Aging-US

Waiting until the end of a subject’s lifespan is quite a leaden method of validating the efficacy of a longevity-based intervention. This method could take researchers generations upon generations to eventually validate an effective intervention—or—this method might not ever yield results seen by the general public. However, researchers may have devised an innovative way to solve this problem. “If we hope to control the aging process, we need to learn how to measure the rate of aging in shorter time periods.” Many researchers believe that measuring the rate of human aging can be done faster by using DNA methylation-based aging clocks. Methylation-based clocks are capable of determining human biological aging with impressive accuracy. Hypermethylated and demethylated regions of DNA (CpG islands near specific aging-associated genes) play key roles in turning certain genes on and off throughout the aging process. Therefore, methylation is an important biomarker of aging. While there is a short list of currently available biological aging clocks for researchers to use in studies of anti-aging therapies, the TruAge DNA methylation test is preferable in some cases, due to its accessibility, use of simple saliva samples and cost effectiveness. “For the first time, these biomarkers of aging give scientists the opportunity to study the effects of anti-aging compounds in real-time and directly in humans.” In a new study, researchers from TruMe Labs, National University of Singapore and Ponce de Leon Health used the TruAge DNA methylation test to validate Rejuvant®—a patent-pending anti-aging dietary supplement. The trial study yielded unprecedented results and the research paper authored by the team was published as the cover of Aging (Aging-US) Volume 13, Issue 22, entitled: “Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test”. Full blog - https://www.impactjournals.com/journals/blog/aging/trending-with-impact-aging-reduced-by-8-years-with-rejuvant/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203736 DOI - https://doi.org/10.18632/aging.203736 Full Text - https://www.aging-us.com/article/203736/text Correspondence to: Brian K. Kennedy email: bkennedy@nus.edu.sg and Yelena V. Budovskaya email: yelena@trumelabs.com Keywords: aging, DNA methylation, alpha-ketoglutarate (AKG), biologic age, Rejuvant About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at http://www.Aging-US.com​​ or connect with us on: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Aging-US published a Special Collection on Eye Disease which included "miR-106b suppresses pathological retinal angiogenesis" which reported that microRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. Here, the authors show that expression of the miR-106b-25 cluster is negatively regulated by the unfolded protein response pathway of protein kinase RNA-like ER kinase in a mouse model of neovascular AMD. They demonstrate that therapeutic delivery of miR-106b to the retina with lentiviral vectors protects against aberrant retinal angiogenesis in two distinct mouse models of pathological retinal neovascularization. Dr. Przemyslaw Sapieha and Dr. Vincent De Guire said, "Age-related macular degeneration (AMD) is a common [1] and complex [2, 3] disease of aging and the leading cause of irreversible loss of sight in elderly people." Early forms of AMD are characterized by subretinal lipoproteinaceous deposits, local attrition of photoreceptors and loss of visual sensitivity. Late forms of AMD are defined by geographic atrophy and/or pathologic choroidal neovascularization characterized by vascular sprouting from the choriocapillaris into the neural retina or subretinal space. Sustained reduction in retinal VEGF levels can lead to neurotoxicity and degeneration of RPE-choriocapillaris in mouse models. Importantly, assessment by fundus photography and fundus fluorescein angiography of patients on anti-VEGF therapy showed accelerated development of geographic atrophy. These findings justify the need for continued exploration of novel therapeutic interventions. Given that several inflammatory and growth factors in addition to VEGF are associated with the pathogenesis of NV AMD, a multi-targeted approach is warranted. The authors previously elucidated a specific miRNA signature in the vitreous and plasma of patients with NV AMD and observed a disease-associated increase in miR-146a and a decrease in miR-106b and miR-152. Interestingly, within this cohort, they found that both vitreous- and plasma-based miR-146a/miR-106b ratios had greater than 