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Orchestrated apoptosis in planarian Dugesia japonica is very important for its degrowth and regeneration. Apoptosis Inhibitor-5 (API5) is an anti-apoptotic factor that negatively regulates cell apoptosis. We characterized the conserved structure of DjApi5, however, the biological function of DjApi5 in planarians needs further investigation. In this study, we found that DjApi5 and its interacting molecular DjAcinus are required for planarian homeostasis, which may be correlated with their specific localization in neoblasts in addition to their anti-apoptosis functions. We further demonstrated the increased expression of DjApi5 during planarian regeneration, and DjApi5 deficiency affects normal regeneration processes. These results indicated new functions of DjApi5 in development.

Abstract: Post-translational modifications (PTMs) of proteins influence protein degradation, protein- protein interactions, expression of genes, and intracellular signal transduction, thereby regulating major life processes. Among the PTMs occurring within the cytoplasm and nucleus, the most commonly studied one is the arginine methylation of proteins catalyzed by PRMTs. PRMT1 is the most excellent and extensively studied member of the PRMT family. PRMT1 occurs in various isoforms, and the unique sequence splicing of each of these isoforms encodes differential proteins that exhibit different cellular localization, substrate specificity, and enzyme activity. In addition to methylating histones, PRMT1 also methylates a large number of non-histone substrates that regulate a broad range of cellular processes. In recent years, research has revealed an increasing number of pathological diseases caused by the misregulation and aberrant expression of PRMT1, demonstrating the potential of PRMT1 as an effective biomarker for drug targets. In this context, the present study discusses the structural characteristics and the biological functions of PRMT1. Practical applications: Several diseases originate from aberrant post-translational modifications. The misregulation of the arginine methylation of proteins, which is regulated by PRMTs and influences a series of cellular activities, leads to developmental abnormalities and physiological diseases. PRMT1, which accounts for 85% of the activity of PRMTs, is involved in several cellular processes occurring in various diseases. Multiple inhibitors have been developed and studied for their potential as biomarkers and suitable drug targets in clinical application. The present report summarizes the findings of the most recent studies focusing on the structural characteristics, splicing, substrates, and biological functions of PRMT1, to contribute to future research for deciphering the molecular mechanisms of PRMT1 and drug improvement.

Background This study aimed to explore the molecular mechanisms of tibolone treatment in postmenopausal women. Methods The gene set enrichment profile, GSE12446, which includes 9 human endometrial samples from postmenopausal women treated with tibolone (tibolone group) and 9 control samples (control group), was downloaded from GEO database for analysis. Differentially expressed genes (DEGs) in tibolone vs. control groups were identified and then used for function and pathway enrichment analysis. Protein–protein interaction (PPI) network and module analyses were also performed. Finally, drug–target interaction was predicted for genes in modules, and then were validated in Pubmed. Results A total of 238 up-regulated DEGs and 72 down-regulated DEGs were identified. These DEGs were mainly enriched in various biological processed and pathways, such as cilium movement (e.g., CCDC114 and DNAI2), calcium ion homeostasis, regulation of hormone levels and complement/coagulation cascades. PPI network contained 368 interactions and 166 genes, of which IGF1, DNALI1, CCDC114, TOP2A, DNAH5 and DNAI2 were the hue genes. A total of 96 drug–gene interactions were obtained, including 94 drugs and eight genes. TOP2A and HTR2B were found to be targets of 28 drugs and 38 drugs, respectively. Among the 94 obtained drugs, only 12 drugs were reported in studies, of which 7 drugs (e.g., epirubicin) were found to target TOP2A. Conclusions CCDC114 and DNAI2 might play important roles in tibolone-treated postmenopausal women via cilium movement function. TOP2A might be a crucial target of tibolone in endometrium of postmenopausal women.

The engineering of supramolecular architectures needs accurate descriptions of the intermolecular interactions in crystal structures. Tetrathiafulvalene (TTF) is an effective building block used in the construction of promising functional materials. The parallel packing of the neutral TTF–TTF system was studied previously using the high-level quantum chemical method, advancing it as a valuable model system. The recently developed tight-binding quantum chemical method GFN2-xTB and local coupled-cluster method DLPNO-CCSD(T) were used to investigate the stacking interactions of TTF and selected derivatives deposited in the Cambridge Structural Database. Using the interaction energy of the TTF–TTF dimer calculated at the CCSD(T)/CBS level as the reference, the accuracies of the two methods are investigated. The energy decomposition analysis within the DLPNO-CCSD(T) framework reveals the importance of dispersion interaction in the TTF-related stacking systems. The dispersion interaction density plot vividly shows the magnitude and distribution of the dispersion interaction, providing a revealing insight into the stacking interactions in crystal structures. The results show that the GFN2-xTB and DLPNO-CCSD(T) methods could achieve accuracy at an affordable computational cost, which would be valuable in understanding the nature of parallel stacking in supramolecular systems.

