Aging-US

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 14, entitled, “A novel theory of ageing independent of damage accumulation.” The underlying cause or causes of aging are an enduring mystery, but in 1977 Kirkwood postulated that organisms might gain a fitness advantage by reducing investment in somatic maintenance if this allowed them to invest more resources in more crucial processes such as reproduction. The accumulation of somatic damage was therefore inevitable, and his disposable soma theory has dominated gerontology ever since. However, as our understanding of aging increases, it is becoming increasingly difficult to align all the aspects of aging with accumulating damage. For example, mutations that increase damage accumulation can also increase longevity, while rejuvenation revelations such as parabiosis and Yamanaka factors indicate that youthfulness can be regained without high energetic cost and despite high levels of damage. In their new editorial, researchers James Wordsworth and Daryl Shanley from Newcastle University discuss their recently published paper on selective destruction theory (SDT). SDT suggests a mechanism of aging which is both independent of accumulating damage and consistent with epigenetic rejuvenation. The authors used agent-based modeling to describe how aging could undergo positive selection independent of energetic costs. “The mechanism of selective destruction is currently theoretical. In our most developed model, we demonstrated that if slow cells induced epigenetic changes in faster cells causing their metabolism to slow (rather than killing them) it not only reduced unnecessary cell death, but also further reduced the likelihood of overactivity disorders by preventing the spread of fast cells.” DOI - https://doi.org/10.18632/aging.204956 Corresponding author - James Wordsworth - James.Wordsworth2@newcastle.ac.uk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204956 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, ageing, evolution, damage, cell competition, metabolic slowdown 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 14, entitled, “Inhibiting NLRP3 signaling in aging podocytes improves their life- and health-span.” The decrease in the podocyte’s lifespan and health-span that typify healthy kidney aging cause a decrease in their normal structure, physiology and function. The ability to halt and even reverse these changes becomes clinically relevant when disease is superimposed on an aged kidney. NLRP3 [nod-like receptor protein 3] expression is increased in podocytes of mice with advanced age and contributes to their damage. “However, the functional consequence of increased levels of NLRP3 in aged podocytes is unknown.” In this new study, researchers Natalya Kaverina, R. Allen Schweickart, Gek Cher Chan, Joseph C. Maggiore, Diana G. Eng, Yuting Zeng, Sierra R. McKinzie, Hannah S. Perry, Adilijiang Ali, Christopher O’Connor, Beatriz Maria Veloso Pereira, Ashleigh B. Theberge, Joshua C. Vaughan, Carol J. Loretz, Anthony Chang, Neil A. Hukriede, Markus Bitzer, Jeffrey W. Pippin, Oliver Wessely, and Stuart J. Shankland from the University of Washington, Cleveland Clinic Foundation, National University Hospital Singapore, University of Pittsburgh, University of Michigan, and the University of Chicago hypothesized that reducing NLRP3 signaling earlier at middle-age improves overall podocyte health and slows down healthy podocyte aging in mice. “To this end, we performed a comprehensive analysis of inflammasome signaling including pharmacological and genetic NLRP3 loss-of-function approaches.” RNA-sequencing of podocytes from middle-aged mice showed an inflammatory phenotype with increases in the NLRP3 inflammasome, signaling for IL2/Stat5, IL6 and TNF, interferon gamma response, allograft rejection and complement, consistent with inflammaging. Furthermore, injury-induced NLRP3 signaling in podocytes was further augmented in aged mice compared to young ones. The NLRP3 inflammasome (NLRP3, Caspase-1, IL1β IL-18) was also increased in podocytes of middle-aged humans. Higher transcript expression for NLRP3 in human glomeruli was accompanied by reduced podocyte density and increased global glomerulosclerosis and glomerular volume. Pharmacological inhibition of NLRP3 with MCC950, or gene deletion, reduced podocyte senescence and the genes typifying aging in middle-aged mice, which was accompanied by an improved podocyte lifespan and health-span. Moreover, modeling the injury-dependent increase in NLRP3 signaling in human kidney organoids confirmed the anti-senescence effect of MC9950. Finally, NLRP3 also impacted liver aging. “In summary, our results demonstrate for the first time that aging podocytes acquire an inflammatory phenotype, which include the NLRP3 inflammasome and which is consistent with inflammaging.” DOI - https://doi.org/10.18632/aging.204897 Corresponding authors - Oliver Wessely - wesselo@ccf.org, and Stuart J. Shankland - stuartjs@uw.edu Keywords - aging, kidney, podocyte, NLRP3 inflammasome, reporter 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: 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/ For media inquiries, please contact: MEDIA@IMPACTJOURNALS.COM

A new research perspective was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 14, entitled, “Towards disease-oriented dosing of rapamycin for longevity: does aging exist or only age-related diseases?” In his new research perspective, Dr. Mikhail V. Blagosklonny from Roswell Park Comprehensive Cancer Center discusses aging and rapamycin (Sirolimus) — the only drug that consistently extends life span in countless animal studies in all species tested. He writes that individuals taking rapamycin and those not taking it will ultimately succumb to age-related diseases. However, if administered in disease-oriented dosages for an extended period of time, individuals taking rapamycin may experience a delayed onset of such diseases, and live longer. “The goal is to delay a particular disease that is expected to be life-limiting in a particular person.” Age-related diseases, quasi-programmed during development, progress at varying rates in different individuals. Rapamycin is a prophylactic anti-aging drug that decelerates early development of age-related diseases. Dr. Blagosklonny further discusses the hyperfunction theory of quasi-programmed diseases, which challenges the need for the traditional concept of aging itself. “I emphasize that aging is not programmed but, in contrast, quasi-programmed. Quasi means pseudo; seemingly; apparently but not really. Some scientists deliberately represent hyperfunction theory as theory of programmed aging. It’s the opposite. Quasi-program is a continuation of a real program. Quasi-program has no intent, no purpose and it is always harmful.” DOI - https://doi.org/10.18632/aging.204920 Corresponding author - Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204920 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, mTOR, hyperfunction, lifespan, health span, cancer, Alzheimer’s disease 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 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