Aging-US

In a new editorial, researchers discuss the impact of frailty on clinical decision-making in managing patients with atrial fibrillation and the prescription of oral anticoagulants. __ Atrial fibrillation (AF) is a type of heart arrhythmia that occurs when the ​​heart's electrical signals become irregular. This condition can increase the risk of stroke and heart failure, and becomes more common in older adults. Frailty is another condition that coincides with aging. Frailty encompasses an accumulation of deficits and can be defined as decreased physical function and resilience. For a significant proportion of the elderly population, both of these conditions coexist. This convergence can lead to additional health issues and further complicate the clinical landscape for aging individuals.  “The impact of frailty on outcomes has not been previously well characterized in populations with AF.” Studies on frailty and its overall impact on patients with AF are needed. In a new editorial paper, researchers Stephanie L. Harrison, Søren P. Johnsen and Gregory Y.H. Lip from Liverpool John Moores University and Liverpool Heart and Chest Hospital discuss some of the existing studies assessing frailty and AF in terms of patient outcomes and clinical decision-making. The researchers also discuss recommendations for clinical management of AF and frailty patients and include suggestions for future studies. On July 19, 2023, their editorial was published in Aging’s Volume 15, Issue 14, entitled, “The impact of frailty on the management of atrial fibrillation.” Full blog - https://aging-us.org/2023/08/navigating-the-frailty-factor-in-atrial-fibrillation-management/ Paper DOI - https://doi.org/10.18632/aging.204918 Corresponding author - Gregory Y.H. Lip - gregory.lip@liverpool.ac.uk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204918 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, frailty, atrial fibrillation, multimorbidity and polypharmacy, ABC pathway 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 (Aging-US) Volume 15, Issue 14, entitled, “Human senescent fibroblasts trigger progressive lung fibrosis in mice.” Cell senescence has recently emerged as a potentially relevant pathogenic mechanism in fibrosing interstitial lung diseases (f-ILDs), particularly in idiopathic pulmonary fibrosis. In a new study, researchers Fernanda Hernandez-Gonzalez, Neus Prats, Valentina Ramponi, José Alberto López-Domínguez, Kathleen Meyer, Mònica Aguilera, María Isabel Muñoz Martín, Daniel Martínez, Alvar Agusti, Rosa Faner, Jacobo Sellarés, Federico Pietrocola, and Manuel Serrano from Hospital Clinic Barcelona, The Barcelona Institute of Science and Technology (BIST), Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Barcelona, Karolinska Institute, Catalan Institution for Research and Advanced Studies (ICREA), and Altos Labs hypothesized that senescent human fibroblasts may suffice to trigger a progressive fibrogenic reaction in the lung. “Here we: (1) explored this hypothesis in vivo; (2) investigated the potential underlying biological mechanisms in vitro; and (3) studied the effects of one experimental senolytic compound (navitoclax) and two anti-fibrotic drugs currently used in the treatment of IPF in humans (nintedanib and pirfenidone), both in vivo and in vitro.” To address this, senescent human lung fibroblasts, or their secretome (SASP), were instilled into the lungs of immunodeficient mice. The researchers found that human senescent fibroblasts engraft in the lungs of immunodeficient mice and trigger progressive lung fibrosis associated to increasing levels of mouse senescent cells, whereas non-senescent fibroblasts do not trigger fibrosis. They also found that the SASP of human senescent fibroblasts is pro-senescence and pro-fibrotic both in vitro when added to mouse recipient cells and in vivo when delivered into the lungs of mice, whereas the conditioned medium (CM) from non-senescent fibroblasts lacks these activities. Finally, navitoclax, nintedanib and pirfenidone were found to ameliorate lung fibrosis induced by senescent human fibroblasts in mice, while only navitoclax displayed senolytic activity. “We conclude that human senescent fibroblasts, through their bioactive secretome, trigger a progressive fibrogenic reaction in the lungs of immunodeficient mice that includes the induction of paracrine senescence in the cells of the host, supporting the concept that senescent cells actively contribute to disease progression in patients with f-ILDs.” DOI - https://doi.org/10.18632/aging.204825 Corresponding authors - Manuel Serrano - mserrano@altoslabs.com, and Federico Pietrocola - federico.pietrocola@ki.se Keywords - aging, mouse model, cellular senescence, pulmonary fibrosis, antifibrotics, senolytic 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/ For media inquiries, please contact 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 13, entitled, “Predicting lifespan-extending chemical compounds for C. elegans with machine learning and biologically interpretable features.” Recently, there has been a growing interest in the development of pharmacological interventions targeting aging, as well as in the use of machine learning for analyzing