Cerium oxide nanoparticles (n-CeO

The interaction between a tumor and the tumor microenvironment (TME) plays a key role in tumorigenesis and tumor progression. Ubiquitination, a crucial post‑translational modification for regulating protein degradation and turnover, plays a role in regulating the crosstalk between a tumor and the TME. Thus, identifying the roles of ubiquitination in the process may assist researchers to investigate the mechanisms underlying tumorigenesis and tumor progression. In the present review article, new insights into the substrates for ubiquitination that are involved in the regulation of hypoxic environments, angiogenesis, chronic inflammation‑mediated tumor formation, and the function of cancer‑associated fibroblasts and infiltrating immune cells (tumor‑associated macrophages, T‑cells, myeloid‑derived suppressor cells, dendritic cells, and natural killer cells) are summarized. In addition, the potential targets of the ubiquitination proteasome system within the TME for cancer therapy and their therapeutic effects are reviewed and discussed.

Background Planarians reliably regenerate all body parts after injury, including a fully functional head and central nervous system. But until now, the expression dynamics and functional role of miRNAs and other small RNAs during the process of head regeneration are not well understood. Furthermore, little is known about the evolutionary conservation of the relevant small RNAs pathways, rendering it difficult to assess whether insights from planarians will apply to other taxa. Results In this study, we applied high throughput sequencing to identify miRNAs, tRNA fragments and piRNAs that are dynamically expressed during head regeneration in Dugesia japonica. We further show that knockdown of selected small RNAs, including three novel Dugesia-specific miRNAs, during head regeneration induces severe defects including abnormally small-sized eyes, cyclopia and complete absence of eyes. Conclusions Our findings suggest that a complex pool of small RNAs takes part in the process of head regeneration in Dugesia japonica and provide novel insights into global small RNA expression profiles and expression changes in response to head amputation. Our study reveals the evolutionary conserved role of miR-124 and brings further promising candidate small RNAs into play that might unveil new avenues for inducing restorative programs in non-regenerative organisms via small RNA mimics based therapies.

Matrix Metalloproteinases (MMPs) belong to a family of metal-dependent endopeptidases which contain a series of conserved pro-peptide domains and catalytic domains. MMPs have been widely found in plants, animals, and microorganisms. MMPs are involved in regulating numerous physiological processes, pathological processes, and immune responses. In addition, MMPs play a key role in disease occurrence, including tumors, cardiovascular diseases, and other diseases. Compared with invertebrate MMPs, vertebrate MMPs have diverse subtypes and complex functions. Therefore, it is difficult to study the function of MMPs in vertebrates. However, it is relatively easy to study invertebrate MMPs because there are fewer subtypes of MMPs in invertebrates. In the present review, the structure and function of MMPs in invertebrates were summarized, which will provide a theoretical basis for investigating the regulatory mechanism of MMPs in invertebrates.

The growth and differentiation of neurons are critical events in the establishment of proper neuron connectivity and function. Planarians have a remarkable ability to completely regenerate a functional nervous system from a pluripotent stem cell population. Thus, planarians provide a powerful model to identify genes required for neuronal differentiation in vivo. The Wnt/Ca2+ signaling pathway is crucial for cancer development, arousing inflammatory responses, and neurodegeneration. We analyzed the expression patterns and RNAi phenotypes for members of the Wnt/Ca2+ signaling pathway in the planarian, Dugesia japonica. The expression of DjWnt5a, DjPLC-β, DjCamKII, and DjCaln during regeneration was surprisingly similar and revealing in the regenerated brain. RNAi knockdown of DjWnt5a, DjPLC-β, DjCamKII, and DjCaln led to defects in regenerated brains including brain partial deletions, incompact phenotypes at the posterior of the new brain, and lateral branches, which could not regenerate. Furthermore, the expressions of GAD and the number of GABAergic neurons decreased. Together, these results suggest that the Wnt/Ca2+ signaling pathway is required for GABAergic neuron regeneration.

