Albert Arking

Association of human aging with a functional variant of klotho

Mice deficient in Klotho gene expression exhibit a syndrome resembling premature human aging. To determine whether variation in the human KLOTHO locus contributes to survival, we applied two newly characterized polymorphic microsatellite markers flanking the gene in a population-based association study. In a cohort chosen for its homogeneity, Bohemian Czechs, we demonstrated significant differences in selected marker allele frequencies between newborn and elderly individuals (P < 0.05). These results precipitated a search for functional variants of klotho. We identified an allele, termed KL-VS, containing six sequence variants in complete linkage disequilibrium, two of which result in amino acid substitutions F352V and C370S. Homozygous elderly individuals were underrepresented in three distinct populations: Bohemian Czechs, Baltimore Caucasians, and Baltimore African-Americans [combined odds ratio (OR) = 2.59, P < 0.0023]. In a transient transfection assay, secreted levels of klotho harboring V352 are reduced 6-fold, whereas extracellular levels of the S370 form are increased 2.9-fold. The V352/S370 double mutant exhibits an intermediate phenotype (1.6-fold increase), providing a rare example of intragenic complementation in cis by human single nucleotide polymorphisms. The remarkable conservation of F352 among homologous proteins suggests that it is functionally important. The corresponding substitution, F289V, in the closest human klotho paralog with a known substrate, cBGL1, completely eliminates its ability to cleave p-nitrophenyl-β-d-glucoside. These results suggest that the KL-VS allele influences the trafficking and catalytic activity of klotho, and that variation in klotho function contributes to heterogeneity in the onset and severity of human age-related phenotypes.

Association Between a Functional Variant of the KLOTHO Gene and High-Density Lipoprotein Cholesterol, Blood Pressure, Stroke, and Longevity

We previously identified a functional variant of KLOTHO, termed KL-VS, that is associated with human aging and early-onset occult coronary artery disease. Here, we determine whether the KL-VS allele influences cardiovascular disease risk factors, cardiovascular events, and ultimately, mortality. A total of 525 Ashkenazi Jews composed of 216 probands (age ≥95 years) and 309 unrelated individuals (ages 51 to 94) were genotyped for the KL-VS allele. In concordance with our previous data in Czech individuals (age ≥79; P<0.01), a heterozygous advantage for longevity was observed for individuals ≥79 years of age (P<0.004). Combined analysis indicates a 1.57-fold (95% CI, 1.23 to 1.98) increased odds ratio (OR) for 5-year survival in two independent populations (P<0.0002). Cardiovascular disease risk factors were assessed through multivariate regression analysis, demonstrating that high-density lipoprotein cholesterol (HDL-C; P<0.05) and systolic blood pressure (SBP; P<0.008) are associated with KL-VS genotype. History of vascular events was analyzed using logistic regression, indicating that after adjustment for traditional risk factors, heterozygous individuals were at significantly lower risk for stroke than wild-type individuals (OR, 5.88; 95% CI, 1.18 to 29.41), whereas homozygous KL-VS individuals had the highest risk (OR, 30.65; 95% CI, 2.55 to 368.00). Similarly, prospective analysis of mortality in probands using Cox regression indicates that wild-type individuals have a 2.15-fold (95% CI, 1.18 to 3.91) and homozygous KL-VS individuals a 4.49-fold (95% CI, 1.35 to 14.97) increase in relative risk for mortality after adjusting for potential confounders. Thus, cross-sectional and prospective studies confirm a genetic model in which the KL-VS allele confers a heterozygous advantage in conjunction with a marked homozygous disadvantage for HDL-C levels, SBP, stroke, and longevity.

The Radiative Effects of Clouds and their Impact on Climate

Our knowledge of the direct role of clouds in long-term climate change is examined in an overview of key results published over the last 15 or 20 years, along with some relevant unpublished model studies. The focus is on 1) the impact of clouds on the incoming and outgoing radiation at the top of the atmosphere, and 2) the two-way interaction of clouds with other variables of the climate system—i.e., the cloud/climate feedback problem—as revealed by climate model simulations. A common framework is established for comparing results from different investigations. The total effect of clouds on radiative fluxes at the top of the atmosphere—specifically, the difference in flux between average conditions and cloud-free conditions, often called cloud forcing–has been derived from earth radiation budget measurements by several investigators using various data sources and methods. There is general agreement that the annual global mean effect of clouds is to cool the climate system, but there is significant disagre...

Absorption of Solar Energy in the Atmosphere: Discrepancy Between Model and Observations

An atmospheric general circulation model, which assimilates data from daily observations of temperature, humidity, wind, and sea-level air pressure, was compared with a set of observations that combines satellite and ground-based measurements of solar flux. The comparison reveals that the model underestimates by 25 to 30 watts per square meter the amount of solar energy absorbed by Earths atmosphere. Contrary to some recent reports, clouds have little or no overall effect on atmospheric absorption, a consistent feature of both the observations and the model. Of several variables considered, water vapor appears to be the dominant influence on atmospheric absorption.