aging-related data. In this new study, researchers Caio Ribeiro, Christopher K. Farmer, João Pedro de Magalhães, and Alex A. Freitas from the University of Kent and University of Birmingham use machine learning methods to analyze data from DrugAge, a database of chemical compounds (including drugs) modulating lifespan in model organisms. “To this end, we created four types of datasets for predicting whether or not a compound extends the lifespan of C. elegans (the most frequent model organism in DrugAge), using four different types of predictive biological features, based on: compound-protein interactions, interactions between compounds and proteins encoded by aging-related genes, and two types of terms annotated for proteins targeted by the compounds, namely Gene Ontology (GO) terms and physiology terms from the WormBase’s Phenotype Ontology.” To analyze these datasets, the researchers used a combination of feature selection methods in a data pre-processing phase and the well-established random forest algorithm for learning predictive models from the selected features. In addition, they interpreted the most important features in the two best models in light of the biology of aging. One noteworthy feature was the GO term “Glutathione metabolic process”, which plays an important role in cellular redox homeostasis and detoxification. The team also predicted the most promising novel compounds for extending lifespan from a list of previously unlabelled compounds. These include nitroprusside, which is used as an antihypertensive medication. “Overall, our work opens avenues for future work in employing machine learning to predict novel life-extending compounds.” Read the full paper: DOI: https://doi.org/10.18632/aging.204866 Corresponding Authors: Caio Ribeiro - C.E.Ribeiro@kent.ac.uk, and Alex A. Freitas - A.A.Freitas@kent.ac.uk Keywords: lifespan-extension compounds, longevity drugs, machine learning, feature selection Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.https://doi.org/10.18632/aging.204866 About Aging-US: Launched in 2009, Aging 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 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 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/ For media inquiries, please contact 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 13, entitled, “MSK1 is required for the beneficial synaptic and cognitive effects of enriched experience across the lifespan.” Positive experiences, such as social interaction, cognitive training and physical exercise, have been shown to ameliorate some of the harms to cognition associated with aging. Animal models of positive interventions, commonly known as environmental enrichment, strongly influence neuronal morphology and synaptic function and enhance cognitive performance. While the profound structural and functional benefits of enrichment have been appreciated for decades, little is known as to how the environment influences neurons to respond and adapt to these positive sensory experiences. In this new study, researchers Lorenzo Morè, Lucia Privitera, Daniel D. Cooper, Marianthi Tsogka, J. Simon C. Arthur, and Bruno G. Frenguelli from the University of Warwick, University of Central Lancashire and University of Dundee show that adult and aged male wild-type mice that underwent a 10-week environmental enrichment protocol demonstrated improved performance in a variety of behavioral tasks, including those testing spatial working and spatial reference memory, and an enhancement in hippocampal long-term potentiation. “Recently, a neuronal protein kinase, mitogen- and stress-activated protein kinase 1 (MSK1) has been identified as being a prime effector within the mammalian brain of the beneficial effects of enrichment in the early phase of the lifespan (birth to 4 months) [34–38].” Aged animals in particular benefitted from enrichment, performing spatial memory tasks at levels similar to healthy adult mice. Many of these benefits, including in gene expression, were absent in mice with a mutation in an enzyme, MSK1, which is activated by BDNF, a growth factor implicated in rodent and human cognition. The researchers conclude that enrichment is beneficial across the lifespan and that MSK1 is required for the full extent of these experience-induced improvements of cognitive abilities, synaptic plasticity and gene expression. “We show that MSK1 retains its importance in converting positive experience into tangible synaptic and cognitive benefits well into old age, reinforcing the aged brain’s capacity to benefit from positive experience, MSK1’s prominence as a key player in the response to enrichment, and its potential as a target for enviromimetics.” Read the full paper: DOI: https://doi.org/10.18632/aging.204833 Corresponding Author: Bruno G. Frenguelli - b.g.frenguelli@warwick.ac.uk Keywords: cognitive reserve, synaptic plasticity, anxiety, spatial memory, LTP Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204833 About Aging-US: Launched in 2009, Aging 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 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 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/ For media inquiries, please contact media@impactjournals.com.