The crystal structures of the antimicrobial drug tinidazole [TNZ; systematic name: 1-(2-ethylsulfonylethyl)-2-methyl-5-nitroimidazole, C8H13N3O4S] and the 1:1 cocrystal of TNZ with the naturally occurring compound vanillic acid (VA; systematic name: 4-hydroxy-3-methoxybenzoic acid, C8H8O4), namely, the TNZ–VA cocrystal, were determined by single-crystal X-ray analysis at 100 K. The supramolecular structure of the TNZ–VA cocrystal is composed of a carboxylic acid dimer and an O—H...N(heterocycle) synthon in the form of layers made up of O—H...N and O—H...O hydrogen bonds. The layers are joined via C—H...O hydrogen bonds, π–π stacking and C—H...π interactions. The energy framework analysis, together with interaction energy calculations using the DLPNO-CCSD(T) method, indicates that the TNZ–VA cocrystal inherits strong interactions from the TNZ and VA crystals, which accounts for the enhanced thermal stability and reduced dissolution rate. To the best of our knowledge, this is the first example of a cocrystal containing TNZ.

As a typical organism of platyhelminth, Dugesia japonica attracts more and more attention for its strong regenerative ability. Protein arginine methyltransferase (PRMT) family is composed of a class of enzymes with methyltransferase activities, which play fundamental roles in vivo in many important physiological processes. PRMT1 is a predominant type Ⅰ PRMT, which has been reported to be expressed in Schmidtea mediterranea. Nevertheless, the existence and the specific biological functions of PRMT1 in Dugesia japonica need further investigation. In this study, we acquired the full-length sequence of DjPRMT1 and confirmed it was a conserved protein. Thereafter, whole-mount in situ hybridization results showed DjPRMT1 was mainly expressed in neoblasts of adult worms, and obvious aggregation of DjPRMT1 was observed at the wound site in early stages of regeneration. Silencing of the DjPRMT1 gene retarded the movement of planarians with decreased DjPIWI-A expression, and DjPRMT1 knockdown also affected planarian regeneration with slightly attenuated proliferation around the blastema of posterior-facing wounds regeneration. In summary, these preliminary results demonstrated DjPRMT1 was involved in the regeneration of planarian.

Deoxyribonuclease II (DNase II) has been found to regulate inflammation, autoimmunity and apoptosis in vertebrates and invertebrates. The strong capacity of degrading DNA makes DNase II play an important role in the immune process. Planarian has become one of the model references due to its strong immune system, the environment they live makes planarians face the threat of microorganisms and injury, the strong immune system can protect planarians from the threat of bacterial and infection. In this study, we found that there was DNase in the lysis buffer of planarians, then we acquired the sequence of DjDN2s (Dugesia japonica DNase2s) and confirmed the DjDN2s were conserved DNase IIs. The predicted structure showed the active sites and binding patterns of DjDN2s. Whole-mount in situ hybridization results showed DjDN2s mainly expressed in immune organs. Quantitative real-time PCR revealed that the expression of DjDN2s upregulated in varying degrees when got hurt and challenged with bacteria, and the knockdown of DjDN2s led to the slower repair of wound. The recombinant phages which take DjDN2 also had the ability to degrade DNA and clear young biofilm of Gram-negative bacteria. Collectively, DNase II of planarian might play a role in the antimicrobial response and wound-induced response.

Freshwater planarian Dugesia japonica is an excellent model organism for investigating stem cell behavior during regeneration. Despite studies showing that numerous genetic factors are involved in regeneration, much more research is required to fully understand the molecular mechanisms that orchestrate regeneration. In this study, we identified an evolutionarily conserved gene DjPtpn11(DjShp2). DjPtpn11 transcripts are expressed in neoblasts and some differentiated cells, with a high expression at the newly formed blastema. Its silencing by RNA interference (RNAi) affected anterior regeneration and inhibited the regeneration of posterior regions, including cholinergic and serotonergic neuron regeneration. In adult planarians, DjPtpn11 knockdown did not affect neoblast survival and proliferation but might prevent the stem cell migration and differentiation through ERK signaling. DjPtpn11 was demonstrated to be necessary for the anterior blastema cell differentiation partially via regulating ERK-DjMkpA activity. DjPtpn11 also influenced posterior specification via DjIslet, suggesting that DjPtpn11 may be involved in regulating the Wnt signaling pathway during the development of posterior blastema. Together, these data identified that DjPtpn11 is an essential modulator for the regeneration of planarians, and it may influence the appropriate differentiation of blastema cells.

