Aging-US

A new research paper was published in Aging (Aging-US) Volume 15, Issue 7, entitled, “Viral vector-mediated upregulation of serine racemase expression in medial prefrontal cortex improves learning and synaptic function in middle age rats.” An age-associated decrease in N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic function contributes to impaired synaptic plasticity and is associated with cognitive impairments. Levels of serine racemase (SR), an enzyme that synthesizes D-serine, an NMDAR co-agonist, decline with age. In this new study, researchers Brittney Yegla, Asha Rani and Ashok Kumar from the University of Florida’s McKnight Brain Institute predicted that enhancing NMDAR function via increased SR expression in middle age (when subtle declines in cognition emerge) may enhance performance on a prefrontal cortex-mediated task sensitive to aging. “We hypothesized that augmenting SR expression within mPFC glutamatergic neurons would improve attention and cognitive flexibility in middle-aged rats and facilitate synaptic responses in the mPFC. Thus, for this study, SR expression was upregulated in pyramidal neurons of the mPFC through lenti-viral technology to enhance NMDAR function and evaluate its impact on cognitive flexibility and NMDAR-mediated synaptic transmission in middle-age rats.” Middle-aged (~12 mo) male Fischer-344 rats were injected bilaterally in the medial prefrontal cortex (mPFC) with viral vector (LV), SR (LV-SR) or control (LV-GFP). Rats were trained on the operant attentional set-shift task (AST) to examine cognitive flexibility and attentional function. LV-SR rats exhibited a faster rate of learning compared to controls during visual discrimination of the AST. Extradimensional set shifting and reversal were not impacted. Immunohistochemical analyses demonstrated that LV-SR significantly increased SR expression in the mPFC. Electrophysiological characterization of synaptic transmission in the mPFC slices obtained from LV-GFP and LV-SR animals indicated a significant increase in isolated NMDAR-mediated synaptic responses in LV-SR slices. Thus, results of the current study demonstrated that prefrontal SR upregulation in middle age rats can improve learning of task contingencies for visual discrimination and increase glutamatergic synaptic transmission, including NMDAR activity. “The results from this study support the beneficial effects of the D-serine pathway involvement in NMDAR-mediated transmission and cognitive function, expanding the literature to emphasize its role in not only the hippocampus but also the PFC. Thus, targeting this pathway could pose a potential route in reversing age-related cognitive decline and should be considered for future research.” DOI: https://doi.org/10.18632/aging.204652 Corresponding Author: Ashok Kumar - kash@ufl.edu Keywords - aging, medial prefrontal cortex, serine racemase, D-serine, NMDA receptor, cognitive flexibility 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@IMPACTJOURNALS.COM

A new research paper was published on the cover of Aging (Aging-US) Volume 15, Issue 7, entitled, “p21 facilitates chronic lung inflammation via epithelial and endothelial cells.” Cellular senescence is a stable state of cell cycle arrest that regulates tissue integrity and protects the organism from tumorigenesis. However, the accumulation of senescent cells during aging contributes to age-related pathologies. One such pathology is chronic lung inflammation. p21 (CDKN1A) regulates cellular senescence via inhibition of cyclin-dependent kinases (CDKs). However, its role in chronic lung inflammation and functional impact on chronic lung disease, where senescent cells accumulate, is less understood. In this new study, researchers Naama Levi, Nurit Papismadov, Julia Majewska, Lior Roitman, Noa Wigoda, Raya Eilam, Michael Tsoory, Ron Rotkopf, Yossi Ovadya, Hagay Akiva, Ofer Regev, and Valery Krizhanovsky from the Weizmann Institute of Science aimed to elucidate the role of p21 in chronic lung inflammation. “[...] we subjected p21 knockout (p21-/-) mice to repetitive inhalations of lipopolysaccharide (LPS), an exposure that leads to chronic bronchitis and accumulation of senescent cells.” The researchers utilized a lipopolysaccharide (LPS) inhalation-induced chronic bronchitis procedure to study the effects of repetitive LPS exposure on p21 knockout (p21-/-) mice. Furthermore, the team aimed to examine the specific contribution of the epithelial, endothelial