Clinical efficacy of OS-01 peptide formulation in reducing the signs of periorbital skin aging.

Background: The aging of the skin, particularly around the periorbital region, is a complex process characterized by the accumulation of senescent cells, decreased collagen production, and reduced skin elasticity, leading to visible signs such as fine lines, wrinkles, and sagging.

Objective: This study investigates the efficacy of a novel topical formulation, OS-01 EYE, containing the senomorphic peptide, OS-01, along with other active ingredients, in improving the skin around the eyes.

Methods: A 12-week clinical study was conducted with 22 participants who applied OS-01 EYE twice daily.

Double-blind, vehicle-controlled clinical investigation of peptide OS-01 for skin rejuvenation.

Introduction: Senescent cells contribute to age-related tissue deterioration, including the skin, which plays important roles in overall health and social interactions. This study aimed to assess the effects of the senotherapeutic peptide, OS-01 (a.k.

Senotherapeutic peptide treatment reduces biological age and senescence burden in human skin models.

Cellular senescence is known to play a role in age-related skin function deterioration which potentially influences longevity. Here, a two-step phenotypic screening was performed to identify senotherapeutic peptides, leading to the identification of Peptide (Pep) 14. Pep 14 effectively decreased human dermal fibroblast senescence burden induced by Hutchinson-Gilford Progeria Syndrome (HGPS), chronological aging, ultraviolet-B radiation (UVB), and etoposide treatment, without inducing significant toxicity.

and toxicity assessment of the senotherapeutic Peptide 14.

Senotherapeutic molecules decrease cellular senescence burden, constituting promising approaches to combat the accumulation of senescent cells observed in chronological aging and age-related diseases. Numerous molecules have displayed senotherapeutic potential, but toxicity has been frequently observed. Recently, a new senotherapeutic compound, Peptide 14, was developed to modulate cellular senescence in the skin.

Sulfur Amino Acid Supplementation Abrogates Protective Effects of Caloric Restriction for Enhancing Bone Marrow Regrowth Following Ionizing Radiation.

Radiation therapy damages and depletes total bone marrow (BM) cellularity, compromising safety and limiting effective dosing. Aging also strains total BM and BM hematopoietic stem and progenitor cell (HSPC) renewal and function, resulting in multi-system defects. Interventions that preserve BM and BM HSPC homeostasis thus have potential clinical significance.

Neurovascular dysfunction and neuroinflammation in a Cockayne syndrome mouse model.

Cockayne syndrome (CS) is a rare, autosomal genetic disorder characterized by premature aging-like features, such as cachectic dwarfism, retinal atrophy, and progressive neurodegeneration. The molecular defect in CS lies in genes associated with the transcription-coupled branch of the nucleotide excision DNA repair (NER) pathway, though it is not yet clear how DNA repair deficiency leads to the multiorgan dysfunction symptoms of CS. In this work, we used a mouse model of severe CS with complete loss of NER (), which recapitulates several CS-related phenotypes, resulting in premature death of these mice at approximately 20 weeks of age.

Highly accurate skin-specific methylome analysis algorithm as a platform to screen and validate therapeutics for healthy aging.

Background: DNA methylation (DNAm) age constitutes a powerful tool to assess the molecular age and overall health status of biological samples. Recently, it has been shown that tissue-specific DNAm age predictors may present superior performance compared to the pan- or multi-tissue counterparts. The skin is the largest organ in the body and bears important roles, such as body temperature control, barrier function, and protection from external insults.

Dietary protein restriction reduces circulating VLDL triglyceride levels via CREBH-APOA5-dependent and -independent mechanisms.

Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Dietary interventions based on protein restriction (PR) reduce circulating triglycerides (TGs), but underlying mechanisms and clinical relevance remain unclear. Here, we show that 1 week of a protein-free diet without enforced calorie restriction significantly lowered circulating TGs in both lean and diet-induced obese mice.

Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and HS Production.

Angiogenesis, the formation of new blood vessels by endothelial cells (ECs), is an adaptive response to oxygen/nutrient deprivation orchestrated by vascular endothelial growth factor (VEGF) upon ischemia or exercise. Hypoxia is the best-understood trigger of VEGF expression via the transcription factor HIF1α. Nutrient deprivation is inseparable from hypoxia during ischemia, yet its role in angiogenesis is poorly characterized.

Instrumental conditioning for food reinforcement in the spontaneously hypertensive rat model of attention deficit hyperactivity disorder.

Background: The spontaneously hypertensive rat is thought to show good validity as a model of attention deficit hyperactivity disorder, in part because of impaired delayed reinforcement behaviour, corresponding to the dynamic developmental theory of the disorder. However, some previous studies may have been confounded use of fluid reward. Therefore, the objective of this study was to assess the spontaneously hypertensive rat and two comparison strains (Wistar and Wistar Kyoto) using a non-delayed food reinforcement paradigm in an attempt to advance knowledge of basic learnt behaviour in this strain, without potentially confounding reward sensitivity, which could impact on motivation to learn.

Increased oxidative phosphorylation in response to acute and chronic DNA damage.

Accumulation of DNA damage is intricately linked to aging, aging-related diseases and progeroid syndromes such as Cockayne syndrome (CS). Free radicals from endogenous oxidative energy metabolism can damage DNA, however the potential of acute or chronic DNA damage to modulate cellular and/or organismal energy metabolism remains largely unexplored. We modeled chronic endogenous genotoxic stress using a DNA repair-deficient mouse model of CS.

Hypothalamic-Pituitary Axis Regulates Hydrogen Sulfide Production.

Decreased growth hormone (GH) and thyroid hormone (TH) signaling are associated with longevity and metabolic fitness. The mechanisms underlying these benefits are poorly understood, but may overlap with those of dietary restriction (DR), which imparts similar benefits. Recently we discovered that hydrogen sulfide (HS) is increased upon DR and plays an essential role in mediating DR benefits across evolutionary boundaries.

Auditory responses in a rodent model of Attention Deficit Hyperactivity Disorder.

A central component of Attention Deficit Hyperactivity Disorder (ADHD) is increased distractibility in response to visual and auditory stimuli, which is linked to the superior colliculus (SC). Furthermore, there is now mounting evidence of altered collicular functioning in ADHD and it is proposed that a hyper-responsive SC could mediate symptoms of ADHD, including distractibility. In the present study we conducted a systematic characterisation of the intermediate and deep layers of the SC in the most commonly used and well-validated model of ADHD, the spontaneously hypertensive rat (SHR), building on prior work showing increased distractible behaviour in this strain using visual distractors.

Nano-in-Micro Self-Reporting Hydrogel Constructs.

Highly reproducible Nano-in-Micro constructs are fabricated to provide a well-defined and self-reporting biomimetic environment for hepatocytes. Based on a protein/hydrogel formulation with controlled shape, size and composition, the constructs enable efficient nutrient exchange and provide an adhesive 3D framework to cells. Co-encapsulation of hepatocytes and ratiometric optical nanosensors with pH sensitivity in the physiological range allows continuous monitoring of the microenvironment.

Altered visual processing in a rodent model of Attention-Deficit Hyperactivity Disorder.

A central component of Attention-Deficit Hyperactivity Disorder (ADHD) is increased distractibility, which is linked to the superior colliculus (SC) in a range of species, including humans. Furthermore, there is now mounting evidence of altered collicular functioning in ADHD and it is proposed that a hyper-responsive SC could mediate the main symptoms of ADHD, including distractibility. In the present study we have provided a systematic characterization of the SC in the most commonly used and well-validated animal model of ADHD, the spontaneously hypertensive rat (SHR).

Endogenous hydrogen sulfide production is essential for dietary restriction benefits.

Dietary restriction (DR) without malnutrition encompasses numerous regimens with overlapping benefits including longevity and stress resistance, but unifying nutritional and molecular mechanisms remain elusive. In a mouse model of DR-mediated stress resistance, we found that sulfur amino acid (SAA) restriction increased expression of the transsulfuration pathway (TSP) enzyme cystathionine γ-lyase (CGL), resulting in increased hydrogen sulfide (H2S) production and protection from hepatic ischemia reperfusion injury. SAA supplementation, mTORC1 activation, or chemical/genetic CGL inhibition reduced H2S production and blocked DR-mediated stress resistance.

A novel electrospun biphasic scaffold provides optimal three-dimensional topography for in vitro co-culture of airway epithelial and fibroblast cells.

Conventional airway in vitro models focus upon the function of individual structural cells cultured in a two-dimensional monolayer, with limited three-dimensional (3D) models of the bronchial mucosa. Electrospinning offers an attractive method to produce defined, porous 3D matrices for cell culture. To investigate the effects of fibre diameter on airway epithelial and fibroblast cell growth and functionality, we manipulated the concentration and deposition rate of the non-degradable polymer polyethylene terephthalate to create fibres with diameters ranging from nanometre to micrometre.

Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction.

Mitochondrial dysfunction is a common feature in neurodegeneration and aging. We identify mitochondrial dysfunction in xeroderma pigmentosum group A (XPA), a nucleotide excision DNA repair disorder with severe neurodegeneration, in silico and in vivo. XPA-deficient cells show defective mitophagy with excessive cleavage of PINK1 and increased mitochondrial membrane potential.

Lifespan extension by dietary intervention in a mouse model of Cockayne syndrome uncouples early postnatal development from segmental progeria.

Cockayne syndrome (CS) is a rare autosomal recessive segmental progeria characterized by growth failure, lipodystrophy, neurological abnormalities, and photosensitivity, but without skin cancer predisposition. Cockayne syndrome life expectancy ranges from 5 to 16 years for the two most severe forms (types II and I, respectively). Mouse models of CS have thus far been of limited value due to either very mild phenotypes, or premature death during postnatal development prior to weaning.

Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer.

Unlabelled: While genomically targeted therapies have improved outcomes for patients with lung adenocarcinoma, little is known about the genomic alterations which drive squamous cell lung cancer. Sanger sequencing of the tyrosine kinome identified mutations in the DDR2 kinase gene in 3.8% of squamous cell lung cancers and cell lines.

Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion.

Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.

The Deinococcus radiodurans Snf2 intein caught in the act: detection of the Class 3 intein signature Block F branched intermediate.

Inteins are the protein equivalent of introns. They are remarkable and robust single turnover enzymes that splice out of precursor proteins during post-translational maturation of the host protein (extein). The Deinococcus radiodurans Snf2 intein is the second member of the recently discovered Class 3 subfamily of inteins to be characterized.

Splicing of the mycobacteriophage Bethlehem DnaB intein: identification of a new mechanistic class of inteins that contain an obligate block F nucleophile.

Inteins are single turnover enzymes that splice out of protein precursors during maturation of the host protein (extein). The Cys or Ser at the N terminus of most inteins initiates a four-step protein splicing reaction by forming a (thio)ester bond at the N-terminal splice junction. Several recently identified inteins cannot perform this acyl rearrangement because they do not begin with Cys, Thr, or Ser.