90% discriminatory power for classification of patients with NV AMD with an area under the receiver operating characteristic curve of 0,977 in vitreous humour and 0,915 in plasma, suggesting potential for a blood-based diagnostic. The Sapieha/De Guire Research Team concluded in their Aging-US Research Output that there are efforts to devise therapeutics that simultaneously inhibit several factors involved in retinal vascular disease given the clinical success of compounds such as Aflibercept. miRNAs regulate translation of multiple genes and hence may be considered as multi-target inhibitors. Their potential to mitigate retinal disease will grow as comprehensive landscapes of miRNAs in health and disease are established. Preclinical studies are underway for mimics or inhibition of specific miRNAs. Full Text - https://www.aging-us.com/article/202404/text Correspondence to: Przemyslaw Sapieha email: mike.sapieha@umontreal.ca and Vincent De Guire email: vdeguire.hmr@ssss.gouv.qc.ca Keywords: age related macular degeneration, miR-106b, PERK, choroidal neovascularization, angiogenesis About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM

Aging-US published a Special Collection on Eye Disease which included "ALKBH5-mediated m6A demethylation of FOXM1 mRNA promotes progression of uveal melanoma" which reported that ALKBH5, a key component of the N6-methyladenosine (m6A) methyltransferase complex, was significantly elevated in uveal melanoma cell lines and inhibited tumor growth in vitro and in vivo. EP300-induced H3K27 acetylation activation activated increased ALkbH5 expression and inhibited UM cell proliferation, migration, invasion and increased apoptosis in vitro. Besides, it may promote UM metastasis by inducing epithelial-to-mesenchymal transition (EMT) via demethylation of FOXM1 mRNA, which increases its expression and stability. It is a potential prognostic biomarker and therapeutic target in UM. Dr. Jingxiang Zhong and Dr. Lian Liu said, "Uveal melanoma (UM), which originates from melanocytes, is the most common primary intraocular malignancy in adults." Up to 50% of patients with primary malignant meningitis (UM) will develop metastatic disease. The most common sites of UM metastasis are the liver (60.5%), lungs (24.4%), skin/soft tissue (10.9%), and bone (8.4%). Unfortunately, the 1-year survival rate of UM patients with metastases is only 15% [5]. There is a pressing need to find useful prognostic biomarkers and therapeutic targets for this disease. Alkhabh5 overexpression of ALKBH5 promotes EMT of UM by upregulating FOXM1 expression via demethylating the m6A modification and further increasing the stability of FOXm1 mRNA. The Zhong/Liu Research Team concluded in their Aging-US Research Output, "we demonstrate that ALKBH5, which is positively regulated by epigenetic modifications of H3K27 acetylation, promotes tumor progression by inducing tumor EMT and increasing FOXM1 expression via m6A demethylation (Figure 7). Therefore, ALKBH5 is a potential target of UM molecular therapy." Full Text - https://www.aging-us.com/article/202371/text Correspondence to: Jingxiang Zhong email: tzjx@jnu.edu.cn and Lian Liu email: lianliu@jnu.edu.cn Keywords: uveal melanoma, ALKBH5, FOXM1, senescence-associated T cells, m6A demethylation About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM

For Aging’s Volume 11, Issue 18, the Journal devoted the Cover to a research paper by Dr. Alejandro Martin-Montalvo from the Department of Regeneration and Cell Therapy, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Sevilla, Spain Herein, the authors show, using wild-type and the Pax8 ablated model of hypothyroidism in mice, that hyperthyroidism and severe hypothyroidism are associated with an overall unhealthy status and shorter lifespan. Mild hypothyroid Pax8 +/- mice were heavier and displayed insulin resistance, hepatic steatosis and increased prevalence of liver cancer yet had normal lifespan. Dr. Martin-Montalvo said, "The increasing burden of age-related diseases highlights the importance of uncovering the mechanisms underlying the aging process." TSH stimulates the production of T4 and T3 in the thyroid gland, which in turn inhibit both TRH and TSH synthesis when THs reach the hypothalamus and hypophysis, respectively. Greater life expectancy has been associated with reduced circulating levels of T4, T3, and/or high TSH levels in both animal models and humans. In this line, the Laron, Ames and Snell dwarf mice, which have reduced GH signalling and reduced circulating TH levels, exhibit a consistent exceptional