Aging-US

BUFFALO, NY- October 4, 2023 – 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 18, entitled, “Biomedical generative pre-trained based transformer language model for age-related disease target discovery.” Target discovery is crucial for the development of innovative therapeutics and diagnostics. However, current approaches often face limitations in efficiency, specificity, and scalability, necessitating the exploration of novel strategies for identifying and validating disease-relevant targets. Advances in natural language processing have provided new avenues for predicting potential therapeutic targets for various diseases. In their new study, researchers Diana Zagirova, Stefan Pushkov, Geoffrey Ho Duen Leung, Bonnie Hei Man Liu, Anatoly Urban, Denis Sidorenko, Aleksandr Kalashnikov, Ekaterina Kozlova, Vladimir Naumov, Frank W. Pun, Ivan V. Ozerov, Alex Aliper, and Alex Zhavoronkov from Insilico Medicine present a novel approach for predicting therapeutic targets using a large language model (LLM). “We trained a domain-specific BioGPT model on a large corpus of biomedical literature consisting of grant text and developed a pipeline for generating target prediction.” This study demonstrates that pre-training of the LLM model with task-specific texts improves its performance. Applying the developed pipeline, the researchers retrieved prospective aging and age-related disease targets and showed that these proteins are in correspondence with the database data. Moreover, they propose CCR5 and PTH as potential novel dual-purpose anti-aging and disease targets which were not previously identified as age-related but were highly ranked in their approach. “Overall, our work highlights the high potential of transformer models in novel target prediction and provides a roadmap for future integration of AI approaches for addressing the intricate challenges presented in the biomedical field.” DOI - https://doi.org/10.18632/aging.205055 Corresponding author - Alex Zhavoronkov - alex@insilico.com Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205055 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, transformers, deep learning, therapeutic target discovery, aging biomarkers, human 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 https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ X - 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

BUFFALO, NY- October 2, 2023 – A new priority 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 18, entitled, “Gene expression signatures of human senescent corneal and conjunctival epithelial cells.” In this new study, researchers Koji Kitazawa, Akifumi Matsumoto, Kohsaku Numa, Yasufumi Tomioka, Zhixin A. Zhang, Yohei Yamashita, Chie Sotozono, Pierre-Yves Desprez, and Judith Campisi from the Buck Institute for Research on Aging, Kyoto Prefectural University of Medicine and Lawrence Berkeley National Laboratory aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells. “Here, we induced cellular senescence in human corneal and conjunctival epithelium using X-irradiation, and analyzed gene expression profiles of each cell type to determine the characteristics of senescent ocular surface cells.” The team examined cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, and expression of senescence markers (p16 and p21). RNA sequencing analysis was conducted to compare gene expression profiles between senescent and non-senescent cells. Finally, the potential involvement of senescent cells in the pathogenesis of ocular surface diseases was investigated. X-irradiated corneal and conjunctival epithelial cells exhibited typical senescence phenotypes, i.e., flattened morphologies, increased SA-β-gal activity, decreased cell proliferation, and increased expression of senescence markers, p16 and p21. RNA-seq analysis revealed substantial differences in gene expression profiles between senescent corneal (SCo) and conjunctival epithelial cells (SCj). Moreover, SCj were detected in pathological conjunctival tissues associated with limbal stem cell deficiency (LSCD) due to Stevens-Johnson syndrome or chemical burns, potentially being involved in abnormal differentiation. “This study highlights the cellular and molecular characteristics of senescent ocular surface cells, particularly in SCj that show abnormal keratin expression, and their potential roles in severe ocular surface diseases and pathology.” DOI - https://doi.org/10.18632/aging.205113 Corresponding authors - Koji Kitazawa - kkitazaw@koto.kpu-m.ac.jp, and Judith Campisi - jcampisi@buckinstitute.org Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205113 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, cornea, conjunctiva, Stevens-Johnson syndrome, limbal stem cell deficiency 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

