Aging-US

A new editorial paper was published in Aging (Aging-US) Volume 15, Issue 5, entitled, “Parsing chronological and biological age effects on vaccine responses.” Researchers Chris P. Verschoor and George A. Kuchel from Health Sciences North Research Institute in Ontario, Canada, began this editorial by writing that the COVID-19 pandemic illustrated that older age, particularly when accompanied by common chronic illnesses of aging, is arguably the most significant population attributable factor for severe outcomes of acute respiratory infection, including the risk of hospitalization, disability and death. “In the absence of widely available and highly effective treatments, vaccines remain our most powerful tool to help overcome this vulnerability through the prevention of primary infection, and far more importantly, by improving clinical outcomes once infection does take place.” In the case of SARS-CoV-2, vaccine effectiveness (VE) against hospitalization was remarkable for dominant strains prior to omicron, whereas for influenza or Streptococcus pneumoniae VE ranges from 80% to <10%, depending on the season and infecting strain/serotype. Nonetheless, for all three pathogens VE decreases with age, which is caused by deficiencies in the capacity of older adults’ immune systems to mount productive and persistent antibody and/or cell-mediated responses to the vaccine. Given that extremely large, costly and typically lengthy clinical trials are often required to estimate VE reliably, the vast majority of human vaccine studies assess immune correlates of protection as a proxy to VE. For these studies, antibody related parameters such as neutralization capacity are most commonly employed since they are generally simpler from a technical standpoint and many have been rigorously standardized. “Although informative, cross-sectional studies comparing immune parameters across age groups to understand ‘immune aging’ risk ignore the degree to which departures from healthy aging might contribute.” Full Editorial: DOI: https://doi.org/10.18632/aging.204572 Corresponding Author: Chris P. Verschoor - cverschoor@hsnri.ca Keywords: biological age, frailty, vaccination, influenza Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204572 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Blog summary of a research paper published in Volume 15, Issue 5 of Aging (Aging-US): “Cellular senescence with SASP in periodontal ligament cells triggers inflammation in aging periodontal tissue.” _____________________________________________ Repercussions of poor dental health aren’t limited to mere social stigmas. Poor dental health can impart serious consequences on an individual’s overall health. Periodontal disease broadly refers to any disease that affects the gums and the surrounding tissues that support the teeth, including the periodontal ligament (PDL) and alveolar bone. Periodontal disease can increase the risk of heart disease, stroke and diabetes by allowing bacteria to enter the bloodstream, causing inflammation and organ damage. Periodontitis is a more advanced stage of periodontal disease. It is thought to be the most common infectious disease in the United States—affecting more than 40% of adults over 30 years old. Previous research has suggested that aging is a significant risk factor for periodontitis, although the underlying mechanisms are unclear. “The direct cause of periodontitis is periodontopathic bacteria, while various environmental factors affect the severity of periodontitis. Previous epidemiological studies have shown positive correlations between aging and periodontitis. However, whether and how aging is linked to periodontal health and disease in biological processes is poorly understood.” Full blog - https://aging-us.org/2023/03/a-promising-approach-to-preventing-periodontitis/ DOI - https://doi.org/10.18632/aging.204569 Corresponding author - Motozo Yamashita - yamashita.motozou.dent@osaka-u.ac.jp Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204569 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, periodontitis, periodontal ligament, SASP, microRNAs, SIRT1 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 5, entitled, “Age-related methylation changes in the human sperm epigenome.” Advanced paternal age is associated with increased risks for reproductive and offspring medical problems. Accumulating evidence suggests age-related changes in the sperm epigenome as one underlying mechanism. In a recent study, researchers Laura Bernhardt, Marcus Dittrich, Andreas Prell, Ramya Potabattula, Charis Drummer, Rüdiger Behr, Thomas Hahn, Martin Schorsch, Tobias Müller, and Thomas Haaf from Julius Maximilians University, Partner Site Göttingen and Fertility Center Wiesbaden performed reduced