Aging-US

Aging-US published a Special Collection on Eye Disease which included "Nutraceutical effects of Emblica officinalis in age-related macular degeneration" which reported that EO has been used extensively as a nutraceutical in several diseases since it is known to boost immunity and offers numerous health benefits such as antioxidant, anti-inflammatory, and anti-aging effects. AMD RPE transmitochondrial cell lines were created by fusion of mitochondria DNA-deficient APRE-19 (Rho0) cells with platelets isolated from AMD patients. EO significantly improved live cell number and mitochondrial membrane potential, reduced apoptosis and oxidative stress, down-regulated VEGF, and up-regulated PGC-1α. Dr. M. Cristina Kenney from The University of California Irvine said, "Emblicaofficinalis Gaetrn (Phyllanthus emblica), commonly known as Indian gooseberry or Amla, is an edible fruit which is borne on a deciduous tree of the same name." All parts of the Emblicaofficinalis (EO) tree i.e, fruits, bark, leaves, seeds, flowers, and roots are known to have medicinal properties. EO is native to the tropical and subtropical regions of Southeast Asia including India, China, Malaysia, Bangladesh, Sri Lanka, and Mascarene Island. Phytochemically it is composed of several bioactive compounds such as flavonoids, phenolic compounds, tannins, amino acids, cellulose, gum, and albumin. It is well-known as an immunity boosting food due to its high Vitamin C content which on an average is ~600 mg/100 g. The Kenney Research Team concluded in their Aging-US Research Output, "treatment with purified EO extract preserves mitochondrial and cellular health and function in human AMD RPE cybrids, implying that EO mitigates aging-related damage in AMD. Since EO extract is an over-the-counter nutraceutical and is available in both liquid and capsule forms for easy consumption, it might serve as an effective, inexpensive, and non-invasive therapeutic option for treatment of AMD. Further studies are required to fully understand the precise mechanisms that orchestrate the protective events post EO treatment in AMD cells." Full Text - https://www.aging-us.com/article/101820/text Correspondence to: M. Cristina Kenney email: mkenney@uci.edu Keywords: Emblica officinalis, Phyllanthus emblica, Indian gooseberry, Amla, nutraceutical, age-related macular degeneration, AMD 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 "A comprehensive evaluation of 181 reported CHST6 variants in patients with macular corneal dystrophy" which reported that macular corneal dystrophy is an autosomal recessive disease featured by bilateral progressive stromal clouding and loss of vision, consequently necessitating corneal transplantation. In this study, the authors integrated all the reported CHST6 variants described in 408 MCD cases, and performed a comprehensive evaluation to better illustrate the causality of these variants. In addition, the results underscored the strong correlation between mutant frequency and residue conservation in the general population, thus providing potential candidate targets for further genetic manipulation. Dr. Jianjiang Xu from The Fudan University said, "Macular corneal dystrophy (MCD; OMIM 217800) is an autosomal recessive disease featured by bilateral progressive stromal clouding and loss of vision, finally necessitating corneal transplantation." The CHST6 gene spans approximate 23 kb of the short arm of chromosome 16 and consists of 4 exons and a 1,187 bp open reading frame. The encoded protein CHST6 contains 395 amino acids with a molecular weight of 44 kDa. Variants in CHST6 gene have been recognized as the most critical genetic components in MCD. To date, more than 100 frameshift, nonsense, or missense variants in CHST6 were described in patients with MCD I/IA. In MCD II patients, large rearrangements and deletions in the upstream of CHST6 were initially reported, followed by subsequent identification of mutations within the coding region of CHST6. However, substantial genetic heterogeneity still exists, and there is no study systematically evaluating CHST6 variants in MCD patients, in particular with regards to genotype-phenotype correlation and informing on the significance of specific variants. In the current study, the authors conducted a comprehensive evaluation of all 181 CHST6 variants described in MCD patients, and then classified the pathogenicity of those variants according to the American College of Medical Genetics and Genomics guidelines. The Xu Research Team concluded in their Aging-US Research Output, "the current comprehensive evaluation contributed to the most updated in-silico classification of all reported CHST6 variants till now. Although the vast majority of CHST6 variants are likely to be protein damaging, systematic functional investigations are still in urgent need to demonstrate the pathogenicity of these variants." Full Text - https://www.aging-us.com/article/101807/text Correspondence to: Jianjiang Xu email: jianjiangxu@126.com Keywords: CHST6, macular corneal dystrophy, genetic variants 