Aging-US

Impact Journals (Aging's publisher) will be participating as an exhibitor at the American Association for Cancer Research (AACR) Annual Meeting 2023 from April 14-19 at the Orange County Convention Center in Orlando, Florida. This year, the AACR meeting theme is: “Advancing the Frontiers of Cancer Science and Medicine.” Impact Journals publishes scholarly journals in the biomedical sciences with a focus on all areas of cancer and aging research. Aging is one of the most prominent journals published by Impact Journals. Aging’s 2021 Impact Factor is 5.955. This number has increased from 2020’s 5.682. Visit booth No. 2642 at the AACR Annual Meeting 2023 to connect with members of the Aging team. Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, aacr, conference, meeting, annual meeting, cancer research 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 6, entitled, “Potential reversal of biological age in women following an 8-week methylation-supportive diet and lifestyle program: a case series.” In this new study, researchers Kara N. Fitzgerald, Tish Campbell, Suzanne Makarem, and Romilly Hodges from the Institute for Functional Medicine, Virginia Commonwealth University and the American Nutrition Association reported on a case series of six women who completed a methylation-supportive diet and lifestyle program designed to impact DNA methylation and measures of biological aging. “The modifiable lifestyle intervention used by participants in this case series was first investigated in a pilot clinical trial in which participants (all men between the ages of 50-72 years) reduced their biological age by an average of 3.23 years as compared to controls [7]. The case series reported on herein was conducted to further the investigation of a modifiable lifestyle intervention that was largely the same in other populations; importantly in women.” The team carried out an intervention consisting of an eight-week program. This program included guidance on diet, sleep, exercise, and relaxation, supplemental probiotics and phytonutrients and nutritional coaching. DNA methylation and biological age analysis (Horvath DNAmAge clock (2013), normalized using the SeSAMe pipeline [a]) was conducted on blood samples at baseline and at the end of the eight-week period. Five of the six participants exhibited a biological age reduction of between 1.22 and 11.01 years from their baseline biological age. There was a statistically significant (p=.039) difference in the participants' mean biological age before (55.83 years) and after (51.23 years) the 8-week diet and lifestyle intervention, with an average decrease of 4.60 years. The average chronological age at the start of the program was 57.9 years and all but one participant had a biological age younger than their chronological age at the start of the program, suggesting that biological age changes were unrelated to disease improvement and instead might be attributed to underlying aging mechanisms. “This case series of women participants extends the previous pilot study of this intervention in men, indicating that favorable biological age changes may be achievable in both sexes. In addition, the investigation of otherwise-healthy individuals, rather than those with diagnosed disease, suggests an influence directly on underlying mechanisms of aging instead of disease-driven aging.” DOI: https://doi.org/10.18632/aging.204602 Corresponding Author: Kara N. Fitzgerald - kf@drkarafitzgerald.com Keywords: DNA methylation, epigenetic aging, lifestyle, biological clock Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204602 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 6, entitled, “Cellular senescence and disrupted proteostasis induced by myotube atrophy are prevented with low-dose metformin and leucine cocktail.” Aging coincides with the accumulation of senescent cells within skeletal muscle that produce inflammatory products, known as the senescence-associated secretory phenotype, but the relationship of senescent cells to muscle atrophy is unclear. Previously, researchers found that a metformin + leucine (MET+LEU) treatment had synergistic effects in aged mice to improve skeletal muscle structure and function during disuse atrophy. In this new study, researchers Jonathan J. Petrocelli, Naomi M.M.P. de Hart, Marisa J. Lang, Elena M. Yee, Patrick J. Ferrara, Dennis K. Fix, Amandine Chaix, Katsuhiko Funai, and Micah J. Drummond from the University of Utah aimed to determine the mechanisms by