lifespan as well as other metabolic alterations such as enhanced hepatic insulin sensitivity. Both rodents and humans under calorie restriction, which comprises a variety of nutritional interventions with several beneficial effects including extended longevity, exhibit reduced circulating T3 levels and/or high TSH levels. Likewise, nonagenarians from families with exceptional long lifespans, as well as their descendants, have been reported to exhibit increased TSH levels and/or decreased circulating T3 levels. The Martin-Montalvo research team concluded, "In 1908 Dr. Max Rubner proposed the rate of living theory of aging and longevity, postulating that species with a low metabolic rate would have increased life expectancy when compared to species with a higher metabolic rate. In this line, restricted levels of THs, which control the metabolic rate, have been associated with increased longevity as well as metabolic fitness." Full Text - https://www.aging-us.com/article/102285/text Correspondence to: Alejandro Martin-Montalvo; email: alejandro.martinmontalvo@cabimer.es and Benoit Raymond Gauthier; email: benoit.gauthier@cabimer.es Keywords: lifespan, healthspan, thyroid hormones, hyperthyroidism, hypothyroidism, glucose metabolism About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. Please visit our website at http://www.Aging-US.com or connect with us on: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC

Aging-US published a Special Collection on Eye Disease which included "Age-related changes in eye lens biomechanics, morphology, refractive index and transparency" which reported that life-long eye lens function requires an appropriate gradient refractive index, biomechanical integrity and transparency. The authors conducted an extensive study of wild-type mouse lenses 1-30 months of age to define common age-related changes. Biomechanical testing and morphometrics revealed an increase in lens volume and stiffness with age. Their results suggest similarities between murine and primate lenses and provide a baseline for future lens aging studies. Dr. Velia M. Fowler and Dr. Catherine Cheng said, "The eye lens is required for fine focusing of light onto the retina to form a clear image, and the function of the lens is intimately tied to its shape, biomechanical properties, transparency and refractive index." The eye lens is required for fine focusing of light onto the retina to form a clear image. It has long been known that age-related changes in these lens properties lead to two major lens pathologies, cataracts and presbyopia. Presbyopia is caused by a reduction in the lens' ability to change shape during focusing (accommodation), and, by extension, the need for reading glasses. Mice offer an opportunity to investigate changes in lens morphometrics, stiffness, transparency and refractive properties with age in a relatively shortened period of time. Little is known about the morphological, mechanical, refractive and cellular changes that occur with advanced age in the lens. The authors demonstrate that age-related changes in mouse lenses mimic some aspects of aging in human lenses. The Fowler/Cheng Research Team concluded in their Aging-US Research Output, "the increases in lens size and nucleus size are correlated with increase stiffness with age. The addition of new fiber cells at the lens periphery becomes disordered with age, but this does not appear to impact lens biomechanical properties. Cataracts in aged lenses can be due to cell structural abnormalities, including incomplete suture closure, collapse of the lens epithelial cell layer into the suture gap and loss of epithelial-fiber cell attachments and compaction of the cortical lens fiber cells forming a circumferential light scattering ring. GRIN is present in the lens from 2 weeks of age and continues to increase until about 6 months of age, after which the maximum refractive index remains stable. The increase in the area of highest refractive index at the center of the lens is directly correlated with the increase in lens nucleus size, suggesting nuclear compaction drives the maximum GRIN. Whether there is a common molecular mechanism that drives changes in all the measured parameters remains unknown, but further biochemical and cell morphology studies will be needed to determine how subcellular aging affects the whole tissue. Thus, our study provides a baseline for future studies of lens aging by providing quantitative measurements of key parameters and identifying common age-related changes in the overall tissue and in individual cells" Full Text - https://www.aging-us.com/article/102584/text Correspondence to: Velia M. Fowler email: vfowler@udel.edu and Catherine Cheng email: ckcheng@iu.edu Keywords: fiber cell, strain, epithelial cell, cataract, stiffness About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. Please visit our website at http://www.Aging-US.com