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 "Effects of senescent secretory phenotype acquisition on human retinal pigment epithelial stem cells" which reported that loss of retinal pigment epithelium (RPE) cells occurs early in AMD, and their transplant has the potential to slow disease progression. Age-related MSC changes involve loss of function and acquisition of a senescence-associated secretory phenotype (SASP). These changes can contribute to the maintenance of a chronic state of low-grade inflammation in tissues and organs. Dr. Cesare Mariotti from The Università Politecnica delle Marche said, "Age-related macular degeneration (AMD) is an eye disorder affecting the elderly which can induce an irreversible loss of central visual function." Age-related macular degeneration (AMD) is one of the most serious and debilitating forms of aging-related eye disease. Smoking, cataract surgery, high BMI and cardiovascular disease are risk factors for AMD, as well as a family history of AMD. No effective treatment is available for neovascular AMD, while anti-VEGFD is the mainstay of treatment for dry AMD. Neovascular AMD and GA are characterized by RPE dysfunction; formation of large confluent drusen and hyperpigmentation seem to be the initial insult. AMD patients show a different phenotype as well as functional changes such as altered autophagy, mitochondrial dysfunction, and susceptibility to oxidative stress. A greater understanding of the molecular pathways that are involved in the various stages of AMD would contribute to the development of innovative therapies. The Mariotti Research Team concluded in their Aging-US Research Output that RPESCs can undergo replicative senescence, which affects their proliferation and differentiation ability. In addition, they acquired the SASP, which probably compounds the inflammatory RPE microenvironment during AMD development and progression. A greater understanding of the role of RPESCs in AMD pathogenesis is needed to find means to control the disease. Full Text - https://www.aging-us.com/article/101624/text Correspondence to: Cesare Mariotti email: mariottiocul@gmail.com Keywords: AMD, RPESCs, age-related diseases, senescence, inflammation 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

Compounding evidence from experimental, epidemiological and clinical studies indicate that cerebral amyloid plaque formation, vascular dysfunction and reduced cerebral blood flow (CBF) all play important roles in the cognitive decline associated with aging and aging-related diseases. Recently, hyperbaric oxygen therapy (HBOT) was shown to improve cognitive performance in animal models of Alzheimer’s disease (AD) and in human patients. However, previous research has not directly shown how, or if, HBOT mitigates cerebrovascular dysfunction in AD. “Therefore, we investigated the effects of HBOT on CBF and cognitive decline in the 5XFAD mouse model of AD that presents aggressive accumulation of amyloid load, cerebrovascular abnormalities and cognitive impairment, as well as in elderly individuals suffering from significant memory loss.” Researchers from Tel Aviv University and Shamir (Assaf Harofeh) Medical Center conducted a new research study in an effort to better understand the underlying mechanisms of HBOT-mediated effects. They authored a trending research paper, published by Aging (Aging-US) in August 2021, entitled, “Hyperbaric oxygen therapy alleviates vascular dysfunction and amyloid burden in an Alzheimer’s disease mouse model and in elderly patients.” Full blog - https://www.impactjournals.com/journals/blog/aging/trending-with-impact-new-hyperbaric-oxygen-hbot-study-breaks-ground/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203485 DOI - https://doi.org/10.18632/aging.203485 Full text - https://www.aging-us.com/article/203485/text Correspondence to: Uri Ashery email: uria@tauex.tau.ac.il Keywords: Alzheimer's disease, hyperbaric oxygen therapy, vascular dysfunction, cerebral blood flow, amyloid burden, aging 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: Twitter - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ SoundCloud - https://soundcloud.com/aging-us​ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ 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 "Long-term intake of Lactobacillus paracasei KW3110 prevents age-related chronic inflammation and retinal cell loss in physiologically aged mice" which reported that age-related chronic inflammation is a major risk factor for the incidence and prevalence of age-related diseases, including infectious and neurodegenerative diseases. These authors previously reported that Lactobacillus paracasei KW3110 activated macrophages and suppressed inflammation in mice and humans. In this study, they investigated whether long-term intake of heat-killed L. paracases altered the gut microbiota in physiologically aged mice. Compared with age-matched control mice, fecal analyses of gut microbiota revealed that intake of L.paracases KW 3110 mitigated age-related changes of beneficial bacterial composition, including the Bifidobacteriaceae