representation bisulfite sequencing (RRBS) on 73 sperm samples of males attending a fertility center in Germany. “[...] we identified 1,162 (74%) regions which were significantly (FDR-adjusted) hypomethylated and 403 regions (26%) being hypermethylated with age.” There were no significant correlations with paternal BMI, semen quality, or ART outcome. The majority (1,152 of 1,565; 74%) of age-related differentially methylated regions (ageDMRs) were located within genic regions, including 1,002 genes with symbols. Hypomethylated ageDMRs were closer to transcription start sites than hypermethylated DMRs, half of which reside in gene-distal regions. In this and conceptually related genome-wide studies, so far 2,355 genes have been reported with significant sperm ageDMRs, however most (90%) of them in only one study. The 241 genes which have been replicated at least once showed significant functional enrichments in 41 biological processes associated with development and the nervous system and in 10 cellular components associated with synapses and neurons. This supports the hypothesis that paternal age effects on the sperm methylome affect offspring behavior and neurodevelopment. The researchers found it interesting to note that sperm ageDMRs were not randomly distributed throughout the human genome; chromosome 19 showed a highly significant twofold enrichment with sperm ageDMRs. Although the high gene density and CpG content have been conserved, the orthologous marmoset chromosome 22 did not appear to exhibit an increased regulatory potential by age-related DNA methylation changes. “Collectively, our data support the conclusion that age-induced methylation changes in the sperm epigenome contribute to the increased offspring disease susceptibility for neurodevelopmental disorders.” DOI: https://doi.org/10.18632/aging.204546 Corresponding Author: Thomas Haaf - thomas.haaf@uni-wuerzburg.de Keywords: ART outcome, DNA methylation, male germ cells, paternal age effect, human sperm epigenome Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204546 Keywords - aging, ART outcome, DNA methylation, male germ cells, paternal age effect, human sperm epigenome About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ MEDIA@IMPACTJOURNALS.COM

Ariel K. Frame, PhD Candidate in the Neuroscience program at Western University, London, Canada, discusses a research paper he co-authored that was published by Aging (Aging-US) in Volume 15, Issue 4, entitled, “Aging and memory are altered by genetically manipulating lactate dehydrogenase in the neurons or glia of flies.” DOI - https://doi.org/10.18632/aging.204565 Corresponding authors - Ariel K. Frame - aframe@uwo.ca, and Robert C. Cumming - rcummin5@uwo.ca Abstract The astrocyte-neuron lactate shuttle hypothesis posits that glial-generated lactate is transported to neurons to fuel metabolic processes required for long-term memory. Although studies in vertebrates have revealed that lactate shuttling is important for cognitive function, it is uncertain if this form of metabolic coupling is conserved in invertebrates or is influenced by age. Lactate dehydrogenase (Ldh) is a rate limiting enzyme that interconverts lactate and pyruvate. Here we genetically manipulated expression of Drosophila melanogaster lactate dehydrogenase (dLdh) in neurons or glia to assess the impact of altered lactate metabolism on invertebrate aging and long-term courtship memory at different ages. We also assessed survival, negative geotaxis, brain neutral lipids (the core component of lipid droplets) and brain metabolites. Both upregulation and downregulation of dLdh in neurons resulted in decreased survival and memory impairment with age. Glial downregulation of dLdh expression caused age-related memory impairment without altering survival, while upregulated glial dLdh expression lowered survival without disrupting memory. Both neuronal and glial dLdh upregulation increased neutral lipid accumulation. We provide evidence that altered lactate metabolism with age affects the tricarboxylic acid (TCA) cycle, 2-hydroxyglutarate (2HG), and neutral lipid accumulation. Collectively, our findings indicate that the direct alteration of lactate metabolism in either glia or neurons affects memory and survival but only in an age-dependent manner. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204565 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, astrocyte-neuron lactate shuttle (ANLS), lactate, lactate dehydrogenase, dLdh, Drosophila melanogaster, glia, long-term memory, courtship conditioning 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 5, entitled, “Senescence-associated exosomes transfer miRNA-induced fibrosis to neighboring cells.” Radiation-induced fibrosis is a common side effect of radiotherapy, which is the most common treatment for cancer. However, radiation also causes p53-mediated cell cycle arrest, prolonged expression of p21, and the development of senescence in normal cells that reside in irradiated tissues. Bone marrow-derived mesenchymal stem cells (MSCs) accumulate in primary tumor sites because of their natural tropism for inflammatory and fibrotic tissues. MSCs are extremely sensitive to low doses of ionizing radiation and acquire senescence as a result of bystander radiation effects. Senescent cells remain metabolically active but develop a potent senescence-associated secretory phenotype (SASP) that correlates to hyperactive secretion of cytokines, pro-fibrotic growth factors, and exosomes (EXOs). Integrative pathway analysis has highlighted that radiation-induced senescence significantly enriched cell-cycle, extracellular matrix, transforming growth factor-β (TGF-β) signaling, and vesicle-mediated transport genes in MSCs. EXOs are cell-secreted nanovesicles (a subclass of small extracellular vesicles) that contain biomaterials—proteins, RNAs, microRNAs (miRNAs)—that are critical in cell-cell communication. miRNA content analysis of secreted EXOs further revealed that radiation-induced senescence uniquely altered miRNA profiles. “In fact, several of the standout miRNAs directly targeted TGF-β or downstream genes.” In this new study, researchers Amy H. Lee, Deepraj Ghosh, Ivy L. Koh, and Michelle R. Dawson from Brown University further treated normal MSCs with senescence-associated EXOs (SA-EXOs) to examine bystander effects of radiation-induced senescence. The researchers found that these modulated genes were related to TGF-β pathway and elevated both alpha smooth muscle actin (protein increased in senescent, activated cells) and Ki-67 (proliferative marker) expression in SA-EXO treated MSCs compared to untreated MSCs. They revealed that SA-EXOs possess unique miRNA content that influence myofibroblast phenotypes via TGF-β pathway activation. This highlights that SA-EXOs are potent SASP factors that play a large role in cancer-related fibrosis. “Our integrated omics and EXO microarray analyses show that senescent MSCs possess differential transcriptional genes and secrete vesicles that contain unique post-transcriptional cargo. We subsequently demonstrated that these EXO miRNAs can play important roles in cell-cell communication during disease progression.” Paper: DOI: https://doi.org/10.18632/aging.204539 Corresponding Author: Michelle R. Dawson - michelle_dawson@brown.edu Keywords: radiation-induced senescence, exosomes (EXOs), microRNA (miRNA), transforming growth factor-β (TGF-β), mesenchymal stem cells (MSCs) About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 5, entitled, “AAV1.NT-3 gene therapy prevents age-related sarcopenia.” Sarcopenia is progressive loss of muscle mass and strength occurring during normal aging with significant consequences on the quality of life for elderly. Neurotrophin 3 (NT-3) is an important autocrine factor supporting Schwann cell survival and differentiation and stimulating axon regeneration and myelination. NT-3 is involved in the maintenance of neuromuscular junction (NMJ) integrity, restoration of impaired radial growth of muscle fibers through activation of the Akt/mTOR pathway. In this new study, researchers Burcak Ozes, Lingying Tong, Morgan Myers, Kyle Moss, Alicia Ridgley, and Zarife Sahenk from Nationwide Children’s Hospital and The Ohio State University used a triple muscle-specific creatine kinase (tMCK) promoter to restrict NT-3 expression to the skeletal muscle and self-complimentary adeno-associated virus serotype 1 (scAAV1) as vector to assess the therapeutic efficacy of AAV1.NT-3 in wild type-aged C57BL/6J mice, a model for natural aging and sarcopenia. “Quantitative histopathologic parameters served to address age-related changes in muscle, peripheral nerve and NMJ.” The treatment efficacy was assessed at 6 months post-injection using run to exhaustion and rotarod tests, in vivo muscle contractility assay, and histopathological studies of the peripheral nervous system, including NMJ connectivity and muscle. AAV1.NT-3 gene therapy in WT-aged C57BL/6 mice resulted in functional and in vivo muscle physiology improvements, supported by quantitative histology from muscle, peripheral nerves and NMJ. Hindlimb and forelimb muscles in the untreated cohort showed the presence of a muscle- and sex-dependent remodeling and fiber size decrease with aging, which was normalized toward values obtained from 10 months old WT mice with treatment. The molecular studies assessing the NT-3 effect on the oxidative state of distal hindlimb muscles, accompanied by western blot analyses for mTORC1 activation were in accordance with the histological findings. “When considering the burden of sarcopenia on the lifestyle of elderly, and on the healthcare system, we believe this preclinical study is providing strong support for AAV.NT-3 gene therapy in the successful management of sarcopenia, as a serious and plausible option in the future.” DOI: https://doi.org/10.18632/aging.204577 Corresponding Author: Zarife Sahenk - zarife.sahenk@nationwidechildrens.org Keywords: sarcopenia, gene therapy, aging, NT-3, muscle remodeling Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204577 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

