Aging-US

Blog summary of a research paper published by Aging (Aging-US) in Volume 15, Issue 8: "Identification of dual-purpose therapeutic targets implicated in aging and glioblastoma multiforme using PandaOmics – an AI-enabled biological target discovery platform.” _____________________________________________________ Glioblastoma multiforme (GBM) is one of the most aggressive and fatal malignant brain tumors. With a median survival time of 15 months, only about 25% of patients survive for one year and less than 5% survive for five years. As people get older, the risk of developing GBM increases. The discovery of new drug targets for GBM is of paramount importance. The good news here is that high school students, Zachary Harpaz, Andrea Olsen and Christopher Ren, and researchers Anastasia Shneyderman, Alexander Veviorskiy, Maria Dralkina, Simon Konnov, Olga Shcheglova, Frank W. Pun, Geoffrey Ho Duen Leung, Hoi Wing Leung, Ivan V. Ozerov, Alex Aliper, Mikhail Korzinkin, and Alex Zhavoronkov have recently made remarkable strides in the joint field of aging and glioblastoma research. The team used a generative artificial intelligence (AI) engine from Insilico Medicine (founded by Dr. Alex Zhavoronkov) called PandaOmics, to identify new therapeutic targets for both GBM and aging. On April 26, 2023, their research paper was published in Aging’s Volume 15, Issue 8, entitled, “Identification of dual-purpose therapeutic targets implicated in aging and glioblastoma multiforme using PandaOmics – an AI-enabled biological target discovery platform.” Full blog - https://aging-us.org/2023/05/high-school-students-use-ai-to-make-aging-and-glioblastoma-discoveries/ Research paper DOI - https://doi.org/10.18632/aging.204678 Corresponding author - Mikhail Korzinkin - mike@insilicomedicine.com Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204678 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, target discovery, GBM, glioblastoma, PandaOmics 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 https://www.Aging-US.com​​ and connect with us: 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/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (Aging-US) Volume 15, Issue 8, entitled, “Identification of dual-purpose therapeutic targets implicated in aging and glioblastoma multiforme using PandaOmics - an AI-enabled biological target discovery platform.” Glioblastoma Multiforme (GBM) is the most aggressive and most common primary malignant brain tumor. The age of GBM patients is considered as one of the disease's negative prognostic factors and the mean age of diagnosis is 62 years. A promising approach to preventing both GBM and aging is to identify new potential therapeutic targets that are associated with both conditions as concurrent drivers. In this new study, researchers Anastasia Shneyderman, Alexander Veviorskiy, Maria Dralkina, Simon Konnov, Olga Shcheglova, Frank W. Pun, Geoffrey Ho Duen Leung, Hoi Wing Leung, Ivan V. Ozerov, Alex Aliper, Mikhail Korzinkin, and Alex Zhavoronkov from The Youth Longevity Association, Pine Crest School Science Research Department, Shanghai High School International Division, and Insilico Medicine present a multi-angled approach of identifying targets, which takes into account not only the disease-related genes but also the ones important in aging. “For this purpose, we developed three strategies of target identification using the results of correlation analysis augmented with survival data, differences in expression levels and previously published information of aging-related genes.” Several studies have recently validated the robustness and applicability of AI-driven computational methods for target identification in both cancer and aging-related diseases. Therefore, the researchers leveraged the AI predictive power of the PandaOmics TargetID engine in order to rank the resulting target hypotheses and prioritize the most promising therapeutic gene targets. They propose three potentially novel dual-purpose therapeutic targets to treat aging and GBM: cyclic nucleotide gated channel subunit alpha 3 (CNGA3), glutamate dehydrogenase 1 (GLUD1) and sirtuin 1 (SIRT1). “The next steps towards implementation of the identified therapeutic targets into the clinic would involve a generation of small molecules and their optimisation with further validation and preclinical testing to determine their safety, efficacy, and potential side effects.” DOI: https://doi.org/10.18632/aging.204678 Corresponding author - Mikhail