family. Dr. Mitsuo Maruyama and Dr. Yuji Morita said, "Aging involves a progressive decline of physiological functions in various organs, influenced by several factors, including genetic factors and environmental factors." As the aged population grows, the therapeutic and preventive approaches to decelerate senescence are of great concern. The decline in immune function has been widely examined, because it results in chronic low grade inflammation. Age-related retinal neurodegenerative diseases, such as age-related macular degeneration, are major causes of blindness in the elderly. Disruption of gut microbiota composition has been also implicated in retinal diseases through a gut-retina axis. The Maruyama/Morita Research Team concluded in their Aging-US Research Output, "the intake of L. paracasei KW3110 mitigated chronic inflammation in the intestine and retina, and reduced age-related retinal cell death. Further studies are needed to evaluate the effects in age-related senescent changes of the retina." Full Text - https://www.aging-us.com/article/101583/text Correspondence to: Mitsuo Maruyama email: michan@ncgg.go.jp and Yuji Morita email: Yuji_Morita@kirin.co.jp Keywords: KW3110 Lactobacillus paracasei, age-related inflammation, proinflammatory cytokine, retina 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 "p62 /SQSTM1 coding plasmid prevents age related macular degeneration in a rat model" which reported that P62/SQSTM1, a multi-domain protein that regulates inflammation, apoptosis, and autophagy, has been linked to age-related pathologies. In retinal pigment epithelium (RPE), p62DNA administration slowed down development of destructive alterations of RPE cells, including loss of regular hexagonal shape, hypertrophy, and multinucleation. In neuroretina, p 62DNA prevented gliosis, retinal thinning, and significantly inhibited microglia/macrophages migration to the outer retina. Taken together, these results suggest that the p62 DNA has a strong retinoprotective effect in AMD. Dr. Alexander Shneider and Dr. Nataliya Kolosova said, "Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in industrialized countries." AMD is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. There are effective treatments of vascular complications of AMD by anti-VEGF therapeutics. Retinopathy that develops in OXYS rats even at a young age corresponds (in terms of clinical manifestations and morphological characteristics) to the dry atrophic form of AMD in humans. The Shneider/Kolosova Research Team concluded in their Aging-US Research Output, "our data suggests that a p62-encoding plasmid might be a novel preventive and/or therapeutic agent for AMD as it maintained retinal thickness and restored RPE morphology." Full Text - https://www.aging-us.com/article/101537/text Correspondence to: Alexander Shneider email: ashneider@curelab.com and Nataliya Kolosova email: kolosova@bionet.nsc.ru Keywords: p62/SQSTM1, age-related macular degeneration, inflammation, gliosis, OXYS rats, aging, retina 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

Sarcopenia is a common clinical condition that befalls the elderly—defined as a loss of skeletal muscle and muscle strength. Sarcopenic patients share clinical features with physical frailty (a subtype of the condition of frailty). Frailty is a broadly defined condition that typically encompasses multiple domains of aging, including cognitive impairment and decreased mobility and social activity. Sarcopenia and frailty are both deeply affected by aging, however, the underlying metabolic bases they stem from have remained unclear. How molecularly similar are sarcopenia and frailty? Are they spawned from the same cause? “[…] little is known about the metabolic basis of sarcopenia, either shared with or discrete from frailty.” In 2021, researchers from Kyoto University and Okinawa Institute of Science and Technology Graduate University collected blood samples from a cohort of elderly participants (from a previous study on frailty), and analyzed the samples in relation to sarcopenia. Their research paper was published as the cover of Aging (Aging-US) Volume 13, Issue 17, and entitled, “Reduced uremic metabolites are prominent feature of sarcopenia, distinct from antioxidative markers for frailty.” Full blog - https://www.impactjournals.com/journals/blog/aging/trending-with-impact-metabolomics-discerns-sarcopenia-from-frailty/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203498 DOI - https://doi.org/10.18632/aging.203498 Full text - https://www.aging-us.com/article/203498/text Correspondence to: Mitsuhiro Yanagida email: myanagid@gmail.com Keywords: sarcopenia, muscle mass, metabolomics, frailty, uremic metabolites, aging 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: Twitter - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ SoundCloud - https://soundcloud.com/aging-us​ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ 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 "The expression of C1 inhibitor (C1INH) in macrophages is upregulated by retinal pigment