Aging (Aging-US) published a new editorial paper in Volume 15, Issue 4, entitled, “Cognitive aging and dementia prevention: the time for psychology?” Modifiable risk and protective factors (e.g. engaging in active lifestyles and avoiding alcohol or smoking amongst others) are seen as key agents for dementia prevention, and they also exert an important effect on cognitive trajectories of non-demented older adults. In this new editorial, researchers David Bartrés-Faz, Cristina Solé-Padullés and Natalie L. Marchant from the University of Barcelona discuss recent research that has begun to identify psychological processes that confer relative risk and protection. “For example, repetitive negative thinking (RNT), a cognitive process defined by selfrelevant, persistent thoughts that elaborate on negative themes, has been associated with greater burden of typical Alzheimer’s disease (AD) pathological brain markers and accelerated cognitive decline over time [3].” In contrast, self-reflection, as well as purpose in life and other components of psychological well being, may help to maintain cognition and boost cognitive resilience against neuropathological burden. The possibility of incorporating psychological elements as key players in affecting one of the most important public health issues of the century opens a window of great therapeutic opportunity, particularly because fundamental psychological processes are at the core of cognitive-behavioral interventions that may help reduce dementia risk. However, for this emergent area to develop and wield maximum benefit, major unanswered questions need to be addressed. In their editorial, the researchers highlight three main areas for future research. “In summary, we propose that with momentum gathering, now is the time for psychology to make important contributions to cognitive ageing and dementia prevention research.” Full Paper: DOI: https://doi.org/10.18632/aging.204562 Corresponding Author: David Bartrés-Faz - dbartres@ub.edu Keywords: cognitive aging, psychological factors, dementia, prevention Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204562 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Blog summary of a research paper published in Aging (Aging-US) Volume 15, Issue 4: "Aging and memory are altered by genetically manipulating lactate dehydrogenase in the neurons or glia of flies." __________________________________________________________ The brain is a complex organ responsible for many critical functions, including the formation and retrieval of our memories. As we age, the brain undergoes changes that can affect cognitive abilities, including our memory. Understanding the mechanisms that underlie these changes is critical for developing therapies for age-related cognitive decline. “Over the last two decades there has been growing recognition that lactate, the end product of glycolysis, serves many functions, including acting as a source of energy, a signaling molecule, and even as an epigenetic regulator.” Lactate is a molecule that is produced during the metabolism of glucose in the body. It is a byproduct of anaerobic metabolism, which occurs when there is insufficient oxygen supply to meet the energy demands of the body. Lactate can be used as an energy source by some cells, such as the heart and skeletal muscles, and it can also be transported to the liver where it can be converted back into glucose. Lactate dehydrogenase (LDH), on the other hand, is an enzyme that catalyzes the conversion of pyruvate to lactate (the reverse reaction of lactate production) and is also involved in other metabolic processes. This enzyme is found in many tissues of the body, including the heart, liver and skeletal muscles, and is released into the bloodstream when tissues are damaged. LDH is often used as a diagnostic marker for various medical conditions, such as heart attacks, liver disease and certain cancers. High levels of LDH in the blood may indicate tissue damage or cell death, while low levels may indicate a deficiency in the enzyme. Blog - https://aging-us.org/2023/03/fruit-flies-shed-new-light-on-memory-and-aging/ DOI - https://doi.org/10.18632/aging.204565 Corresponding authors - Ariel K. Frame - aframe@uwo.ca, and Robert C. Cumming - rcummin5@uwo.ca Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204565 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ MEDIA@IMPACTJOURNALS.COM

Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) published a new research paper in Volume 15, Issue 4, entitled, “Isoform-specific effects of neuronal repression of the AMPK catalytic subunit on cognitive function in aged mice.” AMP-activated protein kinase (AMPK) functions as a molecular sensor that plays a critical role in maintaining cellular energy homeostasis. Dysregulation of the AMPK signaling has been linked to synaptic failure and cognitive impairments. In a recent study, researchers Xueyan Zhou, Wenzhong Yang, Xin Wang, and Tao Ma from Wake Forest University School of Medicine demonstrated abnormally increased AMPK activity in the hippocampus of aged mice. The kinase catalytic subunit of AMPK exists in two isoforms α1 and α2, and their specific roles in aging-related cognitive deficits are unknown. “Taking advantage of the unique transgenic mice (AMPKα1/α2 cKO) recently developed by our group, we investigated how isoform-specific suppression of the neuronal AMPKα may contribute to the regulation of cognitive and synaptic function associated with aging.” The team found that aging-related impairment of long-term object recognition memory was improved with suppression of AMPKα1 but not AMPKα2 isoform. Moreover, aging-related spatial memory deficits were unaltered with suppression of either AMPKα isoform. Biochemical experiments showed that the phosphorylation levels of the eukaryotic initiation factor 2 α subunit (eIF2α) were specifically decreased in the hippocampus of the AMPKα1 cKO mice. They further performed large-scale unbiased proteomics analysis and revealed identities of proteins whose expression is differentially regulated with AMPKα isoform suppression. These novel findings may provide insights into the roles of AMPK signaling pathway in cognitive aging. “In summary, the current study reported that suppression of neuronal AMPKα1 isoform can improve aging-related impairments of long-term recognition memory.” Full Paper: DOI: https://doi.org/10.18632/aging.204554 Corresponding Author: Tao Ma - tma@wakehealth.edu Keywords: AMPK, aging, protein synthesis, learning and memory, proteomics Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204554 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

Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) published a new review paper in Volume 15, Issue 4, entitled, “Cellular senescence: when growth stimulation meets cell cycle arrest.” In this review, researcher Mikhail V. Blagosklonny, M.D., Ph.D., from Roswell Park Comprehensive Cancer Center discusses cellular senescence—a natural process that occurs as cells age and eventually stop dividing. Recent research has revealed that cellular senescence can also be triggered by hypertrophy and hyperfunctions. “At the very moment of cell-cycle arrest, the cell is not senescent yet. For several days in cell culture, the arrested cell is acquiring a senescent phenotype. What is happening during this geroconversion? Cellular enlargement (hypertrophy) and hyperfunctions (lysosomal and hyper-secretory) are hallmarks of geroconversion.” In his comprehensive review paper, Dr. Blagosklonny explores the complex relationship between growth stimulation and cell cycle arrest in cellular senescence. He discusses the various mechanisms that can lead to senescence, markers of senescence and geroconversion, and the importance of understanding these mechanisms and markers in the development of anti-aging drugs. “The same pathways that drive geroconversion are involved in organismal aging and age-related diseases. The same drugs that slow down geroconversion also extend lifespan, as tested in animals so far. Targets of gerostatics (e.g., mTOR, PI3K) are involved in aging of animals from worms to mammals. Therefore, gerostatics are anti-aging drugs. The model of geroconversion is useful to discover anti-aging drugs.” Dr. Blagosklonny is a renowned expert in the field of aging research. He has focused on the molecular mechanisms of aging, the hyperfunction theory of aging and the development of new drugs to combat age-related diseases. Dr. Blagosklonny’s research, perspectives and reviews have made significant contributions to our understanding of aging. Full Paper: DOI: https://doi.org/10.18632/aging.204543 Corresponding Author: Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.com Keywords: rapamycin, mTOR, hyperfunction theory of aging, cell volume and enlargement, gerogenic conversion Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204543