Korzinkin - mike@insilicomedicine.com Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204678 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, target discovery, GBM, glioblastoma, PandaOmics 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 https://www.Aging-US.com​​ and connect with us: 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/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 8, entitled, “A chronic wound model to investigate skin cellular senescence.” Wound healing is an essential physiological process for restoring normal skin structure and function post-injury. The role of cellular senescence, an essentially irreversible cell cycle state in response to damaging stimuli, has emerged as a critical mechanism in wound remodeling. Transiently-induced senescence during tissue remodeling has been shown to be beneficial in the acute wound healing phase. In contrast, persistent senescence, as observed in chronic wounds, contributes to delayed closure. In this new study, researchers Saranya P. Wyles, Parisa Dashti, Tamar Pirtskhalava, Burak Tekin, Christina Inman, Lilian Sales Gomez, Anthony B. Lagnado, Larissa Prata, Diana Jurk, João F. Passos, Tamar Tchkonia, and James L. Kirkland from the Mayo Clinic in Rochester, Minnesota, describe a chronic wound murine model and its cellular senescence profile, including the senescence-associated secretory phenotype. “Herein we hypothesize that persistent senescent cell accumulation contributes to delayed healing in chronic wounds.” This study presents a novel oxidative stress-induced chronic murine wound mouse model in which there is capacity to target aberrant senescent cell expression. Pharmacological manipulation of oxidative stress can influence wound healing and result in delayed wound closure, which offers the opportunity to characterize cellular senescence in late stages of wound healing. The molecular and histological profiles of senescent cells in the epidermis and dermis demonstrate the adverse influence of SASP factors in the chronic wound bed, a new avenue for root-cause, targeted therapeutic interventions. “To our knowledge, this study is the first chronic wound murine model to profile the effects of the chronic cellular senescence that is linked to delayed wound healing. This may have implications for developing interventions that target cellular senescence for chronic or stalled wounds as a root cause-driven therapeutic strategy.” DOI: https://doi.org/10.18632/aging.204667 Corresponding Authors: James L. Kirkland - kirkland.james@mayo.edu, and Tamar Tchkonia - tchkonia.tamar@mayo.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204667 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, wound healing, cellular senescence, chronic wound, re-epithelization, skin 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 https://www.Aging-US.com​​ and connect with us: 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/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (Aging-US) Volume 15, Issue 7, entitled, “Effect of deferoxamine and ferrostatin-1 on salivary gland dysfunction in ovariectomized rats.” Xerostomia can be defined as a subjective sensation associated with reduction of lubrication and dehydration of the oral mucosa. Xerostomia is known to be common in elderly people, especially women, and its prevalence is thought to range from 5.5% to 46%. The mechanism underlying xerostomia after menopause has not yet been fully elucidated. In this new study, researchers Yong-Il Cheon, Ji Min Kim, Sung-Chan Shin, Hyung-Sik Kim, Jin-Choon Lee, Gi Cheol Park, Eui-Suk Sung, Minhyung Lee, and Byung-Joo Lee from Pusan National University and Sungkyunkwan University School of Medicine aimed to investigate the mechanism of xerostomia and the effect of the ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (FER) on salivary gland dysfunction in a postmenopausal animal model. “Recently, it was reported that ferroptosis in the salivary gland may be related to the xerostomia that occurs after menopause [30]. However, no studies to date have used anti-ferroptosis drugs to investigate the mechanisms underlying postmenopausal salivary gland dysfunction.” Twenty-four female Sprague–Dawley rats were randomly divided into four groups: a SHAM group (n = 6, sham-operated rats), an OVX group (n = 6, ovariectomized rats), an FER group (n = 6, ovariectomized rats injected intraperitoneally with FER), and a DFO group (n = 6, ovariectomized rats injected intraperitoneally