epithelial cells – implication in subretinal immune privilege in the aging eye" which reported that this study aimed to understand how complement expression in macrophages is regulated by retinal pigment epithelium (RPE) RPE can modulate macrophage complement expression at the retina-choroidal interface even under aging or oxidative conditions. During inflammation, they may promote the alternative pathway of complement activation through down-regulating CFH and CD59a and upregulating C3, CFB and C1INH. When BMDMs were treated with apoptotic RPE, the expression of C1qb, CFH, and CD 59a was reduced but increased in BMDM. TNF-α pre-treated RPE enhanced C1inH and CFB expression. Dr. Heping Xu from The Queen’s University Belfast as well as The Central South University said, "The neuronal retina is segregated from the systemic immune system by the blood retina barriers (BRB) and is considered as an immune privileged tissue." The immune suppressive microenvironment of the eye is critical for retinal immune privilege. Despite the lack of systemic immune surveillance, the retina is well-protected by its own innate immune defence system, including innate immune cells and the complement system. During aging, the expression of complement proteins or fragments is increased in the retina, particularly at the retina-choroid interface. Subretinal macrophages in the healthy adult eyes (6 -12 months old) often have a small soma and long- fine-dendrites (Fig. 1A), whereas the cells in the aging eye (20 – 27 months) have a large cell body that often contains pigmented debris. This suggests that they are active phagocytizing debris released by stressed RPE cells. The Xu Research Team concluded in their Aging-US Research Output, "we show that RPE cells can modulate macrophage complement expression. Under normal aging conditions, RPE cells may convert macrophages into a phenotype that can suppress complement activation with enhanced phagocytosis. This immune regulatory function of RPE cells on macrophages may be lost under inflammatory conditions. Instead, inflammatory or apoptotic RPE cells promote macrophages to produce complement components necessary for the AP activation. RPE cells together with subretinal macrophages critically control complement activation at the retina-choroid interface in the ageing eye." Full Text - https://www.aging-us.com/article/101474/text Correspondence to: Heping Xu email: heping.xu@qub.ac.uk Keywords: macrophages, retinal pigment epithelial cells, complement, aging, subretinal immune privilege 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 recently published "Alzheimer’s disease as a systems network disorder: chronic stress/dyshomeostasis, innate immunity, and genetics" which reported that ineffective results of clinical trials of over 200 anti-Alzheimer's drug candidates, with a 99.6% attrition rate, suggest that the current paradigm of Alzheimer's disease may be incomplete, necessitating exploration of alternative and complementary frameworks. Results of this analysis suggest that Alzheimer’s may not be a brain disease but a progressive system-level network disorder, which is driven by chronic network stress and dyshomeostasis. The latter can be caused by various endogenous and exogenous factors, such as chronic inflammatory conditions, infections, vascular dysfunction, head trauma, environmental toxicity, and immune disorders. Whether originating in the brain or on the periphery, chronic stress, toxicity, and inflammation are communicated to the central nervous system via humoral and neural routes, preferentially targeting high-centrality regulatory nodes and circuits of the nervous system, and eventually manifesting as a neurodegenerative CNS disease. In this report, the Aging-US authors outline an alternative perspective on AD as a systems network disorder and discuss biochemical and genetic evidence suggesting the central role of chronic tissue injury/dyshomeostasis, innate immune reactivity, and inflammation in the etiopathobiology of Alzheimer’s disease. Dr. Alexei Kurakinn and Dr. Dale E. Bredesen said, "Alzheimer’s disease has become a global epidemic, rapidly advancing in the last decade to become the 5th leading cause of death globally and the 3rd leading cause of death in high-income countries." In brief, a multimodal clinical profile of a patient is used by a human expert to generate a representative set of terms that characterize the disease configuration of the patient. The generated set serves as a query to search research literature and databases for information blocks with highest densities of query terms. Selected and rank-ordered blocks of information are analyzed by an expert to identify a parsimonious set of concepts that interconnect cliques of search terms. The identified concepts are then used as new or additional query terms in the next iteration to identify higher level connectors, until all search terms become assimilated within a parsimoniously interconnected network. Analysis of the generated disease network by a human expert allows for formulation of de novo hypotheses. Although