SIRT7: the seventh key to unlocking the mystery of aging.

Aging is a chronic yet natural physiological decline of the body. Throughout life, humans are continuously exposed to a variety of exogenous and endogenous stresses, which engender various counteractive responses at the cellular, tissue, organ, as well as organismal levels. The compromised cellular and tissue functions that occur because of genetic factors or prolonged stress (or even the stress response) may accelerate aging. Over the last two decades, the sirtuin (SIRT) family of lysine deacylases has emerged as a key regulator of longevity in a variety of organisms. SIRT7, the most recently identified member of the SIRTs, maintains physiological homeostasis and provides protection against aging by functioning as a watchdog of genomic integrity, a dynamic sensor and modulator of stresses. SIRT7 decline disrupts metabolic homeostasis, accelerates aging, and increases the risk of age-related pathologies including cardiovascular and neurodegenerative diseases, pulmonary and renal disorders, inflammatory diseases, and cancer, etc. Here, we present SIRT7 as the seventh key to unlock the mystery of aging, and its specific manipulation holds great potential to ensure healthiness and longevity.

Near-infrared light controlled protein degradation by photo-caged lenalidomide and pomalidomide.

Immunomodulatory drugs (e.g. thalidomide, lenalidomide and pomalidomide) have been proven highly successful in clinical treatment of multiple myeloma. However, systematic degradation of zinc finger transcriptional factors induced by these drugs could lead to severe systematic toxicity in patients. Previous reports of NVOC caged pomalidomide attempted to regulate its activity using UVA irradiation, but their application was limited by high cytotoxicity and low tissue penetration. Here, we reported red-shifted BODIPY caged lenalidomide and pomalidomide that enabled red-light controlled protein degradation with spatiotemporal precision.

Evolution and Function of the Notch Signaling Pathway: An Invertebrate Perspective.

The highly conserved Notch signaling pathway affects embryonic development, neurogenesis, homeostasis, tissue repair, immunity, and numerous other essential processes. Although previous studies have demonstrated the location and function of the core components of Notch signaling in various animal phyla, a more comprehensive summary of the Notch core components in lower organisms is still required. In this review, we objectively summarize the molecular features of the Notch signaling pathway constituents, their current expression profiles, and their functions in invertebrates, with emphasis on their effects on neurogenesis and regeneration. We also analyze the evolution and other facets of Notch signaling and hope that the contents of this review will be useful to interested researchers.

Graphene-Based Hybrid Fillers for Rubber Composites.

Graphene and its derivatives have been confirmed to be among the best fillers for rubber due to their excellent properties, such as high mechanical strength, improved interface interaction, and strain-induced crystallization capabilities. Graphene rubber materials can be widely used in tires, shoes, high-barrier conductive seals, electromagnetic shielding seals, shock absorbers, etc. In order to reduce the graphene loading and endow more desirable functions to rubber materials, graphene-based hybrid fillers are extensively employed, which can effectively enhance the performance of rubber composites. This review briefly summarizes the recent research on rubber composites with graphene-based hybrid fillers consisting of carbon black, silica, carbon nanotubes, metal oxide, and one-dimensional nanowires. The preparation methods, performance improvements, and applications of different graphene-based hybrid fillers/rubber composites have been investigated. This study also focuses on methods that can ensure the effectiveness of graphene hybrid fillers in reinforcing rubber composites. Furthermore, the enhanced mechanism of graphene- and graphene derivative-based hybrid fillers in rubber composites is investigated to provide a foundation for future studies.

[Advances in live-imaging aging reporter mice].

Aging is an independent risk factor for chronic diseases in the elderly, and understanding aging mechanisms is one of the keys to achieve early prevention and effective intervention for the diseases. Aging process is dynamic and systemic, making it difficult for mechanistic study. With recent advances in aging biomarkers and development of live-imaging technologies, more and more reporter mouse models have been generated, which can live monitor the aging process, and help investigate aging mechanisms at systemic level and develop intervention strategies. This review summarizes recent advances in live-imaging aging reporter mouse models based on widely used aging biomarkers (p16Ink4a, p21Waf1/Cip1, p53 and Glb1), and discusses their applications in aging research.

High-Entropy Photothermal Materials.