which MET+LEU exhibits muscle atrophy protection in vitro and if this occurs through cellular senescence. “The purpose of this study was to identify the skeletal muscle cell-intrinsic effects of MET+LEU during an atrophy stimulus. Secondarily, we sought to determine the possible mechanisms underlying MET+LEU action on skeletal muscle cells with an emphasis on cellular senescence.” C2C12 myoblasts differentiated into myotubes were used to determine MET+LEU mechanisms during atrophy. Additionally, aged mouse single myofibers and older human donor primary myoblasts were individually isolated to determine the translational potential of MET+LEU on muscle cells. MET+LEU (25 + 125 μM) treatment increased myotube differentiation and prevented myotube atrophy. Low concentration (0.1 + 0.5 μM) MET+LEU had unique effects to prevent muscle atrophy and increase transcripts related to protein synthesis and decrease transcripts related to protein breakdown. Myotube atrophy resulted in dysregulated proteostasis that was reversed with MET+LEU and individually with proteasome inhibition (MG-132). Inflammatory and cellular senescence transcriptional pathways and respective transcripts were increased following myotube atrophy yet reversed with MET+LEU treatment. Dasatinib + quercetin (D+Q) senolytic prevented myotube atrophy similar to MET+LEU. Finally, MET+LEU prevented loss in myotube size in alternate in vitro models of muscle atrophy as well as in aged myofibers while, in human primary myotubes, MET+LEU prevented reductions in myonuclei fusion. These data support that MET+LEU has skeletal muscle cell-autonomous properties to prevent atrophy by reversing senescence and improving proteostasis. “In conclusion, this study provides evidence of a possible link between cellular senescence and disrupted proteostasis that is targeted by MET+LEU in muscle cells to reverse the muscle atrophy phenotype.” DOI: https://doi.org/10.18632/aging.204600 Corresponding Author: Micah J. Drummond - micah.drummond@hsc.utah.edu Keywords: skeletal muscle atrophy, inflammation, senolytic, AMPK, protein breakdown 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/ MEDIA@IMPACTJOURNALS.COM

A new editorial paper was published in Aging (Aging-US) Volume 15, Issue 5, entitled, “Senescence and extracellular vesicles: novel partners in vascular amyloidosis.” In their editorial, researchers Meredith Whitehead, Marco Antonazzi and Catherine M. Shanahan from King’s College London discussed amyloidosis—a prevalent age-associated pathology caused by the accumulation of fibrous, insoluble protein fibrils in tissues. The most common human amyloid is aortic medial amyloid (AMA), caused by aggregation of a 50-amino acid peptide called medin, which is cleaved by an unknown mechanism from its parent protein, milk fat globulin EGF-factor 8 (MFGE8). Medin is present in the vessel wall of 97% of Caucasians aged over 50- years ,yet despite its prevalence in the ageing population there is a very limited understanding of the mechanisms driving AMA. “Despite several forms of amyloidosis, including AMA and Alzheimer’s disease (AD), being frequently associated with ageing, there has been limited research to date on the effect of cellular ‘ageing’, termed senescence, on amyloidosis.” The novel data presented in the paper by Whitehead et al. provides evidence that vascular smooth muscle cell (VSMC)-derived small extracellular vesicles (sEVs) are key mediators of medin accumulation in the vessel wall. In addition, the authors identify, for the first time, a role for cellular senescence in triggering amyloidosis via changes in sEVs and extracellular matrix (ECM) composition. Thus, this study not only advances our understanding of how AMA is formed but uncovers potential therapeutic targets for mitigating the detrimental effects of amyloidosis on tissue function. “Further work is now required to understand the relationships between cellular ageing pathways, different forms of amyloidosis and potentially other ageing pathologies with shared mechanisms, such as vascular calcification, that often occur concomitantly within the aged ECM.” Full Editorial: DOI: https://doi.org/10.18632/aging.204571 Corresponding Author: Catherine M. Shanahan -cathy.shanahan@kcl.ac.uk Keywords: amyloid, smooth muscle cells, senescence, extracellular vesicles, medin Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204571 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 (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