and immune compartments to chronic bronchitis pathology. They found that p21 knockout led to a reduced presence of senescent cells, alleviated the pathological manifestations of chronic lung inflammation, and improved the fitness of the mice. The expression profiling of the lung cells revealed that resident epithelial and endothelial cells, but not immune cells, play a significant role in mediating the p21-dependent inflammatory response following chronic LPS exposure. “Therefore, we suggest that p21-dependent elimination of senescent cells may limit the damage induced by the pro-inflammatory presence of senescent cells, but also promote tissue regeneration. Therefore, inhibition of p21 represents a promising strategy for limiting age-related inflammatory disorders in general and obstructive lung diseases in particular.” DOI: https://doi.org/10.18632/aging.204622 Corresponding Author: Valery Krizhanovsky - valery.krizhanovsky@weizmann.ac.il Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204622 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, chronic lung inflammation, p21 (CDKN1A) 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 6, entitled, “Selenium as a predictor of metabolic syndrome in middle age women.” Metabolic syndrome (MetS) is a widespread clinical entity that has become almost a global epidemic. Selenium plays an important role in metabolic homeostasis. It has been suggested that it may also affect the expression and activity of PPAR-γ—an important mediator in energy balance and cell differentiation. In this new study, researchers Daria Schneider-Matyka, Anna Maria Cybulska, Małgorzata Szkup, Bogumiła Pilarczyk, Mariusz Panczyk, Agnieszka Tomza-Marciniak, and Elżbieta Grochans from Pomeranian Medical University in Szczecin, West Pomeranian University of Technology and Medical University of Warsaw aimed to analyze the relationships between these variables in the context of the health of women, for whom the risk of MetS increases with age. “The aim of this study was to search for a relationship between selenium concentrations and MetS, and to assess the impact of PPAR-γ on the incidence of MetS with regard to the moderating role of selenium.” The study involved 390 women in middle age. The stages of study: a survey-based part; anthropometric measurements; analysis of biological material (blood) in terms of glycemia, triglyceride, HDL, and selenium levels, as well as genetic analysis of the PPAR-γ polymorphisms. The researchers found that selenium may moderate the effect of the G allele of the PPAR-γ gene on the occurrence of elevated waist circumference (OR=1.030, 95%CI 1.005-1.057, p=0.020); and the effect of the C (OR=1.077, 95%CI 1.009-1.149, p=0.026) and the G alleles (OR=1.052, 95%CI 1.025-1.080, p<0.000) on the odds of elevated blood pressure. Women in whom HDL levels were not significantly reduced, had higher selenium levels (p=0.007). This study lead the team to 4 distinct conclusions: 1-The effect of selenium on MetS and its components has not been demonstrated. 2-The effect of individual alleles of the PPAR-γ gene on MetS and its components was not demonstrated. 3-The concentration of selenium may affect waist circumference in carriers of the G allele, and arterial hypertension in carriers of the C and G alleles by affecting the expression of PPAR-γ. 4-Higher selenium concentrations increased the odds of higher HDL levels in the group of subjects meeting the MetS criteria. “Recently, optimizing selenium intake in the population to prevent diseases associated with selenium deficiency or excess has been an important issue in modern health care worldwide. Our study suggests the influence of selenium levels on some components of MetS, such as waist circumference, blood pressure and HDL concentration. Thus, serum selenium concentration could be considered as one of the factors affecting some components of MetS.” DOI: https://doi.org/10.18632/aging.204590 Corresponding Author: Daria Schneider-Matyka - daria.schneider-matyka@pum.edu.pl Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204590 Keywords - aging, selenium, metabolic syndrome, middle aged women 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 https://www.Aging-US.com​​ for more about Aging (Aging-US). 