The Influence of Line Shape and Band Structure on Temperatures in Planetary Atmospheres

Abstract Numerical experiments are performed to examine the effects of line shape and band structure on the radiative equilibrium temperature profile in planetary atmospheres. In order to accurately determine these effects, a method for calculating radiative terms is developed which avoids the usual approximations. It differs from the more commonly used methods in that it allows arbitrary dependence of the absorption coefficient on wavenumber, without requiring tedious line-by-line integration and without the constraints of band models. The present formulation is restricted to homogeneous atmospheres but the concept can be extended to the more general case. The numerical experiments reveal that the line shape and band structure of the absorbing gases have a large effect on temperatures in the higher layers of the atmosphere (corresponding to the stratosphere and mesosphere). The more non-grey the spectrum, i.e., the higher the peaks and the deeper the troughs in the spectrum, the lower the temperature.

On Solar Energy Disposition: A Perspective from Observation and Modeling

Abstract Solar energy disposition (SED) concerns the amount of solar radiation reflected to space, absorbed in the atmosphere, and absorbed at the surface. The state of knowledge on SED is examined by comparing eight datasets from surface and satellite observation and modeling by general circulation models. The discrepancies among these contemporary estimates of SED are so large that wisdom on conventional SED is wanting. Thanks to satellite observations, the earths radiation budget (ERB) at the top of the atmosphere is reasonably well known. Current GCMs manage to reproduce a reasonable global and annual mean ERB, but often fail to simulate the variations in ERB associated with certain cloud regimes such as tropical convection and storm tracks. In comparison to ERB, knowledge of the surface radiation budget (SRB) and the atmospheric radiation budget (ARB) is still rather poor, owing to the inherent problems in both in situ observations and remote sensing. The major shortcoming of in situ observations li...

Computation of Infrared Cooling Rates in the Water Vapor Bands

Abstract A fast but accurate method for calculating the infrared radiative terms due to water vapor has been developed. It makes use of the behavior in the far wings of absorption lines to scale transmission along an inhomogencous path to an equivalent homogeneous path. Rather than using standard conditions for scaling, the reference temperatures and pressures are chosen in this study to correspond to the-regions where cooling is most significant. This greatly increases the accuracy of the new method. Compared to line-by-line calculations, the new method has errors up to 4% of the maximum cooling rate, while a commonly used method based on the Goody band model (Rodgers and Walshaw, 1966) introduces errors up to 11%. The effect of temperature dependence of transmittance has also been evaluated; the cooling rate errors range up to 11% when the temperature-dependence is ignored. In addition to being more accurate, the new method is much faster than those based on the Goody band model.

Bringing Climate Models into Agreement with Observations of Atmospheric Absorption

Abstract A comparison of the output of two data assimilation models with a quasi-global, multiyear set of monthly mean observations shows that the models underestimate the amount of solar energy absorbed in the atmosphere by 15–30 W m−2, out of a total of ∼80 W m−2. In addition, observations show a much stronger dependence of absorption on column water vapor than models. Here the author analyzes absorption measured between two aircraft on a clear day during the Atmospheric Radiation Measurement (ARM) Enhanced Shortwave Experiment (ARESE) and finds a similarly strong dependence of absorption on water vapor. This common feature, in disparate types of observations, suggests the possible existence of appreciable continuum absorption in the water vapor spectrum. Various formulations of continuum absorption are tested against the aircraft observations and against the monthly mean dataset. In both cases, the addition of continuum absorption brings the models substantially closer to the observations, especially i...

Climate Studies with a Multi-Layer Energy Balance Model. Part I: Model Description and Sensitivity to the Solar Constant

Abstract A nine-layer, zonally averaged, steady-state model has been developed for use in climate sensitivity studies. The model is based upon thermal energy balance and includes recently developed accurate treatment of radiative transfer, parameterized meridional and vertical energy transport, and thermodynamic interaction between the surface and the atmosphere. Cloud cover and relative humidity are prescribed parameters. Using present day boundary conditions for the Northern Hemisphere, the simulated temperature field, heat fluxes and radiation quantities are in good agreement with observations. In a study of sensitivity to changes in the solar constant, the model exhibits a high degree of nonlinearity. The change in the hemispheric mean surface temperature is +3.1°C in response to a 2% increase in the solar constant and −4.3°C in response to a 2% decrease in the solar constant. The sensitivity varies with latitude. In the polar region it is about three times larger than in the tropics, due mostly to th...

The influence of clouds and water vapor on atmospheric absorption

Observations during a field experiment in Oklahoma in the fall of 1995 have been analyzed to show the influence of clouds and water vapor on broadband absorption of solar radiation in the atmosphere. The fraction of solar flux incident at the top of the atmosphere absorbed during 34 days was 0.24±0.04. For a 7-day subset during which skies were clear, it was 0.22±0.02. Both clouds and water vapor contribute to day-to-day variability. The water vapor effect is systematic, increasing absorption by 0.04-0.05 per g cm -2 increase of column water vapor. Clouds, on the other hand, increase or decrease total column absorption, depending on cloud configuration. Most of the average cloud effect is due to water vapor, which was highly correlated with cloud amount during the experiment. Overall, model calculations underestimate atmospheric absorption by 0.06, with 25-55% of the discrepancy associated with water vapor, ∼15% with clouds, and the remaining 30-60% independent of either variable.