searches are non-exhaustive and hypothesis generation is inevitably biased by idiosyncratic expertise and choices of human expert, the relative worth of a generated hypothesis is measured in terms of its practical utility by testing hypothesis’ predictions empirically and/or in silico. The implications of the proposed systemic nature of Alzheimer’s disease for treatment and prevention of cognitive decline are briefly discussed. The Kurakinn/Bredesen Research Team concluded in their Aging-US Research Paper that the promising results of an integrative, systemic, precision medicine approach to treating Alzheimer’s disease suggests that evaluating and addressing the individual organism as a whole rather than focusing exclusively on an apparently failing part may represent a promising strategy to approach other complex chronic multifactorial disorders, which warrants further exploration and development. Full Text - https://doi.org/10.18632/aging.103883 Correspondence to: Alexei Kurakin email: akurakin@mednet.ucla.edu and Dale E. Bredesen email: dbredesen@mednet.ucla.edu Keywords: Alzheimer’s disease, neurodegeneration, complex chronic disorder, network biology, systems biology

Aging-US published a Special Collection on Eye Disease which included "Loss of NAMPT in aging retinal pigment epithelium reduces NAD+ availability and promotes cellular senescence" which reported that retinal pigment epithelium performs numerous functions critical to retinal health and visual function. Here, the authors evaluated the temporal expression of key nicotinamide adenine dinucleotide -biosynthetic genes and associated levels of NAD+, a principal regulator of energy metabolism and cellular fate, in mouse RPE. They simulated in vitro the age-dependent decline in NAD+ and the related increase in RPE senescence in human and mouse primary RPE using the NAMPT inhibitor FK866 and demonstrated the positive impact of NAD+-enhancing therapies on RPE cell viability. This was confirmed in vivo in the RPE of mice injected sub-retinally with FK866 in the presence or absence of nicotinamide mononucleotide. Dr. Pamela M. Martin and Dr. Ravirajsinh N. Jadeja said, "The retinal pigment epithelium (RPE) performs numerous functions essential to normal retinal health and function." RPE serves as a physiologic barrier between the photoreceptor cells and the choroidal blood supply and in doing so, plays an essential role in protecting the retina from systemic insults by regulating immune responses and thereby limiting the entry of infectious or otherwise detrimental agents into retina. This is the premise of a number of recent studies including the present investigation in which we focused on nicotinamide adenine dinucleotide and factors governing its bioavailability in relation to the overall impact on RPE viability. NAD+, a central metabolic cofactor, plays a critical role in regulating cellular metabolism and energy homeostasis. The ratio of NAD+ to NADH regulates the activity of various enzymes essential to metabolic pathways including glycolysis, the Kreb’s cycle, and fatty acid oxidation. There is a wealth of clinical and experimental data stemming from studies of other primary diseases of aging demonstrating clearly a generalized decline in the availability of NAD+ in association with increased age and the related reduction in the activity of a number of downstream metabolic pathways that contribute to the development and progression of degenerative processes. Members of the sirtuin family, poly ADP-ribose polymerases and the efficacy of therapies capable of impacting them have been evaluated in the context of aging retina and RPE. However, little attention has been given to upstream factors that regulate NAD+ biosynthesis, particularly in RPE. Given the importance of RPE to retinal health and function, in the present investigation we focused on evaluating the impact of NAD+ and factors that regulate its availability on RPE viability both in vivo and in vitro. This finding is highly relevant to the clinical management of AMD but perhaps also broadly to the management of other degenerative retinal diseases in which RPE is prominently affected. The Martin/Jadeja Research Team concluded in their Aging-US Research Output that these present data demonstrating an age-dependent decline in NAMPT expression and in turn, NAD+ generation in RPE which ultimately promotes RPE senescence supports strongly the rationale for enhancing NAMPT expression and associated NAD+ generation therapeutically. Based upon the present experimental observations, future preclinical studies evaluating NMN or other therapies that have a direct impact on NAMPT expression and NAD+ metabolism in the context of aging and age-related retinal disease development and progression are highly warranted. Full Text - https://www.aging-us.com/article/101469/text Correspondence to: Pamela M. Martin email: pmmartin@augusta.edu and Ravirajsinh N. Jadeja email: rjadeja@augusta.edu Keywords: retinal pigment epithelium (RPE), aging, age-related macular degeneration, NAD+, NAMPT, senescence, SIRT1