Aging-US published a Special Collection on Eye Disease which included "ALDH2 protects naturally aged mouse retina via inhibiting oxidative stress-related apoptosis and enhancing unfolded protein response in endoplasmic reticulum" which reported that during the process of aging, the retina exhibits chronic oxidative stress damage. These authors' preliminary experiment showed that acetaldehyde dehydrogenase 2 could alleviate retinal damage caused by OS. Retinal function and structure in vivo and in vitro were examined in aged ALDH2+ overexpression mice and ALDH2 agonist Alda1-treated aged mice. Levels of ALDH2, endoplasmic reticulum stress, apoptosis and inflammatory cytokines were evaluated. Moreover, aged ALDH2+ overexpression mice and aged Alda1-treated mice exhibited better retinal function and structure. Increased expression of glucose-regulated protein 78 and ERS-related protein phosphorylated eukaryotic initiation factor 2 and decreased expression of apoptosis-related protein, including C/EBP homologous protein, caspase12 and caspase9, and retinal inflammatory cytokines were detected in the retina of aged ALDH2+ overexpression mice and aged Alda1-treated mice. Dr. Tao Chen and Dr. Wei Ge said, "The aging process is characterized by a decline in systematic tissue function and the onset of serious of age-related disease." However, it remained elusive that the potential mechanisms accounting for these phenomena and strategies to intervene to improve cell functions. Recently, the imbalance of protein homeostasis was proposed to be responsible for aging and age-related diseases. Furthermore, eukaryotic translation initiation factor 2, a protein translation component, is the downstream of PERK. When endoplasmic reticulum stress happens, eIF2 is phosphorylated to slow down protein production and reduce the unfolded and misfolded proteins. Nevertheless, the underlying mechanisms of UPRER related to aged retinal behaviour remain largely unclear, and effective therapies to intervene in aging-related injury to the retina by targeting the UPRER have not been developed. Mitochondrial aldehyde dehydrogenase 2 is essential for the catabolism of exogenous and endogenous toxic aldehydes associated with oxidative stress-induced lipid peroxidation and adducts with DNA, RNA and protein. The Chen/Ge Research Team concluded in their Aging-US Research Output, "overexpression of ALDH2 and treatment with the ALDH2 agonist Alda1 in aging mice could both result in good retinal function and structural integrity via attenuating oxidative stress and apoptosis, and enhancing UPRER. Therefore, an increasing expression of ALDH2 could serve to preserve retinal function during the normal aging process or the onset of age-related retinal disease." Full Text - https://www.aging-us.com/article/202325/text Correspondence to: Tao Chen email: ct1988@fmmu.edu.cn and Wei Ge email: geweidr@fmmu.edu.cn Keywords: ALDH2, UPRER, retina, aged mice, oxidative stress About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM

Aging-US published a Special Collection on Eye Disease which included "Exosomes derived from BDNF-expressing 293T attenuate ischemic retinal injury in vitro and in vivo" which reported that this study investigated whether exosomes derived from BDNF-expressing 293T cells can be internalized by ischemic retinal cells and exert neuroprotective roles. The results demonstrated that 293T-Exo significantly attenuated the loss of cell proliferation and cell death in R28 cells in response to oxygen-glucose deprivation treatment. Mechanistic studies revealed that the endocytosis of 293T-Exo by R28 cells displayed dose- and temperature-dependent patterns and may be mediated by the caveolar endocytic pathway via the integrin receptor. Dr. Genlin Li and Dr. Yanling Wang said, "Retinal ischemia-reperfusion (I/R) emerges in many ocular diseases and is a leading cause of neuronal death and dysfunction, resulting in irreversible visual impairment or blindness." Growing reports demonstrated that retinal ischemia is a primary contributor to the pathogenesis of multiple diseases, such as retinal vascular occlusions, diabetic retinopathy, central retinal vein occlusion, as well as age-associated macular