The last two decades have witnessed a rising interest in modulating the physicochemical properties of active pharmaceutical ingredients (APIs) through cocrystallization. The present study reports a new cocrystal of antimicrobial drug metronidazole (MNZ) using pyrogallol (PYR) as a cocrystal former, namely the MNZ–PYR cocrystal. The crystal structure of the MNZ–PYR cocrystal is studied by means of single-crystal X-ray diffraction, infrared spectroscopy, thermal analysis, and density functional theory calculations. The MNZ–PYR cocrystal shows an increased dissolution rate compared to MNZ due to the high energy conformer of PYR in the crystal lattice of the cocrystal. The formation of the MNZ–PYR cocrystal leads to a color shift from white (raw MNZ and PYR) to yellow, which is characterized by UV-vis spectroscopy and interpreted theoretically by means of time-dependent density functional theory calculations. The results suggest that the cocrystal strategy may be used for color tuning of APIs, offering opportunities for formulation development.

Pharmaceutical cocrystal as an alternative modification strategy presents opportunities for the formulation development of drugs with undesirable pharmacokinetic properties. Metronidazole (MNZ) is a water-soluble antimicrobial drug that can cause high plasma concentration peaks after administration, which may relate to serious encephalopathy. In the present study, the properties of MNZ were optimized through a cocrystallization strategy. A cocrystal of MNZ is prepared using gallic acid (GA) as cocrystal former. The structure of the prepared MNZ–GA cocrystal is studied by means of molecular dynamics and density functional theory calculations, powder X-ray diffraction, infrared spectroscopy, and thermal analysis. Comparative studies on the dissolution and absorption behaviors of raw MNZ and MNZ–GA cocrystal are completed. The results show that the MNZ–GA cocrystal exhibits lower Cmax and longer Tmax than pure metronidazole, suggesting that the prepared MNZ–GA cocrystal may find application in the formulation of MNZ.

In this study, the mechanism that VC inhibits lipid deposition through GSK-3β/mTOR signaling was investigated in the liver of Danio rerio. The results indicated that 0.5- and 1.0-g/kg VC treatments activated mTOR signaling by inhibiting GSK-3β expression. The mRNA expression of FAS, ACC, and ACL, as well as the content of TG, TC, and NEFA, was decreased by 0.5- and 1.0-g/kg VC treatments. Moreover, to confirm GSK-3β playing a key role in regulating TSC2 and mTOR, GSK-3β RNA was interfered and the activity of GSK-3β was inhibited by 25- and 50-mg/L LiCl treatments, respectively. The results indicated that GSK-3β inactivation played a significant role in inducing mTOR signaling and inhibiting lipid deposition. VC treatments could induce mTOR signaling by inhibiting GSK-3β, and mTOR further participated in regulating lipid deposition by controlling lipid profile in the liver of zebrafish.

The central pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) synchronizes peripheral oscillators to coordinate physiological and behavioural activities throughout the body. How circadian phase coherence between the SCN and the periphery is controlled is not well understood. Here, we identify hepatic SIRT7 as an early responsive element to light that ensures circadian phase coherence in the mouse liver. The SCN-driven body temperature (BT) oscillation induces rhythmic expression of HSP70, which promotes SIRT7 ubiquitination and proteasomal degradation. Acute temperature challenge dampens the BT oscillation and causes an advanced liver circadian phase. Further, hepatic SIRT7 deacetylates CRY1, promotes its FBXL3-mediated degradation and regulates the hepatic clock and glucose homeostasis. Loss of Sirt7 in mice leads to an advanced liver circadian phase and rapid entrainment of the hepatic clock upon daytime-restricted feeding. These data identify a BT-HSP70-SIRT7-CRY1 axis that couples the mouse hepatic clock to the central pacemaker and ensures circadian phase coherence and glucose homeostasis.