Listen to a blog summary of an editorial published by Aging on July 14, 2023, in Volume 15, Issue 13, entitled, “Cognitive reserve, neuropathology, and progression towards Alzheimer’s disease.” _______________________________________________________________ Why do some individuals maintain cognitive abilities throughout their lifespan and others do not? The better question may be: How can certain individuals preserve their cognitive abilities and delay the onset of dementia despite the presence of significant neuropathologies that would otherwise suggest cognitive decline? This question remains unanswered. “What contributes to this ‘resilience’ [3], that is why some successfully cope with progressive neuropathology while others cannot tolerate the same level of neurodegeneration, is not fully understood.” This unanswered question has driven researchers to consider the idea of “cognitive reserve.” The rather new concept of cognitive reserve suggests that certain factors, such as engaging in education, mental stimulation and challenging activities, can create a buffer against cognitive decline and delay the onset of cognitive impairment or dementia. Researchers continue to study cognitive reserve to better understand its mechanisms and potential implications for maintaining brain health and designing effective interventions. In a new editorial paper, researchers Monica E. Nelson, Ross Andel and Jakub Hort from the University of South Florida’s​​ School of Aging Studies discussed the outcomes, lessons and future implications of their previous 2022 study. The team examined the influence of cognitive reserve proxies on the relationship between brain integrity and cognition. On July 14, 2023, their editorial was published in Aging’s Volume 15, Issue 13, entitled, “Cognitive reserve, neuropathology, and progression towards Alzheimer’s disease.” Full blog - https://aging-us.org/2023/07/exploring-the-impact-of-cognitive-reserve-on-cognitive-resilience/ Editorial paper DOI - https://doi.org/10.18632/aging.204909 Corresponding author - Monica E. Nelson - mnelson10@usf.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204909 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, dementia, neuropathology, Alzheimer’s disease, MRI, volumetry 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 13, entitled, “Cognitive rescue in aging through prior training in rats.” Cognitive decline in spatial memory is seen in aging. Understanding affected processes in aging is vital for developing methods to improve wellbeing. Daily memory persistence can be influenced by events around the time of learning or by prior experiences in early life. Fading memories in young can last longer if a novel event is introduced around encoding, a process called behavioral tagging. In this new study based on this principle, researchers Alexandra Gros and Szu-Han Wang from The University of Edinburgh asked what processes are affected in aging and if prior training can rescue them. “Here we asked if cognitive training in young and mid-life would improve cognitive aging and which elements of the cognitive processes at old age are preferentially protected through such training.” Two groups of aged rats received training in an appetitive delayed matching-to-place task. One of the groups additionally received prior training of the same task in young and in mid-life, constituting a longitudinal study. The results showed long-term memory decline in late aging without prior training. This would reflect affected encoding and consolidation. On the other hand, short-term memory was preserved and novelty at memory reactivation and reconsolidation enabled memory maintenance in aging. Prior training improved cognition by facilitating task performance, strengthening short-term and intermediate memory, and enabling encoding-boosted long-term memory. Learning ability, short-term memories, motor and motivation functions remained intact in older age, suggesting a phase when memory-associated processes are compromised before apparent navigation or learning deficits in advanced aging. Overall, the study's findings suggest a selective impairment in encoding for long-term memory formation in early aging and an additional impairment in consolidation in later aging. “Prior training shows profound benefits in cognitive aging and it can provide a translatable model to simulate human cognition which is built upon lifelong experiences.” DOI - https://doi.org/10.18632/aging.204808 Corresponding author - Szu-Han Wang - s.wang@ed.ac.uk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204808 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, memory consolidation, reconsolidation, memory modulation, lifelong training, cognitive stimulation 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 13, entitled, “Budding uninhibited by benzimidazoles-1 (BUB1) regulates EGFR signaling by reducing EGFR internalization.” EGFR signaling initiates upon ligand binding which leads to activation and internalization of the receptor-ligand complex. In this new study, researchers Shyam Nyati, Grant Young, Corey Speers, Mukesh K. Nyati, and Alnawaz Rehemtulla from the University of