High-entropy (HE) materials, celebrated for their extraordinary chemical and physical properties, have garnered increasing attention for their broad applications across diverse disciplines. The expansive compositional range of these materials allows for nuanced tuning of their properties and innovative structural designs. Recent advances have been centered on their versatile photothermal conversion capabilities, effective across the full solar spectrum (300-2500 nm). The HE effect, coupled with hysteresis diffusion, imparts these materials with desirable thermal and chemical stability. These attributes position HE materials as a revolutionary alternative to traditional photothermal materials, signifying a transformative shift in photothermal technology. This review delivers a comprehensive summary of the current state of knowledge regarding HE photothermal materials, emphasizing the intricate relationship between their compositions, structures, light-absorbing mechanisms, and optical properties. Furthermore, the review outlines the notable advances in HE photothermal materials, emphasizing their contributions to areas, such as solar water evaporation, personal thermal management, solar thermoelectric generation, catalysis, and biomedical applications. The review culminates in presenting a roadmap that outlines prospective directions for future research in this burgeoning field, and also outlines fruitful ways to develop advanced HE photothermal materials and to expand their promising applications.

Enhanced properties of gelatin films incorporated with TiO2-loaded reduced graphene oxide aerogel microspheres for active food packaging applications.

The synergistic effect of graphene sheets and titanium dioxide nanoparticles (TiO2) hybrid fillers can improve the antibacterial, mechanical, and barrier properties of gelatin (GL), making it more suitable to be used in the food packaging application. However, the uneven dispersion and aggregation of the hybrid fillers restrict its performance for further application. In order to achieve the above superior properties, reduced graphene oxide aerogel microspheres (rGOAMs) loaded with TiO2 (rGOAMs@TiO2) were successfully prepared using one-step hydrothermal process by reducing titanium sulfate into TiO2 on the framework of rGOAMs, followed by effective dispersion in the GL matrix to form nanocomposites (rGOAMs@TiO2/GL) through simultaneous ultrasonication and mechanical stirring, as well as an ultrasonic cell grinder process. Incorporating a mere 0.8 wt% of rGOAMs@TiO2 effectively improved the mechanical, antibacterial, UV light barrier, thermal stability, hydrophobicity, and water vapor barrier properties of the GL. Compared with the composites made of rGOAMs, TiO2, and GL (rGOAMs/TiO2/GL), rGOAMs@TiO2/GL composites showed stronger filler-matrix interactions, better filler dispersion, and lower TiO2 particle aggregation, suggesting superiority compared to rGOAMs/TiO2/GL composites at the same filler content. This innovative method of mixing GL with rGOAMs@TiO2 holds great promise for enhancing the suitability of GL in active food packaging applications.

Doxycycline decelerates aging in progeria mice.

Beyond the antimicrobial activity, doxycycline (DOX) exhibits longevity-promoting effect in nematodes, while its effect on mammals is unclear. Here, we applied a mouse model of Hutchinson-Gilford progeria syndrome (HGPS), Zmpste24 knockout (KO) mice, and analyzed the antiaging effect of DOX. We found that the DOX treatment prolongs lifespan and ameliorates progeroid features of Zmpste24 KO mice, including the decline of body and tissue weight, exercise capacity and cortical bone density, and the shortened colon length. DOX treatment alleviates the abnormal nuclear envelope in multiple tissues, and attenuates cellular senescence and cell death of Zmpste24 KO and HGPS fibroblasts. DOX downregulates the level of proinflammatory IL6 in both serum and tissues. Moreover, the elevated α-tubulin (K40) acetylation mediated by NAT10 in progeria, is rescued by DOX treatment in the aorta tissues in Zmpste24 KO mice and fibroblasts. Collectively, our study uncovers that DOX can decelerate aging in progeria mice via counteracting IL6 expression and NAT10-mediated acetylation of α-tubulin.

Thioacetamide Additive Homogenizing Zn Deposition Revealed by In Situ Digital Holography for Advanced Zn Ion Batteries.

Zinc ion batteries are considered as potential energy storage devices due to their advantages of low-cost, high-safety, and high theoretical capacity. However, dendrite growth and chemical corrosion occurring on Zn anode limit their commercialization. These problems can be tackled through the optimization of the electrolyte. However, the screening of electrolyte additives using normal electrochemical methods is time-consuming and labor-intensive. Herein, a fast and simple method based on the digital holography is developed. It can realize the in situ monitoring of electrode/electrolyte interface and provide direct information concerning ion concentration evolution of the diffusion layer. It is effective and time-saving in estimating the homogeneity of the deposition layer and predicting the tendency of dendrite growth, thus able to value the applicability of electrolyte additives. The feasibility of this method is further validated by the forecast and evaluation of thioacetamide additive. Based on systematic characterization, it is proved that the introduction of thioacetamide can not only regulate the interficial ion flux to induce dendrite-free Zn deposition, but also construct adsorption molecule layers to inhibit side reactions of Zn anode. Being easy to operate, capable of in situ observation, and able to endure harsh conditions, digital holography method will be a promising approach for the interfacial investigation of other battery systems.