Retinoic acid-inducible gene I (RIG-I), an RNA sensor with a conserved structure, activates the host interferon (IFN) system to produce IFNs and cytokines for eliminating pathogens upon recognizing PAMPs. However, the biological functions and the mechanism by which RIG-I regulates the innate immunity response in invertebrates are still unknown at present. Here we identified an atypical RIG-I in planarian Dugesia japonica. Sequence analysis, 3D structure modeling and phylogenetic analysis showed that this atypical protein was clustered into a single clade at the base of the tree in invertebrates, suggesting that DjRIG-I is an ancient and unique protein of the RIG-I-like receptors (RLRs). In situ hybridization analysis revealed that the DjRIG-I mRNAs were predominantly expressed in the pharynx and head of the adult and regenerative planarians. Stimulation with PAMPs induced the over-expression of DjRIG-I in planarians. The molecular simulation demonstrated that DjRIG-I formed a large hole-structure for the docking of dsRNAs, and the pull-down assay confirmed the interaction between DjRIG-I and viral analog poly(I:C). Importantly, some representative antiviral/antibacterial genes in the RIG-I-mediated IFN and P38 signaling pathway, TBK1, IRF-3, Mx, and P38, were significantly upregulated in planarians stimulated with PAMPs. Interference of the DjRIG-I expression by RNAi, inhibited the PAMPs-induced over-expression, suggesting that DjRIG-I is a key player for downstream signaling events. These results indicate that DjRIG-I triggered the intracellular signaling cascades independent of the classical CARD domains and played an essential role in the virus/bacteria-induced innate immunity of planarian.

The T7 phage is a virulent phage hosted by Escherichia coli, which poses no threat to animals and plants. Due to the advantages of small genome, well elucidated functional genomics, fast life cycle, and high stability, T7 phage has been widely used in many fields, including biology and medicine. In this review, we focus on the research of T7 phages in biological sciences and medicine, including the application of T7 phages and T7 phage products, T7 phage display systems, and recombinant T7 phages in the treatment and diagnosis of infectious diseases (bacteria, viruses, parasites) and tumor diseases. In addition, we also introduce the therapeutic application of T7 phage in various diseases such as allergic reaction, Alzheimer's disease, inflammatory reaction, and other diseases, and finally discuss the future direction of T7 phage application in the biomedical field.

β-thymosin 4 (Tβ4) is a prototypical actin-monomer sequestering protein that plays an important role in mammalian cells and tissues. In vertebrates, Tβ4 is involved in various physiological and pathophysiological processes, such as angiogenesis, hair follicle and hair regeneration, nervous system development, inflammatory response, wound healing, tumour metastasis, and liver and heart protection. Additionally, thymosin domain-containing protein was discovered in invertebrates and was recently shown to be more homologous to Tβ4. However, the structural and functional properties are more complex and diverse than those of Tβ4. In this review article, we will discuss in detail the structural and functional aspects of β-thymosin in invertebrates.

This paper investigates the effect of lanthanum (La) on lipid deposition and Wnt10b signaling in the liver of male zebrafish with exposure of 0, 10, 20, and 30 μmol/L La. It suggests that La can be accumulated in liver, and its treatments decrease the activities and gene expression of enzymes related to fatty acid synthesis. The levels of total cholesterol (TC), triglyceride (TG), and nonesterified fatty acids (NEFA) as well as the size of lipid droplets are decreased by La treatments. Moreover, La treatments affect the composition of fatty acids and the content of nutrient elements. Meanwhile, they also induce the gene expression of wnt10b, β-catenin, pparα, and pparγ, but inhibit gsk-3β gene expression in liver. Further study on the result of wnt10b gene interference shows that Wnt10b/β-catenin signaling plays a crucial role in the regulatory process of hepatic lipid deposition. Taken together, our observations suggest that La accumulation affects lipid deposition in the liver of male zebrafish, and Wnt10b signaling pathway may be involved in this process.

Additional file 1: Supplemental_Data_S1. The reference sequences for mRNAs (including UTRs).

Apoptosis, also named programmed cell death, is a highly conserved physiological mechanism. Apoptosis plays crucial roles in many life processes, such as tissue development, organ formation, homeostasis maintenance, resistance against external aggression, and immune responses. Apoptosis is regulated by many genes, among which Apoptosis Inhibitor-5 (API5) is an effective inhibitor, though the structure of API5 is completely different from the other known Inhibitors of Apoptosis Proteins (IAPs). Due to its high expression in many types of tumors, API5 has received extensive attention, and may be an effective target for cancer treatment. In order to comprehensively and systematically understand the biological roles of API5, we summarized the evolution and structure of API5 and its roles in anti-apoptosis in this review.