with DFO). GPX4 activity, iron accumulation, lipid peroxidation, inflammation, fibrosis, and salivary gland function were analyzed. Recovery of GPX4 activity and a decrease in iron accumulation and cytosolic MDA + HAE were observed in the DFO group. In addition, collagen I, collagen III, TGF-β, IL-6, TNF-α, and TGF-β levels were decreased in the DFO group compared to the OVX group. Recovery of GPX4 activity and the morphology of mitochondria, and reduction of cytosolic MDA + HAE were also observed in the FER group. In addition, decreased expression of inflammatory cytokines and fibrosis markers and increased expression of AQP5 were observed in both the DFO and FER groups. Postmenopausal salivary gland dysfunction is associated with ferroptosis. This is the first study to investigate the effect of ferroptosis inhibitors (DFO and FER) on the salivary glands of ovariectomized rats. DFO and FER are considered promising treatments for postmenopausal xerostomia. “In the absence of a standard treatment for postmenopausal dry mouth, this study is expected to be helpful in understanding the mechanism of postmenopausal salivary gland dysfunction and developing a treatment for postmenopausal dry mouth.” DOI: https://doi.org/10.18632/aging.204641 Corresponding author - Byung-Joo Lee - voicelee@pusan.ac.kr Keywords - aging, menopause, ferroptosis, xerostomia, deferoxamine, ferrostatin-1 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. Visit our website at https://www.Aging-US.com​​ and connect with us: 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/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (Aging-US) Volume 15, Issue 7, entitled, “Characterization of the HDAC/PI3K inhibitor CUDC-907 as a novel senolytic.” The accumulation of senescent cells has an important role in the phenotypical changes observed in aging and in many age-related pathologies. Thus, the strategies designed to prevent these effects, collectively known as senotherapies, have a strong clinical potential. Senolytics are a type of senotherapy aimed at specifically eliminating senescent cells from tissues. Several small molecule compounds with senolytic properties have already been identified, but their specificity and range of action are variable. Because of this, potential novel senolytics are being actively investigated. Given the involvement of HDACs and the PI3K pathway in senescence, researchers Fares Al-Mansour, Abdullah Alraddadi, Buwei He, Anes Saleh, Marta Poblocka, Wael Alzahrani, Shaun Cowley, and Salvador Macip from the University of Leicester, Najran University and Universitat Oberta de Catalunya hypothesized that the dual inhibitor CUDC-907, a drug already in clinical trials for its antineoplastic effects, could have senolytic effects. “Here, we show that CUDC-907 was indeed able to selectively induce apoptosis in cells driven to senesce by p53 expression, but not when senescence happened in the absence of p53.” Consistent with this, CUDC-907 showed senolytic properties in different models of stress-induced senescence. Their results also indicate that the senolytic functions of CUDC-907 depend on the inhibitory effects of both HDACs and PI3K, which leads to an increase in p53 and a reduction in BH3 pro-survival proteins. Taken together, their results show that CUDC-907 has the potential to be a clinically relevant senolytic in pathological conditions in which stress-induced senescence is involved. “According to our results, CUDC-907 could be an interesting drug to be used as a senolytic, alone or as part of a targeted approach.” DOI: https://doi.org/10.18632/aging.204616 Corresponding author - Salvador Macip - sm460@le.ac.uk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204616 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, senolytics, HDAC, PI3K, CUDC-907 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 https://www.Aging-US.com​​ and connect with us: 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/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (Aging-US) Volume 15, Issue 7, entitled, “Viral vector-mediated upregulation of serine racemase expression in medial prefrontal cortex improves learning and synaptic function in middle age rats.” An age-associated decrease in N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic function contributes to impaired synaptic plasticity and is associated with cognitive impairments. Levels of serine racemase (SR), an enzyme that synthesizes D-serine, an NMDAR co-agonist, decline with