degeneration. Exosomes are synthesized and released by various cell types and transport active biological molecules to regulate the physiological activities of recipient cells. Thus, exosomes play an essential role in intercellular communication. Therefore, understanding the mechanism of exosome uptake would promote the development of more efficient delivery systems for disease treatment. Brain-derived neurotrophic factor, a member of the nerve growth factor gene family, is an essential multi-functional factor in various neuronal processes, including learning and memory, dendritic and synaptic plasticity, and axonal growth. The Li/Wang Research Team concluded in their Aging-US Research Output "the results suggest that 293T-Exo is endocytosed by retinal cells through the caveolar endocytic pathway via the integrin receptor. In addition, 293T-Exo exerts a neuroprotective role in the ischemic retina, both >in vitro and in vivo. The findings from the present study demonstrates a significant therapeutic potential of exosomes and provides an understanding of how to develop exosome-based therapies for retinal ischemia." Full Text - https://www.aging-us.com/article/202245/text Correspondence to: Genlin Li email: ligenlin2018@163.com and Yanling Wang email: wangyanling999@vip.sina.com Keywords: retinal ischemia, exosome, brain-derived neurotrophic factor, endocytosis, apoptosis About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM

Many aging-associated neurodegenerative disorders, including Alzheimer’s disease, involve the aggregation of abnormal tau in nerve cells (neurons). Normally, tau proteins function to stabilize microtubules in the brain. Tauopathy occurs when tau proteins become misfolded and misshapen (which turns tau into toxic tau). They then continue to proliferate and bind to each other, forming tau oligomers. These tau oligomers are more toxic and have a greater potential to spread tau pathology. Before toxic tau snowballs into neurodegenerative disorders, the events that lead up to abnormal tau have remained elusive to researchers. “While the association between tau levels and energy metabolism is established, it is not clear whether mitochondrial dysfunction is an early pathological feature of high levels of tau or a consequence of its excessive formation of protein aggregates.” Previous studies have demonstrated an association between tau levels and mitochondrial metabolism, however, determining which one proceeds the other has yet to be fully illuminated. Shedding light on this subject, researchers—from the University of Copenhagen, National and Kapodistrian University of Athens and the National Institutes of Health’s National Institute on Aging—used a Caenorhabditis elegans (C. elegans; roundworm/nematode) model of tau to examine mitochondrial changes over time. Their paper was chosen as the cover of Aging (Aging-US) Volume 13, Issue 21, published in November of 2021 and entitled, “Alteration of mitochondrial homeostasis is an early event in a C. elegans model of human tauopathy”. Full blog - https://www.impactjournals.com/journals/blog/aging/trending-with-impact-worms-reveal-early-event-in-neurodegeneration/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203683 DOI - https://doi.org/10.18632/aging.203683 Full Text - https://www.aging-us.com/article/203683/text Correspondence to: Konstantinos Palikaras email: palikarask@med.uoa.gr, Mansour Akbari email: akbari@sund.ku.dk and Vilhelm A. Bohr email: bohrv@grc.nia.nih.gov Keywords: aging, Alzheimer’s disease, C. elegans, energy metabolism, mitochondria, tau, tauopathy About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at http://www.Aging-US.com​​ or connect with us on: SoundCloud - https://soundcloud.com/aging-us​ Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ Pinterest - https://www.pinterest.com/AgingUS/ Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Aging-US published a Special Collection on Eye Disease which included "Suppressing endoplasmic reticulum stress-related autophagy attenuates retinal light injury" which reported that in this study, oxidative stress, endoplasmic reticulum stress and autophagy caused by light exposure were evaluated in vitro and in vivo. Additionally, inhibiting ER stress either by knocking down PERK signals or with GSK2606414 treatment remarkably suppressed prolonged autophagy and protected the cells against light injury. In vivo experiments verified neuroprotection via inhibiting ER stress-related autophagy in light-damaged retinas of mice. In conclusion, the above results suggest that