Michigan, Henry Ford Health System and Case Western Reserve University evaluated if BUB1 impacted EGFR signaling by regulating EGFR receptor internalization and activation. “We postulate that BUB1 helps in the formation and stabilization of EGFR dimers at the membrane and may regulate endocytosis of activated EGFR into either clathrin dependent (EEA1 coated) or independent (caveolin coated) vesicles thus impacting receptor recycling or degradation and subsequently signaling amplitude and duration [38, 39].” BUB1 was ablated genomically (siRNA) or biochemically (2OH-BNPP1) in cells. EGF ligand was used to initiate EGFR signaling while disuccinimidyl suberate (DSS) was used for cross linking cellular proteins. EGFR signaling was measured by western immunoblotting and receptor internalization was evaluated by fluorescent microscopy (pEGFR (pY1068) colocalization with early endosome marker EEA1). siRNA mediated BUB1 depletion led to an overall increase in total EGFR levels and more phospho-EGFR (Y845, Y1092, and Y1173) dimers while the amount of total EGFR (non-phospho) dimers remained unchanged. BUB1 inhibitor (BUB1i) decreased EGF mediated EGFR signaling including pEGFR Y845, pAKT S473 and pERK1/2 in a time dependent manner. Additionally, BUB1i also reduced EGF mediated pEGFR (Y845) dimers (asymmetric dimers) without affecting total EGFR dimers (symmetric dimers) indicating that dimerization of inactive EGFR is not affected by BUB1. Furthermore, BUB1i blocked EGF mediated EGFR degradation (increase in EGFR half-life) without impacting half-lives of HER2 or c-MET. BUB1i also reduced co-localization of pEGFR with EEA1 positive endosomes suggesting that BUB1 might modulate EGFR endocytosis. “Our data provide evidence that BUB1 protein and its kinase activity may regulate EGFR activation, endocytosis, degradation, and downstream signaling without affecting other members of the receptor tyrosine kinase family.” DOI - https://doi.org/10.18632/aging.204820 Corresponding authors - Shyam Nyati - snyati1@hfhs.org, and Alnawaz Rehemtulla - alnawaz@umich.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204820 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, BUB1, EGFR, cancer, signaling, endocytosis 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 editorial paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 12, entitled, “Advancing screening for cognitive impairment: the memtrax continuous recognition test.” Extensive efforts to find a treatment for Alzheimer’s disease (AD) span over 40 years, with the often-repeated request for better means to assess the principal dysfunction of this disease, memory impairment. Tremendous costs and resources have already been consumed in the development of treatments for this prevalent and well recognized condition, e.g., over $40 billion. These pervasive failures support the urgent need for instruments far superior to those used even in recent studies. The critical impairment in AD is a disorder of neuroplasticity. Thus, cognitive tests which can rapidly, sensitively, frequently, inexpensively, and precisely measure the aspects of memory specifically attacked by AD are principally needed. In this new editorial, researchers J. Wesson Ashford, James O. Clifford and Michael F. Bergeron from Stanford University discuss a continuous recognition test of memory called MemTrax that has been developed to quickly and accurately quantify memory processing, storage and rate of retrieval. “The precision of MemTrax would best improve the specification of the severity of cognitive impairment in early phases of Alzheimer’s disease, a period of this disease when paper and pencil and historical recollection only provide poor estimates of function [4].” Further, MemTrax can precisely assess the rate of change over time with repeat testing. By assessing performance metrics and rate of recognition response, MemTrax can screen for many varieties of cognitive impairment and thus would be an ideal tool for use in the elderly U.S. population for the Medicare Annual Wellness Visit. With a test such as MemTrax or other effective online testing, populations can be broadly and inexpensively assessed for AD-related cognitive impairment and then brought into clinical studies to determine what environmental, genetic, or interventional remedies can prevent further development of AD and the pace and/or extent of cognitive decline. “MemTrax is especially well suited for assessment of very early AD, including early mild cognitive impairment, a time when the focus should be on prevention of AD pathology, not removal of AD pathology.” DOI - https://doi.org/10.18632/aging.204828 Corresponding author - J. Wesson Ashford - ashford@stanford.