age. In this new study, researchers Brittney Yegla, Asha Rani and Ashok Kumar from the University of Florida’s McKnight Brain Institute predicted that enhancing NMDAR function via increased SR expression in middle age (when subtle declines in cognition emerge) may enhance performance on a prefrontal cortex-mediated task sensitive to aging. “We hypothesized that augmenting SR expression within mPFC glutamatergic neurons would improve attention and cognitive flexibility in middle-aged rats and facilitate synaptic responses in the mPFC. Thus, for this study, SR expression was upregulated in pyramidal neurons of the mPFC through lenti-viral technology to enhance NMDAR function and evaluate its impact on cognitive flexibility and NMDAR-mediated synaptic transmission in middle-age rats.” Middle-aged (~12 mo) male Fischer-344 rats were injected bilaterally in the medial prefrontal cortex (mPFC) with viral vector (LV), SR (LV-SR) or control (LV-GFP). Rats were trained on the operant attentional set-shift task (AST) to examine cognitive flexibility and attentional function. LV-SR rats exhibited a faster rate of learning compared to controls during visual discrimination of the AST. Extradimensional set shifting and reversal were not impacted. Immunohistochemical analyses demonstrated that LV-SR significantly increased SR expression in the mPFC. Electrophysiological characterization of synaptic transmission in the mPFC slices obtained from LV-GFP and LV-SR animals indicated a significant increase in isolated NMDAR-mediated synaptic responses in LV-SR slices. Thus, results of the current study demonstrated that prefrontal SR upregulation in middle age rats can improve learning of task contingencies for visual discrimination and increase glutamatergic synaptic transmission, including NMDAR activity. “The results from this study support the beneficial effects of the D-serine pathway involvement in NMDAR-mediated transmission and cognitive function, expanding the literature to emphasize its role in not only the hippocampus but also the PFC. Thus, targeting this pathway could pose a potential route in reversing age-related cognitive decline and should be considered for future research.” DOI: https://doi.org/10.18632/aging.204652 Corresponding Author: Ashok Kumar - kash@ufl.edu Keywords - aging, medial prefrontal cortex, serine racemase, D-serine, NMDA receptor, cognitive flexibility 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 https://www.Aging-US.com​​ and connect with us: 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/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ MEDIA@IMPACTJOURNALS.COM

A new research paper was published on the cover of Aging (Aging-US) Volume 15, Issue 7, entitled, “p21 facilitates chronic lung inflammation via epithelial and endothelial cells.” Cellular senescence is a stable state of cell cycle arrest that regulates tissue integrity and protects the organism from tumorigenesis. However, the accumulation of senescent cells during aging contributes to age-related pathologies. One such pathology is chronic lung inflammation. p21 (CDKN1A) regulates cellular senescence via inhibition of cyclin-dependent kinases (CDKs). However, its role in chronic lung inflammation and functional impact on chronic lung disease, where senescent cells accumulate, is less understood. In this new study, researchers Naama Levi, Nurit Papismadov, Julia Majewska, Lior Roitman, Noa Wigoda, Raya Eilam, Michael Tsoory, Ron Rotkopf, Yossi Ovadya, Hagay Akiva, Ofer Regev, and Valery Krizhanovsky from the Weizmann Institute of Science aimed to elucidate the role of p21 in chronic lung inflammation. “[...] we subjected p21 knockout (p21-/-) mice to repetitive inhalations of lipopolysaccharide (LPS), an exposure that leads to chronic bronchitis and accumulation of senescent cells.” The researchers utilized a lipopolysaccharide (LPS) inhalation-induced chronic bronchitis procedure to study the effects of repetitive LPS exposure on p21 knockout (p21-/-) mice. Furthermore, the team aimed to examine the specific contribution of the epithelial, endothelial and immune compartments to chronic bronchitis pathology. They found that p21 knockout led to a reduced presence of senescent cells, alleviated the pathological manifestations of chronic lung inflammation, and improved the fitness of the mice. The expression profiling of the lung cells revealed that resident epithelial and endothelial cells, but not immune cells, play a significant role in