light-induced photo-oxidative stress may trigger subsequent activation of ER stress and prolonged autophagy in photoreceptors and RPE cells. Suppressing ER stress may abrogate over-activated autophagy and protect the retina against light injury. Dr. Guang-Yu Li from The Second Hospital of Jilin University said, "Age-related macular degeneration (AMD) is a degenerative retinal disease, which often occurs in the elderly and causes irreversible loss of central vision." Indeed, excessive and prolonged light exposure may damage the retina and is an environmental factor that can accelerate AMD. With the rapid development of technology, many electronic devices with screens, and ophthalmic equipment with intensive illumination, have become widely used. Therefore, an increasing amount of attention has been focused on issues of light pollution and retinal light damage. Previous studies have shown that excessive intracellular ROS may lead to depletion of the GSH pool and compromise the function of PDI, which disrupts the folding process of proteins in the ER and produces a massive amount of misfolded proteins. However, the excessive accumulation of misfolded proteins in the ER may trigger an unfolded-protein response, which may enhance protein folding ability, as well as the homeostasis of protein translation and accelerate protein degradation to recover ER function. However, prolonged autophagy may lead to cell death and is specifically termed autophagy-dependent cell death. The role of autophagy in retinal light injury is controversial. Autophagy might be a double-edged sword among the molecular mechanisms that lead to retinal light damage. Midorikawa et al. reported that moderate autophagy combined with endosomal degradation pathway activity is neuroprotective and attenuates light-dependent retinal degeneration. The Li Research Team concluded in their Aging-US Research Output "the current study demonstrated that ER stress and autophagy are both involved in light-induced death of photoreceptors and RPE cells. As an upstream step, photo-oxidation may cause an imbalance in the cellular redox status and interrupt the folding process of proteins, further triggering ER stress in photoreceptors and RPEs. Suppressing ER stress via PERK signals may inhibit prolonged autophagy and protect photoreceptors/RPEs against light damage. Inhibiting ER stress-related autophagy is neuroprotective for retinal against light injury, which may be a potential treatment strategy for AMD." Full Text - https://www.aging-us.com/article/103846/text Correspondence to: Guang-Yu Li email: l_gy@jlu.edu.cn Keywords: oxidative stress, ER stress, autophagy, AMD, PERK

Aging-US published a Special Collection on Eye Disease which included "Development and validation of an immune and stromal prognostic signature in uveal melanoma to guide clinical therapy" which reported that the tumor microenvironment is known to play an important role in uveal melanoma. Reliable prognostic signatures are needed to aid high risk patients and improve prognosis. Immune and stromal scores were calculated by applying the "ESTIMATE" algorithm. The authors found that the median survival time of the low immune/stromal score group is longer than that of the high-score group. Dr. Liang Hu from The Wenzhou Medical University said, "Uveal melanoma (UM) is the most common type of malignant tumor of the adult eye, and 50% of patients with UM will eventually die as a result." Tumor microenvironment (TME) plays a pivotal role in cancer progression and therapeutic responses. Prognostic biomarkers related to TME may hold great promise in identifying molecular targets and guiding patient management. Immune and stromal cells are two major types suggested as crucial for the diagnostic and prognostic assessment of tumors. Scores can be calculated using the ESTIMATE algorithm to predict the infiltration of non-tumor cells in UM patients. The Hu Research Team concluded in their Aging-US Research Output, "our study reveals a comprehensive landscape of the immune and stromal microenvironment in UM, and provides a promising prognostic signature for UM. Patients with the high risk scores could benefit more from anti-PD-1 therapy and chemotherapy. Further investigations are needed to verify the accuracy in estimating prognoses and to test its clinical utility in patient management." Full Text - https://www.aging-us.com/article/103779/text Correspondence to: Liang Hu email: liang_hu@live.cn Keywords: uveal melanoma, immune, stromal, prognosis About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM