OC ratio depends on OA sources and atmospheric processing, and is important for model evaluation against OA and OC observations, it is resolved only by a few global models. The median global primary OA (POA) source strength is 56 Tg a−1 (range 34–144 Tg a−1) and the median SOA source strength (natural and anthropogenic) is 19 Tg a−1 (range 13–121 Tg a−1). Among the models that take into account the semi-volatile SOA nature, the median source is calculated to be 51 Tg a−1 (range 16–121 Tg a−1), much larger than the median value of the models that calculate SOA in a more simplistic way (19 Tg a−1; range 13–20 Tg a−1, with one model at 37 Tg a−1). The median atmospheric burden of OA is 1.4 Tg (24 models in the range of 0.6–2.0 Tg and 4 between 2.0 and 3.8 Tg), with a median OA lifetime of 5.4 days (range 3.8–9.6 days). In models that reported both OA and sulfate burdens, the median value of the OA/sulfate burden ratio is calculated to be 0.77; 13 models calculate a ratio lower than 1, and 9 models higher than 1. For 26 models that reported OA deposition fluxes, the median wet removal is 70 Tg a−1 (range 28–209 Tg a−1), which is on average 85% of the total OA deposition. Fine aerosol organic carbon (OC) and OA observations from continuous monitoring networks and individual field campaigns have been used for model evaluation. At urban locations, the model–observation comparison indicates missing knowledge on anthropogenic OA sources, both strength and seasonality. The combined model–measurements analysis suggests the existence of increased OA levels during summer due to biogenic SOA formation over large areas of the USA that can be of the same order of magnitude as the POA, even at urban locations, and contribute to the measured urban seasonal pattern. Global models are able to simulate the high secondary character of OA observed in the atmosphere as a result of SOA formation and POA aging, although the amount of OA present in the atmosphere remains largely underestimated, with a mean normalized bias (MNB) equal to −0.62 (−0.51) based on the comparison against OC (OA) urban data of all models at the surface, −0.15 (+0.51) when compared with remote measurements, and −0.30 for marine locations with OC data. The mean temporal correlations across all stations are low when compared with OC (OA) measurements: 0.47 (0.52) for urban stations, 0.39 (0.37) for remote stations, and 0.25 for marine stations with OC data. The combination of high (negative) MNB and higher correlation at urban stations when compared with the low MNB and lower correlation at remote sites suggests that knowledge about the processes that govern aerosol processing, transport and removal, on top of their sources, is important at the remote stations. There is no clear change in model skill with increasing model complexity with regard to OC or OA mass concentration. However, the complexity is needed in models in order to distinguish between anthropogenic and natural OA as needed for climate mitigation, and to calculate the impact of OA on climate accurately.

Aerosol microphysics simulations of the Mt.~Pinatubo eruption with the UM-UKCA composition-climate model

We use a stratosphere–troposphere composition–climate model with interactive sulfur chemistry and aerosol microphysics, to investigate the effect of the 1991 Mount Pinatubo eruption on stratospheric aerosol properties. Satellite measurements indicate that shortly after the eruption, between 14 and 23 Tg of SO2 (7 to 11.5 Tg of sulfur) was present in the tropical stratosphere. Best estimates of the peak global stratospheric aerosol burden are in the range 19 to 26 Tg, or 3.7 to 6.7 Tg of sulfur assuming a composition of between 59 and 77 % H2SO4. In light of this large uncertainty range, we performed two main simulations with 10 and 20 Tg of SO2 injected into the tropical lower stratosphere. Simulated stratospheric aerosol properties through the 1991 to 1995 period are compared against a range of available satellite and in situ measurements. Stratospheric aerosol optical depth (sAOD) and effective radius from both simulations show good qualitative agreement with the observations, with the timing of peak sAOD and decay timescale matching well with the observations in the tropics and mid-latitudes. However, injecting 20 Tg gives a factor of 2 too high stratospheric aerosol mass burden compared to the satellite data, with consequent strong high biases in simulated sAOD and surface area density, with the 10 Tg injection in much better agreement. Our model cannot explain the large fraction of the injected sulfur that the satellite-derived SO2 and aerosol burdens indicate was removed within the first few months after the eruption. We suggest that either there is an additional alternative loss pathway for the SO2 not included in our model (e.g. via accommodation into ash or ice in the volcanic cloud) or that a larger proportion of the injected sulfur was removed via cross-tropopause transport than in our simulations. We also critically evaluate the simulated evolution of the particle size distribution, comparing in detail to balloon-borne optical particle counter (OPC) measurements from Laramie, Wyoming, USA (41° N). Overall, the model captures remarkably well the complex variations in particle concentration profiles across the different OPC size channels. However, for the 19 to 27 km injection height-range used here, both runs have a modest high bias in the lowermost stratosphere for the finest particles (radii less than 250 nm), and the decay timescale is longer in the model for these particles, with a much later return to background conditions. Also, whereas the 10 Tg run compared best to the satellite measurements, a significant low bias is apparent in the coarser size channels in the volcanically perturbed lower stratosphere. Overall, our results suggest that, with appropriate calibration, aerosol microphysics models are capable of capturing the observed variation in particle size distribution in the stratosphere across both volcanically perturbed and quiescent conditions. Furthermore, additional sensitivity simulations suggest that predictions with the models are robust to uncertainties in sub-grid particle formation and nucleation rates in the stratosphere.