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204828 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Alzheimer’s disease, memory, online testing, response time, continuous recognition test 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 a groundbreaking study, researchers have unlocked a new frontier in the fight against aging and age-related diseases. The study, conducted by a team of scientists at Harvard Medical School, has published the first chemical approach to reprogram cells to a younger state. Previously, this was only achievable using a powerful gene therapy. On July 12, 2023, researchers Jae-Hyun Yang, Christopher A. Petty, Thomas Dixon-McDougall, Maria Vina Lopez, Alexander Tyshkovskiy, Sun Maybury-Lewis, Xiao Tian, Nabilah Ibrahim, Zhili Chen, Patrick T. Griffin, Matthew Arnold, Jien Li, Oswaldo A. Martinez, Alexander Behn, Ryan Rogers-Hammond, Suzanne Angeli, Vadim N. Gladyshev, and David A. Sinclair from Harvard Medical School, University of Maine and Massachusetts Institute of Technology (MIT) published a new research paper in Aging, titled, “Chemically induced reprogramming to reverse cellular aging.” The team's findings build upon the discovery that the expression of specific genes, called Yamanaka factors, could convert adult cells into induced pluripotent stem cells (iPSCs). This Nobel Prize-winning discovery raised the question of whether it might be possible to reverse cellular aging without causing cells to become too young and turn cancerous. In this new study, the researchers screened for molecules that could, in combination, reverse cellular aging and rejuvenate human cells. They developed high-throughput cell-based assays to distinguish young cells from old and senescent cells, including transcription-based aging clocks and a real-time nucleocytoplasmic protein compartmentalization (NCC) assay. In an exciting discovery, the team has identified six chemical cocktails that restore NCC and genome-wide transcript profiles to youthful states and reverse transcriptomic age in less than a week. The Harvard researchers previously demonstrated that it is indeed possible to reverse cellular aging without uncontrolled cell growth by virally-introducing specific Yamanaka genes into cells. Studies on the optic nerve, brain tissue, kidney, and muscle have shown promising results, with improved vision and extended lifespan observed in mice and, recently, a report of improved vision in monkeys. The implications of this new discovery are far-reaching, opening avenues for regenerative medicine and, potentially, whole-body rejuvenation. By developing a chemical alternative to age reversal via gene therapy, this research could revolutionize the treatment of aging, injuries and age-related diseases and offers the potential for lower costs and shorter timelines in development. On the heels of positive results in reversing blindness in monkeys in April 2023, preparations for human clinical trials of the lab’s age reversal gene therapy are in progress. “Until recently, the best we could do was slow aging. New discoveries suggest we can now reverse it,” said David A. Sinclair, A.O., Ph.D., Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School and lead scientist on the project. “This process has previously required gene therapy, limiting its widespread use.” The team at Harvard envisions a future where age-related diseases can be effectively treated, injuries can be repaired more efficiently, and the dream of whole-body rejuvenation becomes a reality. “This new discovery offers the potential to reverse aging with a single pill, with applications ranging from improving eyesight to effectively treating numerous age-related diseases,” Sinclair said. Press Release: https://www.aging-us.com/news_room/NEW-STUDY-Discovery-of-Chemical-Means-to-Reverse-Aging-and-Restore-Cellular-Function DOI: https://doi.org/10.18632/aging.204896 Corresponding Author: David A. Sinclair - david_sinclair@hms.harvard.edu Visit https://www.Aging-US.com​​ and connect with us on social media. MEDIA@IMPACTJOURNALS.COM

New research continues to illuminate the far-reaching implications of the gut microbiome and its crucial role in our overall health. The term “gut dysbiosis” refers to an imbalance of healthy and unhealthy microbes in the gastrointestinal tract. Repercussions of gut dysbiosis are not only limited to innocuous discomfort—it can lead to immune dysregulation and trigger a cascade of various disease states. In a new editorial paper, researchers Chun-Che Hung, Kristi M. Crowe-White and Ian M. McDonough from Chang Gung University and The University of Alabama discuss the relationship between gut dysbiosis and neurocognitive disorders such as Alzheimer’s disease (AD). Their editorial was published in Aging’s Volume 15, Issue 12, on June 19, 2023, entitled, “A seed and soil model of gut dysbiosis in Alzheimer’s disease.” “[…] recent research has demonstrated a crucial role of gut microbiota in the etiopathogenesis of AD [Alzheimer’s disease] that offers a new window into possible origins and consequences of AD through interactions between gut microbiota and the central nervous system, known as the ‘microbiota-gutbrain axis’ [1].” Full blog - https://aging-us.org/2023/07/can-a-leaky-gut-lead-to-alzheimers-disease/ Paper DOI - https://doi.org/10.18632/aging.204840 Corresponding author - Ian M. McDonough - immcdonough@ua.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204840 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Alzheimer’s disease, neurocognitive disorders, gut-brain axis, gut microbiota, dysbiosis 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