A rotor-based probe MRMP-1 was designed and synthesized. MRMP-1 can bind to plasma membranes very quickly and stably with remarkable fluorescence enhancement. It can be used to monitor the dynamic changes in cell membranes in real-time under stimuli conditions. Importantly, MRMP-1 is the first rotor-based fluorescent sensor to label exosomes in living cells.

The DNA damage response (DDR) is a highly orchestrated process but how double-strand DNA breaks (DSBs) are initially recognized is unclear. Here, we show that polymerized SIRT6 deacetylase recognizes DSBs and potentiates the DDR in human and mouse cells. First, SIRT1 deacetylates SIRT6 at residue K33, which is important for SIRT6 polymerization and mobilization toward DSBs. Then, K33-deacetylated SIRT6 anchors to γH2AX, allowing its retention on and subsequent remodeling of local chromatin. We show that a K33R mutation that mimics hypoacetylated SIRT6 can rescue defective DNA repair as a result of SIRT1 deficiency in cultured cells. These data highlight the synergistic action between SIRTs in the spatiotemporal regulation of the DDR and DNA repair in humans and mice.

The tumor necrosis factor (TNF) superfamily consists of a wide variety of inflammatory cytokine, including cell-bound and secreted proteins. These TNFs function through binding and activation of the TNF receptors for modulating TNF-associated intracellular signals. A set of mammalian TNF receptor-associated factors (TRAFs) that have emerged as the major signal transducers for the TNF receptor superfamily, play an important role in both adaptive and innate immunity. However, the existence of TRAFs and their biological functions in planarian are still unknown. In this study, a new member of TRAFs, DjTRAF2, was identified in planarian Dugesia japonica. Phylogenetic analysis revealed that DjTRAF2 could be a new member of the invertebrate TRAF2 family. Sequence analysis showed that the open reading frame of DjTRAF2 had 1353 bp in length and encoded a putative protein of 450 amino acids with a predicted molecular mass of ~51.8 kDa and an isoelectric point of 7.052. Whole-mount in situ hybridization showed that DjTRAF2 was predominantly expressed in adult and regenerative pharynx, which is an important immune organ of planarian. Quantitative real-time PCR revealed that the transcriptional level of DjTRAF2 was significantly up-regulated after induced by pathogen-associated molecular patterns (polyinosinic-polycytidylic acid, lipopolysaccharide, peptidoglycan and β-glucan), suggesting that DjTRAF2 is involved in the immune response against pathogen invasion. Collectively, these results demonstrated that DjTRAF2 might play important roles in the innate immunity of planarian.

SummaryThe DNA damage response (DDR) is a highly orchestrated process but how double-strand DNA breaks (DSBs) are initially recognized is unclear. Here, we show that polymerized SIRT6 deacetylase recognizes DSBs and potentiates the DDR. First, SIRT1 deacetylates SIRT6 at residue K33, which is important for SIRT6 polymerization and mobilization toward DSBs. Then, K33-deacetylated SIRT6 anchors to γH2AX, allowing its retention on and subsequent remodeling of local chromatin. We show that a K33R mutation that mimics hypoacetylated SIRT6 can rescue defective DNA repair as a result of SIRT1 deficiency in cultured cells. These data highlight the synergistic action between SIRTs in the spatiotemporal regulation of the DDR and DNA repair.

Aged blood vessels accelerate systemic aging; SIRT7 gene therapy rejuvenates blood vessels and promotes longevity in aging model., Vascular dysfunction is a typical characteristic of aging, but its contributing roles to systemic aging and the therapeutic potential are lacking experimental evidence. Here, we generated a knock-in mouse model with the causative Hutchinson-Gilford progeria syndrome (HGPS) LmnaG609G mutation, called progerin. The Lmnaf/f;TC mice with progerin expression induced by Tie2-Cre exhibit defective microvasculature and neovascularization, accelerated aging, and shortened life span. Single-cell transcriptomic analysis of murine lung endothelial cells revealed a substantial up-regulation of inflammatory response. Molecularly, progerin interacts and destabilizes deacylase Sirt7; ectopic expression of Sirt7 alleviates the inflammatory response caused by progerin in endothelial cells. Vascular endothelium–targeted Sirt7 gene therapy, driven by an ICAM2 promoter, improves neovascularization, ameliorates aging features, and extends life span in Lmnaf/f;TC mice. These data support endothelial dysfunction as a primary trigger of systemic aging and highlight gene therapy as a potential strategy for the clinical treatment of HGPS and age-related vascular dysfunction.