The importance of vertical velocity variability for estimates of the indirect aerosol effects

The activation of aerosols to form cloud droplets is dependent upon vertical velocities whose local variability is not typically resolved at the GCM grid scale. Consequently, it is necessary to represent the subgrid-scale variability of vertical velocity in the calculation of cloud droplet number concentration. This study uses the UK Chemistry and Aerosols community model (UKCA) within the Hadley Centre Global Environmental Model (HadGEM3), coupled for the first time to an explicit aerosol activation parameterisation, and hence known as UKCA-Activate. We explore the range of uncertainty in estimates of the indirect aerosol effects attributable to the choice of parameterisation of the subgrid-scale variability of vertical velocity in HadGEM-UKCA. Results of simulations demonstrate that the use of a characteristic vertical velocity cannot replicate results derived with a distribution of vertical velocities, and is to be discouraged in GCMs. This study focuses on the effect of the variance (σw2) of a Gaussian pdf (probability density function) of vertical velocity. Fixed values of σw (spanning the range measured in situ by nine flight campaigns found in the literature) and a configuration in which σw depends on turbulent kinetic energy are tested. Results from the mid-range fixed σw and TKE-based configurations both compare well with observed vertical velocity distributions and cloud droplet number concentrations. The radiative flux perturbation due to the total effects of anthropogenic aerosol is estimated at −1.9 W m−2 with σw = 0.1 m s−1, −2.1 W m−2 with σw derived from TKE, −2.25 W m−2 with σw = 0.4 m s−1, and −2.3 W m−2 with σw = 0.7 m s−1. The breadth of this range is 0.4 W m−2, which is comparable to a substantial fraction of the total diversity of current aerosol forcing estimates. Reducing the uncertainty in the parameterisation of σw would therefore be an important step towards reducing the uncertainty in estimates of the indirect aerosol effects. Detailed examination of regional radiative flux perturbations reveals that aerosol microphysics can be responsible for some climate-relevant radiative effects, highlighting the importance of including microphysical aerosol processes in GCMs.

Effect of cinnamon on gastric emptying, arterial stiffness, postprandial lipemia, glycemia, and appetite responses to high-fat breakfast

Abstract BACKGROUND: Cinnamon has been shown to delay gastric emptying of a high-carbohydrate meal and reduce postprandial glycemia in healthy adults. However, it is dietary fat which is implicated in the etiology and is associated with obesity, type 2 diabetes and cardiovascular disease. We aimed to determine the effect of 3 g cinnamon (Cinnamomum zeylanicum) on GE, postprandial lipemic and glycemic responses, oxidative stress, arterial stiffness, as well as appetite sensations and subsequent food intake following a high-fat meal. METHODS: A single-blind randomized crossover study assessed nine healthy, young subjects. GE rate of a high-fat meal supplemented with 3 g cinnamon or placebo was determined using the 13C octanoic acid breath test. Breath, blood samples and subjective appetite ratings were collected in the fasted and during the 360 min postprandial period, followed by an ad libitum buffet meal. Gastric emptying and 1-day fatty acid intake relationships were also examined. RESULTS: Cinnamon did not change gastric emptying parameters, postprandial triacylglycerol or glucose concentrations, oxidative stress, arterial function or appetite (p < 0.05). Strong relationships were evident (p < 0.05) between GE Thalf and 1-day palmitoleic acid (r = -0.78), eiconsenoic acid (r = -0.84) and total omega-3 intake (r = -0.72). The ingestion of 3 g cinnamon had no effect on GE, arterial stiffness and oxidative stress following a HF meal. CONCLUSIONS: 3 g cinnamon did not alter the postprandial response to a high-fat test meal. We find no evidence to support the use of 3 g cinnamon supplementation for the prevention or treatment of metabolic disease. Dietary fatty acid intake requires consideration in future gastrointestinal studies.