Targeting CK2 eliminates senescent cells and prolongs lifespan in Zmpste24-deficient mice.

Senescent cell clearance is emerging as a promising strategy for treating age-related diseases. Senolytics are small molecules that promote the clearance of senescent cells; however, senolytics are uncommon and their underlying mechanisms remain largely unknown. Here, we investigated whether genomic instability is a potential target for senolytic. We screened small-molecule kinase inhibitors involved in the DNA damage response (DDR) in Zmpste24-/- mouse embryonic fibroblasts, a progeroid model characterized with impaired DDR and DNA repair. 4,5,6,7-tetrabromo-2-azabenzamidazole (TBB), which specifically inhibits casein kinase 2 (CK2), was selected and discovered to preferentially trigger apoptosis in Zmpste24-/- cells. Mechanistically, inhibition of CK2 abolished the phosphorylation of heterochromatin protein 1α (HP1α), which retarded the dynamic HP1α dissociation from repressive histone mark H3K9me3 and its relocalization with γH2AX to DNA damage sites, suggesting that disrupting heterochromatin remodeling in the initiation of DDR accelerates apoptosis in senescent cells. Furthermore, feeding Zmpste24-deficient mice with TBB alleviated progeroid features and extended their lifespan. Our study identified TBB as a new class senolytic compound that can reduce age-related symptoms and prolong lifespan in progeroid mice.

HuR promotes triglyceride synthesis and intestinal fat absorption.

Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the underlying mechanisms remain to be further studied. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3' UTR of Dgat2 mRNA and intron 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3' UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption.

Endothelium-specific SIRT7 targeting ameliorates pulmonary hypertension through Krüpple-like factor 4 deacetylation.

AIMS: Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by a high mortality rate. Pulmonary arterial endothelium cells (PAECs) serve as a primary sensor of various environmental cues, such as shear stress and hypoxia, but PAEC dysfunction may trigger vascular remodelling during the onset of PH. This study aimed to illustrate the role of Sirtuin 7 (SIRT7) in endothelial dysfunction during PH and explore the potential therapeutic strategy for PH. METHODS AND RESULTS: SIRT7 levels were measured in human and murine experimental PH samples. Bioinformatic analysis, immunoprecipitation, and deacetylation assay were used to identify the association between SIRT7 and Krüpple-like factor 4 (KLF4), a key transcription factor essential for endothelial cell (EC) homeostasis. Sugen5416 + hypoxia (SuHx)-induced PH mouse models and cell cultures were used for the study of the therapeutic effect of SIRT7 for PH. SIRT7 level was significantly reduced in lung tissues and PAECs from PH patients and the SuHx-induced PH mouse model as compared with healthy controls. Pulmonary endothelium-specific depletion of Sirt7 increased right ventricular systolic pressure and exacerbated right ventricular hypertrophy in the SuHx-induced PH model. At the molecular level, we identified KLF4 as a downstream target of SIRT7, which deacetylated KLF4 at K228 and inhibited the ubiquitination-proteasome degradation. Thus, the SIRT7/KLF4 axis maintained PAEC homeostasis by regulating proliferation, migration, and tube formation. PAEC dysfunction was reversed by adeno-associated virus type 1 vector-mediated endothelial overexpression of Sirt7 or supplementation with nicotinamide adenine dinucleotide (NAD)+ intermediate nicotinamide riboside which activated Sirt7; both approaches successfully reversed PH phenotypes. CONCLUSION: The SIRT7/KLF4 axis ensures PAEC homeostasis, and pulmonary endothelium-specific SIRT7 targeting might constitute a PH therapeutic strategy.

A direction-selective cortico-brainstem pathway adaptively modulates innate behaviors.

Sensory cortices modulate innate behaviors through corticofugal projections targeting phylogenetically-old brainstem nuclei. However, the principles behind the functional connectivity of these projections remain poorly understood. Here, we show that in mice visual cortical neurons projecting to the optic-tract and dorsal-terminal nuclei (NOT-DTN) possess distinct response properties and anatomical connectivity, supporting the adaption of an essential innate eye movement, the optokinetic reflex (OKR). We find that these corticofugal neurons are enriched in specific visual areas, and they prefer temporo-nasal visual motion, matching the direction bias of downstream NOT-DTN neurons. Remarkably, continuous OKR stimulation selectively enhances the activity of these temporo-nasally biased cortical neurons, which can efficiently promote OKR plasticity. Lastly, we demonstrate that silencing downstream NOT-DTN neurons, which project specifically to the inferior olive-a key structure in oculomotor plasticity, impairs the cortical modulation of OKR and OKR plasticity. Our results unveil a direction-selective cortico-brainstem pathway that adaptively modulates innate behaviors.