All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In ...accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan.
Nonlinear optical phenomena in nanostructured materials have been challenging our perceptions of nonlinear optical processes that have been explored since the invention of lasers. For example, the ...ability to control optical field confinement, enhancement, and scattering almost independently allows nonlinear frequency conversion efficiencies to be enhanced by many orders of magnitude compared to bulk materials. Also, the subwavelength length scale renders phase matching issues irrelevant. Compared with plasmonic nanostructures, dielectric resonator metamaterials show great promise for enhanced nonlinear optical processes due to their larger mode volumes. Here, we present, for the first time, resonantly enhanced second-harmonic generation (SHG) using gallium arsenide (GaAs) based dielectric metasurfaces. Using arrays of cylindrical resonators we observe SHG enhancement factors as large as 104 relative to unpatterned GaAs. At the magnetic dipole resonance, we measure an absolute nonlinear conversion efficiency of ∼2 × 10–5 with ∼3.4 GW/cm2 pump intensity. The polarization properties of the SHG reveal that both bulk and surface nonlinearities play important roles in the observed nonlinear process.
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IJS, KILJ, NUK, PNG, UL, UM
Ultrafast control of the polarization state of light may enable a plethora of applications in optics, chemistry and biology. However, conventional polarizing elements, such as polarizers and ...waveplates, are either static or possess only gigahertz switching speeds. Here, with the aid of high-mobility indium-doped cadmium oxide (CdO) as the gateway plasmonic material, we realize a high-quality factor Berreman-type perfect absorber at a wavelength of 2.08 mu m. On sub-bandgap optical pumping, the perfect absorption resonance strongly redshifts because of the transient increase of the ensemble-averaged effective electron mass of CdO, which leads to an absolute change in the p-polarized reflectance from 1.0 to 86.3%. By combining the exceedingly high modulation depth with the polarization selectivity of the perfect absorber, we experimentally demonstrate a reflective polarizer with a polarization extinction ratio of 91 that can be switched on and off within 800fs.
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IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UL, UM, UPUK
A frequency mixer is a nonlinear device that combines electromagnetic waves to create waves at new frequencies. Mixers are ubiquitous components in modern radio-frequency technology and microwave ...signal processing. The development of versatile frequency mixers for optical frequencies remains challenging: such devices generally rely on weak nonlinear optical processes and, thus, must satisfy phase-matching conditions. Here we utilize a GaAs-based dielectric metasurface to demonstrate an optical frequency mixer that concurrently generates eleven new frequencies spanning the ultraviolet to near-infrared. The even and odd order nonlinearities of GaAs enable our observation of second-harmonic, third-harmonic, and fourth-harmonic generation, sum-frequency generation, two-photon absorption-induced photoluminescence, four-wave mixing and six-wave mixing. The simultaneous occurrence of these seven nonlinear processes is assisted by the combined effects of strong intrinsic material nonlinearities, enhanced electromagnetic fields, and relaxed phase-matching requirements. Such ultracompact optical mixers may enable a plethora of applications in biology, chemistry, sensing, communications, and quantum optics.
Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to ...decreases in tissue function and regenerative capacity
. Changes to DNA methylation patterns over time form the basis of ageing clocks
, but whether older individuals retain the information needed to restore these patterns-and, if so, whether this could improve tissue function-is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity
. Using the eye as a model CNS tissue, here we show that ectopic expression of Oct4 (also known as Pou5f1), Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information-encoded in part by DNA methylation-that can be accessed to improve tissue function and promote regeneration in vivo.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
NAD+ in COVID-19 and viral infections Zheng, Minyan; Schultz, Michael B.; Sinclair, David A.
Trends in immunology,
04/2022, Volume:
43, Issue:
4
Journal Article
Peer reviewed
Open access
NAD+, as an emerging regulator of immune responses during viral infections, may be a promising therapeutic target for coronavirus disease 2019 (COVID-19). In this Opinion, we suggest that ...interventions that boost NAD+ levels might promote antiviral defense and suppress uncontrolled inflammation. We discuss the association between low NAD+ concentrations and risk factors for poor COVID-19 outcomes, including aging and common comorbidities. Mechanistically, we outline how viral infections can further deplete NAD+ and its roles in antiviral defense and inflammation. We also describe how coronaviruses can subvert NAD+-mediated actions via genes that remove NAD+ modifications and activate the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Finally, we explore ongoing approaches to boost NAD+ concentrations in the clinic to putatively increase antiviral responses while curtailing hyperinflammation.