Robustness despite uncertainty: regional climate data reveal the dominant role of humans in explaining global extinctions of Late Quaternary megafauna

Debate over the late Quaternary megafaunal extinctions has focussed on whether human colonisation or climatic changes were more important drivers of extinction, with few extinctions being unambiguously attributable to either. Most analyses have been geographically or taxonomically restricted and the few quantitative global analyses have been limited by coarse temporal resolution or overly simplified climate reconstructions or proxies. We present a global analysis of the causes of these extinctions which uses high-resolution climate reconstructions and explicitly investigates the sensitivity of our results to uncertainty in the palaeological record. Our results show that human colonisation was the dominant driver of megafaunal extinction across the world but that climatic factors were also important. We identify the geographic regions where future research is likely to have the most impact, with our models reliably predicting extinctions across most of the world, with the notable exception of mainland Asia where we fail to explain the apparently low rate of extinction found in in the fossil record. Our results are highly robust to uncertainties in the palaeological record, and our main conclusions are unlikely to change qualitatively following minor improvements or changes in the dates of extinctions and human colonisation.

Modelled and observed changes in aerosols and surface solar radiation over Europe between 1960 and 2009

Substantial changes in anthropogenic aerosols and precursor gas emissions have occurred over recent decades due to the implementation of air pollution control legislation and economic growth. The response of atmospheric aerosols to these changes and the impact on climate are poorly constrained, particularly in studies using detailed aerosol chemistry–climate models. Here we compare the HadGEM3-UKCA (Hadley Centre Global Environment Model-United Kingdom Chemistry and Aerosols) coupled chemistry–climate model for the period 1960–2009 against extensive ground-based observations of sulfate aerosol mass (1978–2009), total suspended particle matter (SPM, 1978–1998), PM10 (1997–2009), aerosol optical depth (AOD, 2000–2009), aerosol size distributions (2008–2009) and surface solar radiation (SSR, 1960–2009) over Europe. The model underestimates observed sulfate aerosol mass (normalised mean bias factor (NMBF) = −0.4), SPM (NMBF = −0.9), PM10 (NMBF = −0.2), aerosol number concentrations (N30 NMBF = −0.85; N50 NMBF = −0.65; and N100 NMBF = −0.96) and AOD (NMBF = −0.01) but slightly overpredicts SSR (NMBF = 0.02). Trends in aerosol over the observational period are well simulated by the model, with observed (simulated) changes in sulfate of −68 % (−78 %), SPM of −42 % (−20 %), PM10 of −9 % (−8 %) and AOD of −11 % (−14 %). Discrepancies in the magnitude of simulated aerosol mass do not affect the ability of the model to reproduce the observed SSR trends. The positive change in observed European SSR (5 %) during 1990–2009 ("brightening") is better reproduced by the model when aerosol radiative effects (ARE) are included (3 %), compared to simulations where ARE are excluded (0.2 %). The simulated top-of-the-atmosphere aerosol radiative forcing over Europe under all-sky conditions increased by > 3.0 W m−2 during the period 1970–2009 in response to changes in anthropogenic emissions and aerosol concentrations.

The impact of European legislative and technology measures to reduce air pollutants on air quality, human health and climate

European air quality legislation has reduced emissions of air pollutants across Europe since the 1970s, affecting air quality, human health and regional climate. We used a coupled composition-climate model to simulate the impacts of European air quality legislation and technology measures implemented between 1970 and 2010. We contrast simulations using two emission scenarios; one with actual emissions in 2010 and the other with emissions that would have occurred in 2010 in the absence of technological improvements and end-of-pipe treatment measures in the energy, industrial and road transport sectors. European emissions of sulphur dioxide, black carbon (BC) and organic carbon in 2010 are 53%, 59% and 32% lower respectively compared to emissions that would have occurred in 2010 in the absence of legislative and technology measures. These emission reductions decreased simulated European annual mean concentrations of fine particulate matter(PM2.5) by 35%, sulphate by 44%, BC by 56% and particulate organic matter by 23%. The reduction in PM2.5 concentrations is calculated to have prevented 80 000 (37 000–116 000, at 95% confidence intervals) premature deaths annually across the European Union, resulting in a perceived financial benefit to society of US$232 billion annually (1.4% of 2010 EU GDP). The reduction in aerosol concentrations due to legislative and technology measures caused a positive change in the aerosol radiative effect at the top of atmosphere, reduced atmospheric absorption and also increased the amount of solar radiation incident at the surface over Europe. We used an energy budget approximation to estimate that these changes in the radiative balance have increased European annual mean surface temperatures and precipitation by 0.45 ± 0.11 °C and by 13 ± 0.8 mm yr−1 respectively. Our results show that the implementation of European legislation and technological improvements to reduce the emission of air pollutants has improved air quality and human health over Europe, as well as having an unintended impact on the regional radiative balance and climate.