R-loops are structures that form when the nascent RNA hybridizes with the template DNA strand, displacing the non-template strand. Nascent RNA refers to the newly synthesized RNA molecule that is produced during the process of transcription. Transcription is the first step in gene expression where the information in a DNA sequence is used to create an RNA molecule. In addition to transcription, R-loops are involved in various biological processes, such as splicing, DNA repair and chromatin remodeling. However, when R-loop homeostasis is disrupted, they can also cause transcriptional impairment, genome instability and cellular dysfunction. "R-loops have been shown and studied in a wide range of organisms and while they have important regulatory roles, persistent R-loops can be detrimental to cell function and survival, having been closely linked to both gene expression dysregulation and increased genome instability." In a new editorial paper, researcher Hana Hall from the Purdue Institute for Integrative Neuroscience at Purdue University, discusses the role of R-loops in neuronal aging and neurodegeneration. On September 13, 2023, her editorial was published in Aging’s Volume 15, Issue 17, and entitled, “R-loops in neuronal aging.” Hall summarizes her recent study and the current knowledge on how R-loop levels change during aging, how they affect gene expression and neuronal function, and how they are regulated by different factors. Full blog - https://aging-us.org/2023/09/the-role-of-r-loops-in-neuronal-aging/ Paper DOI - https://doi.org/10.18632/aging.205070 Corresponding author - Hana Hall - hallh@purdue.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205070 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, R-loops, neuron, transcription, genome instability, neurodegeneration 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/ X - 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

BUFFALO, NY- September 27, 2023 – A new editorial paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 17, entitled, “Promising trends in lung cancer care, but are we overlooking the majority?” In their new editorial, researchers Bhavina Sharma and Apar Kishor Ganti from the University of Nebraska Medical Center discuss challenges and opportunities for better lung cancer care for the elderly. Lung cancer is the third most common cancer in the United States, after female breast cancer and prostate cancer. It accounts for more cancer-related deaths in both men and women than any other types of cancer. The incidence of new lung cancer has decreased between 1999-2019, mirroring the fall in tobacco use in the past few decades. Lung cancer-related mortality has also decreased with the recent advances in screening techniques and treatment strategies. However, the incidence of lung cancer and lung cancer mortality is still disproportionately higher among older patients (65 years and older). Multiple studies have shown that older patients are more likely to be undertreated because of their chronological age, even after accounting for their comorbidities and socioeconomic status. Common reasons for this disparity are insufficient study evidence, lack of appropriate resources and support, patient factors such as socioeconomic status, as well as variations in individual physician practices and preferences. Even though the median age of lung cancer diagnosis is 71 years, and more than two-thirds of patients are older than 65 years, older patients are less likely to be enrolled in clinical trials. “Although there is now increasing effort and guidance by major cancer societies and regulatory groups to increase inclusion of older patients, better conscious collaboration between the stakeholders is necessary for effective implementation of the strategies discussed and to enhance enrollment and retention of older cancer patients.” DOI - https://doi.org/10.18632/aging.204662 Corresponding author - Apar Kishor Ganti - aganti@unmc.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204662 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, lung cancer, clinical trials 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/ X - 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

BUFFALO, NY- September 26, 2023 – 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 17, entitled, “Availability of living donor optimizes timing of liver transplant in high-risk waitlisted cirrhosis patients.” Liver transplant (LT) candidates have become older and frailer. Growing non-alcoholic steatohepatitis (NASH) and comorbid disease burden in recent years is also predisposing them for poor waitlist outcomes. In this new study, researchers Fakhar Ali Qazi Arisar, Shiyi Chen, Catherine Chen, Noorulsaba Shaikh, Ravikiran Sindhuvalada Karnam, Wei Xu, Sumeet K. Asrani, Zita Galvin, Gideon Hirschfield, Keyur Patel, Cynthia Tsien, Nazia Selzner, Mark Cattral, Leslie Lilly, and Mamatha Bhat from the University Health Network, University of Toronto, Baylor University Medical Center, and Dow University of Health Sciences aimed to evaluate the impact of access to living donor liver transplantation (LDLT) in waitlisted patients at highest risk of dropout. “We reviewed all adult patients with decompensated cirrhosis listed for LT from November 2012 to December 2018.” Patients with a potential living donor (pLD) available were identified. Survival analyses with Cox Proportional Hazards models and time to LT with Competing risk models were performed followed by prediction model development. Out of 860 patients who met inclusion criteria, 360 (41.8%) had a pLD identified and 496 (57.6%) underwent LT, out of which 170 (34.2%) were LDLT. The benefit of pLD was evident for all, but patients with moderate to severe frailty at listing (interaction p = 0.03), height <160 cm (interaction p = 0.03), and Model for end-stage liver disease (MELD)-Na score <20 (interaction p < 0.0001) especially benefited. “Our study identifies that certain patient subgroups (short stature, MELD <20, and moderate to severe frailty) are at the highest risk for waitlist mortality with prolonged waiting time for a deceased donor organ offer. These patient subgroups, which represent a growing share of the waitlist population in recent years, would be especially protected against death or delisting if they had access to living donation at the time of listing. Certainly, LDLT is beneficial to all, with improved waitlist mortality and post-transplant outcomes.” DOI - https://doi.org/10.18632/aging.204982 Corresponding author - Mamatha Bhat - mamatha.bhat@uhn.ca Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204982 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, living donor liver transplant, frailty, old age, short-statured, MELD score, prediction model 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