NAD+ can exert both antiviral and anti-inflammatory effects in mice and humans, which might be beneficial during coronavirus disease 2019 (COVID-19) infections.Compared with healthy individuals, NAD+ concentrations in tissues and organs are lower in older individuals and in patients with diseases associated with severe COVID-19 symptoms, including diabetes and cardiovascular disease.Viral infections, including coronavirus infections, have been reported to further deplete cellular NAD+ stores.Many NAD+-dependent enzymes, including members of the sirtuin and poly-ADP-ribose polymerase (PARP) families, display potent antiviral activities.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a variety of viruses possess ADP-ribosyl hydrolase activity, which counteracts the activity of PARPs.Viruses such as SARS-CoV-2 can hyperactivate the immune system by activating nuclear factor kappa B (NF-κB) and the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, potentially leading to deadly cytokine storms. NAD+-boosting compounds may counteract these processes.Several NAD+-boosting compounds and molecules that target NAD+-producing or -consuming enzymes are in clinical development as putative anti-inflammatory or antiviral drugs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse ...aspects of aging, in part, by activating sirtuin deacylases (SIRT1–SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD+ levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly.
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•Reduced blood flow with age is due to loss of endothelial NAD+-SIRT1 activity•NAD+ and H2S control muscle angiogenesis and increase endurance in old mice•The NAD precursor NMN mimics and augments exercise by inhibiting NICD-Notch•Neovascularization is as important as mitochondria for rejuvenating muscle
Endothelial SIRT1 regulates pro-angiogenic signals secreted from myocytes and improves muscle health. Treatment of mice with NAD precursor nicotinamide mononucleotide improves vascular and increases endurance in aging mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
High-harmonic generation (HHG) is a signature optical phenomenon of strongly driven, nonlinear optical systems. Specifically, the understanding of the HHG process in rare gases has played a key role ...in the development of attosecond science1. Recently, HHG has also been reported in solids, providing novel opportunities such as controlling strong-field and attosecond processes in dense optical media down to the nanoscale2. Here, we report HHG from a low-loss, indium-doped cadmium oxide thin film by leveraging the epsilon-near-zero (ENZ) effect3–8, whereby the real part of the material’s permittivity in certain spectral ranges vanishes, as well as the associated large resonant enhancement of the driving laser field. We find that ENZ-assisted harmonics exhibit a pronounced spectral redshift as well as linewidth broadening, resulting from the photo induced electron heating and the consequent time-dependent ENZ wavelength of the material. Our results provide a new platform to study strong-field and ultrafast electron dynamics in ENZ materials, reveal new degrees of freedom for spectral and temporal control of HHG, and open up the possibilities of compact solid-state attosecond light sources.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The identification of genes and interventions that slow or reverse aging is hampered by the lack of non-invasive metrics that can predict the life expectancy of pre-clinical models. Frailty Indices ...(FIs) in mice are composite measures of health that are cost-effective and non-invasive, but whether they can accurately predict health and lifespan is not known. Here, mouse FIs are scored longitudinally until death and machine learning is employed to develop two clocks. A random forest regression is trained on FI components for chronological age to generate the FRIGHT (Frailty Inferred Geriatric Health Timeline) clock, a strong predictor of chronological age. A second model is trained on remaining lifespan to generate the AFRAID (Analysis of Frailty and Death) clock, which accurately predicts life expectancy and the efficacy of a lifespan-extending intervention up to a year in advance. Adoption of these clocks should accelerate the identification of longevity genes and aging interventions.
NAD+ is required not only for life but for a long life. In this issue, Camacho-Pereira et al. (2016) implicate CD38 in the decline of NAD+ during aging, with implications for combating age-related ...diseases.
NAD+ is required not only for life but for a long life. In this issue, Camacho-Pereira et al. implicate CD38 in the decline of NAD+ during aging, with implications for combating age-related diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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