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 6, entitled, “Knockout of AMD-associated gene POLDIP2 reduces mitochondrial superoxide in human retinal pigment epithelial cells.” Genetic and epidemiologic studies have significantly advanced our understanding of the genetic factors contributing to age-related macular degeneration (AMD). In particular, recent expression quantitative trait loci (eQTL) studies have highlighted POLDIP2 as a significant gene that confers risk of developing AMD. However, the role of POLDIP2 in retinal cells such as retinal pigment epithelium (RPE) and how it contributes to AMD pathology are unknown. In this new study, researchers Tu Nguyen, Daniel Urrutia-Cabrera, Luozixian Wang, Jarmon G. Lees, Jiang-Hui Wang, Sandy S.C. Hung, Alex W. Hewitt, Thomas L. Edwards, Sam McLenachan, Fred K. Chen, Shiang Y. Lim, Chi D. Luu, Robyn Guymer, and Raymond C.B. Wong from Royal Victorian Eye and Ear Hospital, University of Melbourne, St Vincent’s Institute of Medical Research, University of Tasmania, and The University of Western Australia report the generation of a stable human RPE cell line ARPE-19 with POLDIP2 knockout using CRISPR/Cas, providing an in vitro model to investigate the functions of POLDIP2. “We conducted functional studies on the POLDIP2 knockout cell line and showed that it retained normal levels of cell proliferation, cell viability, phagocytosis and autophagy. Also, we performed RNA sequencing to profile the transcriptome of POLDIP2 knockout cells.” Their results highlighted significant changes in genes involved in immune response, complement activation, oxidative damage and vascular development. They showed that loss of POLDIP2 caused a reduction in mitochondrial superoxide levels, which is consistent with the upregulation of the mitochondrial superoxide dismutase SOD2. In conclusion, this study demonstrates a novel link between POLDIP2 and SOD2 in ARPE-19, which supports a potential role of POLDIP2 in regulating oxidative stress in AMD pathology. “In summary, we have generated a POLDIP2 knockout ARPE-19 cell line using CRISPR/Cas9 and studied the biological functions of POLDIP2. To our knowledge, this is the first functional study of POLDIP2 in retinal cells to understand its potential role in AMD.” DOI: https://doi.org/10.18632/aging.204522 Corresponding Author: Raymond C.B. Wong - wongcb@unimelb.edu.au Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204522 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, age-related macular degeneration, retina, CRISPR/Cas, mitochondria superoxide, POLDIP2 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 by Aging (Aging-US) in Volume 15, Issue 6: “RNA virus-mediated changes in organismal oxygen consumption rate in young and old Drosophila melanogaster males.” _________________________________________ RNA viruses are responsible for approximately 70% of emerging infectious diseases in humans, according to a 2020 report by the National Academy of Medicine. Examples of RNA viruses include: influenza, hepatitis C, HIV, measles, zika, ebola, poliovirus, rhinovirus, rabies, and SARS-CoV-2—the virus responsible for the COVID-19 pandemic. After infection with an RNA virus, significant changes can take place in the host’s metabolism. While it is clear that disease tolerance declines as humans age, it is not yet clear how aging affects virus-induced changes in metabolism. “Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood.” In a new study, researchers Eli Hagedorn, Dean Bunnell, Beate Henschel, Daniel L. Smith Jr., Stephanie Dickinson, Andrew W. Brown, Maria De Luca, Ashley N. Turner, and Stanislava Chtarbanova from the University of Alabama, Indiana University, University of Arkansas for Medical Sciences, Arkansas Children’s Research Institute, and Jacksonville State University examined how an RNA virus can affect the respiration rate in male fruit flies (Drosophila melanogaster), both young and old. On March 22, 2023, their research paper was published in Aging’s Volume 15, Issue 6, entitled, “RNA virus-mediated changes in organismal oxygen consumption rate in young and old Drosophila melanogaster males.” Full blog - https://aging-us.org/2023/04/rna-virus-fruit-fly-model-first-study-to-measure-single-fly-respiration/ DOI - https://doi.org/10.18632/aging.204593 Corresponding author - Stanislava Chtarbanova - schtarbanova@ua.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204593 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Drosophila melanogaster, virus infection, single-fly respirometry, metabolism 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

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