BUFFALO, NY- September 20, 2023 – 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 17, entitled, “Development of a DNA damage-induced senescence model in osteoarthritic chondrocytes.” Senescent cells (SnCs) have been described to accumulate in osteoarthritis (OA) joint tissues in response to injury, thereby participating in OA development and progression. However, clinical therapeutic approaches targeting SnCs using senolysis, although promising in preclinical OA models, have not yet proven their efficacy in patients with knee OA. This pitfall may be due to the lack of understanding of the mechanisms underlying chondrocyte senescence. In their new study, researchers Mélina Georget, Anaïs Defois, Romain Guiho, Nina Bon, Sophie Allain, Cécile Boyer, Boris Halgand, Denis Waast, Gaël Grimandi, Alban Fouasson-Chailloux, Jérôme Guicheux, and Claire Vinatier from Nantes Université aimed to generate models of chondrocyte senescence. “In this context, our study aims to develop in vitro models of chondrocyte senescence by investigating the ability of etoposide and IL-1β treatments to produce a reliable chondrocyte senescent model.” This study used etoposide, to induce DNA damage-related senescence or chronic exposure to IL-1β to entail inflammation-related senescence in human OA chondrocytes. Several hallmarks of cellular senescence, such as cell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associated secretory profile were evaluated. Chronic exposure to IL-1β induces only partial expression of senescence markers and does not allow us to conclude on its ability to induce senescence in chondrocytes. On the other hand, etoposide treatment reliably induces DNA damage-related senescence in human articular chondrocytes evidenced by loss of proliferative capacity, DNA damage accumulation, and expression of some SASP components. “Etoposide-induced senescence model may help investigate the initiation of cellular senescence in chondrocytes, and provide a useful model to develop therapeutic approaches to target senescence in OA.” DOI - https://doi.org/10.18632/aging.204881 Corresponding author - Claire Vinatier - claire.vinatier@univ-nantes.fr Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204881 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, osteoarthritis, etoposide, chondrocytes 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/ X - 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 priority 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 17, entitled, “Fail-tests of DNA methylation clocks, and development of a noise barometer for measuring epigenetic pressure of aging and disease.” In this new study, researchers Xiaoyue Mei, Joshua Blanchard, Connor Luellen, Michael J. Conboy, and Irina M. Conboy from the University of California, Berkeley, show that Elastic Net (EN) DNA methylation (DNAme) clocks have low accuracy of predictions for individuals of the same age and a low resolution between healthy and disease cohorts; caveats inherent in applying linear model to non-linear processes. “We found that change in methylation of cytosines with age is, interestingly, not the determinant for their selection into the clocks.” Moreover, an EN clock’s selected cytosines change when non-clock cytosines are removed from the training data; as expected from optimization in a machine learning (ML) context, but inconsistently with the identification of health markers in a biological context. To address these limitations, the researchers moved from predictions to measurement of biological age, focusing on the cytosines that on average remain invariable in their methylation through lifespan, postulated to be homeostatically vital. They established that dysregulation of such cytosines, measured as the sums of standard deviations of their methylation values, quantifies biological noise, which in their hypothesis is a biomarker of aging and disease. “We term this approach a ‘noise barometer’ - the pressure of aging and disease on an organism.” These noise-detecting cytosines are particularly important as sums of SD on the entire 450K DNAme array data yield a random pattern through chronology. Testing how many cytosines of the 450K arrays become noisier with age, the team found that the paradigm of DNAme noise as a biomarker of aging and disease remarkably manifests in ~1/4 of the total. In that large set even the cytosines that have on average constant methylation through age show increased SDs and can be used as noise detectors of the barometer. DOI - https://doi.org/10.18632/aging.205046 Corresponding author - Irina M. Conboy - iconboy@berkeley.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205046 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, DNA methylation, epigenetics, clocks’ fail-test, biological noise 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