mediating the p21-dependent inflammatory response following chronic LPS exposure. “Therefore, we suggest that p21-dependent elimination of senescent cells may limit the damage induced by the pro-inflammatory presence of senescent cells, but also promote tissue regeneration. Therefore, inhibition of p21 represents a promising strategy for limiting age-related inflammatory disorders in general and obstructive lung diseases in particular.” DOI: https://doi.org/10.18632/aging.204622 Corresponding Author: Valery Krizhanovsky - valery.krizhanovsky@weizmann.ac.il Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204622 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, chronic lung inflammation, p21 (CDKN1A) 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 https://www.Aging-US.com​​ and connect with us: 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/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 6, entitled, “Selenium as a predictor of metabolic syndrome in middle age women.” Metabolic syndrome (MetS) is a widespread clinical entity that has become almost a global epidemic. Selenium plays an important role in metabolic homeostasis. It has been suggested that it may also affect the expression and activity of PPAR-γ—an important mediator in energy balance and cell differentiation. In this new study, researchers Daria Schneider-Matyka, Anna Maria Cybulska, Małgorzata Szkup, Bogumiła Pilarczyk, Mariusz Panczyk, Agnieszka Tomza-Marciniak, and Elżbieta Grochans from Pomeranian Medical University in Szczecin, West Pomeranian University of Technology and Medical University of Warsaw aimed to analyze the relationships between these variables in the context of the health of women, for whom the risk of MetS increases with age. “The aim of this study was to search for a relationship between selenium concentrations and MetS, and to assess the impact of PPAR-γ on the incidence of MetS with regard to the moderating role of selenium.” The study involved 390 women in middle age. The stages of study: a survey-based part; anthropometric measurements; analysis of biological material (blood) in terms of glycemia, triglyceride, HDL, and selenium levels, as well as genetic analysis of the PPAR-γ polymorphisms. The researchers found that selenium may moderate the effect of the G allele of the PPAR-γ gene on the occurrence of elevated waist circumference (OR=1.030, 95%CI 1.005-1.057, p=0.020); and the effect of the C (OR=1.077, 95%CI 1.009-1.149, p=0.026) and the G alleles (OR=1.052, 95%CI 1.025-1.080, p<0.000) on the odds of elevated blood pressure. Women in whom HDL levels were not significantly reduced, had higher selenium levels (p=0.007). This study lead the team to 4 distinct conclusions: 1-The effect of selenium on MetS and its components has not been demonstrated. 2-The effect of individual alleles of the PPAR-γ gene on MetS and its components was not demonstrated. 3-The concentration of selenium may affect waist circumference in carriers of the G allele, and arterial hypertension in carriers of the C and G alleles by affecting the expression of PPAR-γ. 4-Higher selenium concentrations increased the odds of higher HDL levels in the group of subjects meeting the MetS criteria. “Recently, optimizing selenium intake in the population to prevent diseases associated with selenium deficiency or excess has been an important issue in modern health care worldwide. Our study suggests the influence of selenium levels on some components of MetS, such as waist circumference, blood pressure and HDL concentration. Thus, serum selenium concentration could be considered as one of the factors affecting some components of MetS.” DOI: https://doi.org/10.18632/aging.204590 Corresponding Author: Daria Schneider-Matyka - daria.schneider-matyka@pum.edu.pl Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204590 Keywords - aging, selenium, metabolic syndrome, middle aged women 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. Visit https://www.Aging-US.com​​ for more about Aging (Aging-US). MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 6, entitled, “Knockout of AMD-associated gene POLDIP2 reduces mitochondrial superoxide in human retinal pigment epithelial cells.” Genetic and epidemiologic studies have significantly advanced our understanding of the genetic factors contributing to age-related macular degeneration (AMD). In particular, recent expression quantitative trait loci (eQTL) studies have highlighted POLDIP2 as a significant gene that confers