Long-Lived Individuals Show a Lower Burden of Variants Predisposing to Age-Related Diseases and a Higher Polygenic Longevity Score.

Longevity is a complex phenotype influenced by both environmental and genetic factors. The genetic contribution is estimated at about 25%. Despite extensive research efforts, only a few longevity genes have been validated across populations. Long-lived individuals (LLI) reach extreme ages with a relative low prevalence of chronic disability and major age-related diseases (ARDs). We tested whether the protection from ARDs in LLI can partly be attributed to genetic factors by calculating polygenic risk scores (PRSs) for seven common late-life diseases (Alzheimer's disease (AD), atrial fibrillation (AF), coronary artery disease (CAD), colorectal cancer (CRC), ischemic stroke (ISS), Parkinson's disease (PD) and type 2 diabetes (T2D)). The examined sample comprised 1351 German LLI (≥94 years, including 643 centenarians) and 4680 German younger controls. For all ARD-PRSs tested, the LLI had significantly lower scores than the younger control individuals (areas under the curve (AUCs): ISS = 0.59, p = 2.84 × 10-35; AD = 0.59, p = 3.16 × 10-25; AF = 0.57, p = 1.07 × 10-16; CAD = 0.56, p = 1.88 × 10-12; CRC = 0.52, p = 5.85 × 10-3; PD = 0.52, p = 1.91 × 10-3; T2D = 0.51, p = 2.61 × 10-3). We combined the individual ARD-PRSs into a meta-PRS (AUC = 0.64, p = 6.45 × 10-15). We also generated two genome-wide polygenic scores for longevity, one with and one without the TOMM40/APOE/APOC1 gene region (AUC (incl. TOMM40/APOE/APOC1) = 0.56, p = 1.45 × 10-5, seven variants; AUC (excl. TOMM40/APOE/APOC1) = 0.55, p = 9.85 × 10-3, 10,361 variants). Furthermore, the inclusion of nine markers from the excluded region (not in LD with each other) plus the APOE haplotype into the model raised the AUC from 0.55 to 0.61. Thus, our results highlight the importance of TOMM40/APOE/APOC1 as a longevity hub.

Laser-controlled adaptive optics for beam quality improvements in a multi-pass thin-disk amplifier.

We devise a laser-controlled adaptive optical element that operates intracavity under high-intensity radiation. This element substitutes a conventional mechanically deformable mirror and is free of critical heat-sensitive components and electronics. The deformation mechanism is based on the projection of a continuous-wave control laser onto a specially designed mirror. Mounted to a water-cooled heat sink, the mirror can handle laser radiation beyond 3 MW/cm2. The properties of the adaptive optical element, including the maximum correctable wavefront pitch of 800 nm, are discussed. The successful implementation in a multi-pass thin-disk amplifier is presented. An improvement of the beam quality by a factor of three is achieved. We identify measures to enhance the performance of the adaptive optics towards efficient operation in a high-power laser system.

Continuous-wave, double-pass second-harmonic generation with 60% efficiency in a single MgO:PPSLT crystal.

We present a double-pass scheme for high-efficiency, high-power, second-harmonic generation (SHG) in a single MgO-doped periodically poled stoichiometric lithium tantalate (MgO:PPSLT) crystal. The device is pumped by a single-frequency, continuous-wave fiber amplifier laser system at a wavelength of 1091 nm. For the double-pass scheme, a conversion efficiency of 60% and a harmonic power of 12.8 W at a wavelength of 545.5 nm with a high beam quality of (M2<1.2) is achieved. Compared to single-pass SHG, a double-pass enhancement factor of more than two is observed at the highest fundamental pump power.

Current allele distribution of the human longevity gene APOE in Europe can mainly be explained by ancient admixture.

Variation in apolipoprotein E (APOE) has been shown to have the strongest genetic effect on human longevity. The aim of this study was to unravel the evolutionary history of the three major APOE alleles in Europe by analysing ancient samples up to 12,000 years old. We detected significant allele frequency shifts between populations and over time. Our analyses indicated that selection led to large frequency differences between the earliest European populations (i.e., hunter-gatherers vs. first farmers), possibly due to changes in diet/lifestyle. In contrast, the allele distributions in populations from ~4000 BCE onward can mainly be explained by admixture, suggesting that it also played an important role in shaping current APOE variation. In any case, the resulting allele frequencies strongly influence the predisposition for longevity today, likely as a consequence of past adaptations and demographic processes.

Triple resonant four-wave mixing boosts the yield of continuous coherent vacuum ultraviolet generation.

Efficient continuous-wave four-wave mixing by using three different fundamental wavelengths with individual detunings to resonances of the nonlinear medium is shown. Up to 6 µW of vacuum ultraviolet light at 121 nm can be generated, which corresponds to an increase of three orders of magnitude in efficiency. This opens the field of quantum information processing by Rydberg entanglement of trapped ions.

Continuous-wave spontaneous lasing in mercury pumped by resonant two-photon absorption.

We demonstrate the first cw two-photon absorption laser-induced stimulated emission. The 7(1)S(0)-6(1)P(1) transition in mercury at a 1014 nm wavelength is used, and selective lasing of different isotopes is observed.

Continuous-wave Lyman-alpha generation with solid-state lasers.

A coherent continuous-wave Lyman-alpha source based on four-wave sum-frequency mixing in mercury vapor has been realized with solid-state lasers. The third-order nonlinear susceptibility is enhanced by the 6(1)S - 7(1)S two-photon resonance and the near 6(1)S-6(3)P one-photon resonance. The phase matching curve for this four-wave mixing scheme is observed for the first time. In addition we investigate the two-photon enhancement of the Lyman-alpha yield and observe that the maxima of Lyman-alpha generation are shifted compared to the two-photon resonances of the different isotopes.

4W continuous-wave narrow-linewidth tunable solid-state laser source at 546nm by externally frequency doubling a ytterbium-doped single-mode fiber laser system.

A high-power continuous-wave coherent light source at 545.5nm is described. We use 8.3W from a solid-state ytterbium-doped single-mode fiber oscillator/amplifier system as input into an external frequency doubling stage. This system produces up to 4.1W of stable green single-frequency laser radiation. We characterize the light source by performing absorption spectroscopy on iodine across the full tuning range of the fiber laser and saturation spectroscopy on one strong iodine line of the doppler-broadened spectrum.