In the realm of cancer research, one persistent trend has emerged — the incidence of invasive melanoma rises steadily with advancing age. While this insidious disease remains rare in children and adolescents, it progressively asserts its presence as individuals grow older. The connection between age and melanoma incidence persists around the world, albeit with varying rates in different countries. Australia has the highest melanoma rates in the world. According to the Melanoma Institute Australia, every 30 minutes an Australian is diagnosed with melanoma and every 6 hours an Australian dies from it. Thankfully, research is making a difference. In the last decade, the 5-year overall survival rate for advanced melanoma has increased from less than 10% to more than 50%. In 2011, melanoma was Australia’s 7th most deadly cancer. In 2021, melanoma was Australia’s 11th most deadly cancer. In a new editorial paper, researchers John F. Thompson and Gabrielle J. Williams from the Melanoma Institute Australia at The University of Sydney discuss the intricacies of how age influences different varieties of melanoma incidence, prognosis and treatment. On August 17, 2023, their editorial was published in Aging’s Volume 15, Issue 16, entitled, “The effect of age on melanoma incidence and prognosis.” Full blog - https://aging-us.org/2023/09/the-impact-of-age-on-melanoma-insights-from-recent-research/ Paper DOI - https://doi.org/10.18632/aging.204653 Corresponding author - John F. Thompson - john.thompson@melanoma.org.au Video short - https://www.youtube.com/watch?v=V0wwfLEJGW0 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204653 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, melanoma, incidence, age, prognosis 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/ X - 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 editorial paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 16, entitled, “Microvascular contributions to white matter injury in Alzheimer’s disease.” In their new editorial, researchers Zsolt Bagi, Larry S. Sherman and Stephen A. Back from Augusta University discuss mechanisms of cognitive impairment and dementia. Impairments in cognitive and executive function of presumed cerebral microvascular origin are important and recently recognized neuropathological manifestations of vascular contributions to cognitive impairment and dementia (VCID). It has been long known that hypertensive cerebrovascular disease also involves a spectrum of subcortical small vessel diseases, such as arteriolosclerosis and lipohyalinosis of small penetrating arterioles, which contribute to progressive injury of periventricular, frontal and parietal white matter (WM). “However, until recently, recognition of the role of WM injury during aging and the progression of Alzheimer disease and related dementias (AD/ADRD) was very limited.” Despite growing interest in VCID and AD/ADRD, there have been few studies of mechanistic links between subcortical small vessel disease, WM injury and cognitive decline. Even though WM constitutes >80% of the human cerebral hemispheres, a PubMed search of AD and WM injury yielded only 381 articles (including reviews) vs. 193,303 articles for AD alone. Notably, 50% of diagnosed AD patients have mixed vascular and AD pathology. Hence, there is a critical need to explore connections between AD, WM injury and cerebral small vessel disease to define mechanisms and diagnostic features of mixed vascular and AD neuropathological change (ADNC). “To provide rigorous access to human WM lesions, we recently developed a unique rapid autopsy brain procurement protocol using specimens donated by participants in the Adult Changes in Thought (ACT) study, a prospective, population-based study of aging and incident dementia among men and women in Seattle, Washington [5].” DOI - https://doi.org/10.18632/aging.204997 Corresponding author - Zsolt Bagi - zbagi@augusta.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204997 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cerebrovascular, neuropathology, vasodilation, parenchymal, arteriole 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 16, entitled, “Copy number variation as a tool for implementing pregnancy as an aging model.” Copy number variations (CNV) are a major contributor to genome variability. CNVs have been linked to aging and other degradable phenotypes such as pregnancy physiology. In this new study, researchers Mariana Andrawus, Lital Sharvit, Noga Touitou, Batia Lerrer, Haim Y. Cohen, and Gil Atzmon from University of Haifa and Bar-Ilan University used CNVs from pregnant mice to demonstrate how pregnancy can be used as a model of aging. “We hypothesize that pregnancy can serve as a model for aging by demonstrating similar biomarkers, pathologies, and genetic and epigenetic effects [3]. To test this hypothesis, we designed a study that assesses CNVs associated with human longevity (unpublished results) in pregnancy.” Candidate CNVs were selected by applying case-control analysis in human centenarians compared with control groups. These CNVs were aligned with the mouse genome and their copy variation was assessed using qRT-PCR in liver and blood tissue samples from pregnant mice throughout pregnancy (baseline; first, second, and third trimester; post-partum). Eight of the ten selected CNVs demonstrated a significant decline/increase trend throughout the pregnancy followed by opposite direction soon after delivery in the liver and blood of the mouse tissues. Furthermore, significant differential expression was detected among the candidate CNVs’ close vicinity genes (APA2A, LSS, RBDHF1, PLAAT1, and SCL17A2), but not in the WSCD2 gene. Establishing a genetic link between longevity and pregnancy is a significant step toward implementing the pregnancy process as a model for aging. These results in pregnant mice highlight the mechanism and similarities between pregnancy and aging. “Investigating the mechanisms that cause such rejuvenation after labor could change our aging treatment paradigm.” DOI - https://doi.org/10.18632/aging.204936 Corresponding author - Gil Atzmon - gatzmon@univ.haifa.ac.il Video short - https://www.youtube.com/watch?v=82466m-S-tU Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204936 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, pregnancy, copy number variation, gene expression 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