risk of developing AMD. However, the role of POLDIP2 in retinal cells such as retinal pigment epithelium (RPE) and how it contributes to AMD pathology are unknown. In this new study, researchers Tu Nguyen, Daniel Urrutia-Cabrera, Luozixian Wang, Jarmon G. Lees, Jiang-Hui Wang, Sandy S.C. Hung, Alex W. Hewitt, Thomas L. Edwards, Sam McLenachan, Fred K. Chen, Shiang Y. Lim, Chi D. Luu, Robyn Guymer, and Raymond C.B. Wong from Royal Victorian Eye and Ear Hospital, University of Melbourne, St Vincent’s Institute of Medical Research, University of Tasmania, and The University of Western Australia report the generation of a stable human RPE cell line ARPE-19 with POLDIP2 knockout using CRISPR/Cas, providing an in vitro model to investigate the functions of POLDIP2. “We conducted functional studies on the POLDIP2 knockout cell line and showed that it retained normal levels of cell proliferation, cell viability, phagocytosis and autophagy. Also, we performed RNA sequencing to profile the transcriptome of POLDIP2 knockout cells.” Their results highlighted significant changes in genes involved in immune response, complement activation, oxidative damage and vascular development. They showed that loss of POLDIP2 caused a reduction in mitochondrial superoxide levels, which is consistent with the upregulation of the mitochondrial superoxide dismutase SOD2. In conclusion, this study demonstrates a novel link between POLDIP2 and SOD2 in ARPE-19, which supports a potential role of POLDIP2 in regulating oxidative stress in AMD pathology. “In summary, we have generated a POLDIP2 knockout ARPE-19 cell line using CRISPR/Cas9 and studied the biological functions of POLDIP2. To our knowledge, this is the first functional study of POLDIP2 in retinal cells to understand its potential role in AMD.” DOI: https://doi.org/10.18632/aging.204522 Corresponding Author: Raymond C.B. Wong - wongcb@unimelb.edu.au Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204522 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, age-related macular degeneration, retina, CRISPR/Cas, mitochondria superoxide, POLDIP2 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 https://www.Aging-US.com​​ and connect with us: 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/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Blog summary of a research paper published by Aging (Aging-US) in Volume 15, Issue 6: “RNA virus-mediated changes in organismal oxygen consumption rate in young and old Drosophila melanogaster males.” _________________________________________ RNA viruses are responsible for approximately 70% of emerging infectious diseases in humans, according to a 2020 report by the National Academy of Medicine. Examples of RNA viruses include: influenza, hepatitis C, HIV, measles, zika, ebola, poliovirus, rhinovirus, rabies, and SARS-CoV-2—the virus responsible for the COVID-19 pandemic. After infection with an RNA virus, significant changes can take place in the host’s metabolism. While it is clear that disease tolerance declines as humans age, it is not yet clear how aging affects virus-induced changes in metabolism. “Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood.” In a new study, researchers Eli Hagedorn, Dean Bunnell, Beate Henschel, Daniel L. Smith Jr., Stephanie Dickinson, Andrew W. Brown, Maria De Luca, Ashley N. Turner, and Stanislava Chtarbanova from the University of Alabama, Indiana University, University of Arkansas for Medical Sciences, Arkansas Children’s Research Institute, and Jacksonville State University examined how an RNA virus can affect the respiration rate in male fruit flies (Drosophila melanogaster), both young and old. On March 22, 2023, their research paper was published in Aging’s Volume 15, Issue 6, entitled, “RNA virus-mediated changes in organismal oxygen consumption rate in young and old Drosophila melanogaster males.” Full blog - https://aging-us.org/2023/04/rna-virus-fruit-fly-model-first-study-to-measure-single-fly-respiration/ DOI - https://doi.org/10.18632/aging.204593 Corresponding author - Stanislava Chtarbanova - schtarbanova@ua.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204593 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Drosophila melanogaster, virus infection, single-fly respirometry, metabolism 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 https://www.Aging-US.com​​ and connect with us: 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/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM