Aging-US

A new research paper was published in Aging (listed as “Aging (Albany NY)” by MEDLINE/PubMed and “Aging-US” by Web of Science) Volume 14, Issue 21, entitled, “The deubiquitylase USP7 is a novel cyclin F-interacting protein and regulates cyclin F protein stability.” Orderly progression through the cell cycle is driven by the periodic oscillations in the activity of cyclin-dependent kinases (CDKs). Cyclin F, unlike canonical and transcriptional cyclins, does not bind or activate any cyclin-dependent kinases. Instead, it harbors an F-box motif and primarily functions as the substrate recognition subunit of the Skp1-Cul1-F-box E3 ubiquitin ligase complex, SCFCyclin F. By targeting specific proteins for ubiquitin-mediated proteasomal degradation, cyclin F plays a critical role in the regulation of centrosomal duplication, DNA replication and repair, and maintenance of genomic stability. Cyclin F abundance and activity are tightly regulated throughout the cell cycle. However, the molecular mechanisms regulating cyclin F are scantily understood. In this new study, researchers Savitha S. Sharma, W. Jack Pledger and Paturu Kondaiah from Indian Institute of Science, Sri Shankara Cancer Hospital and Research Centre and University of Utah Health’s Huntsman Cancer Institute identified the deubiquitylase USP7 as a novel cyclin F-interacting protein. “In this study, we identify USP7 as a novel cyclin F-interacting protein and uncover novel aspects of cyclin F regulation mediated by this interaction.” The team observed that USP7 stabilizes cyclin F protein and that this function is independent of the deubiquitylase activity of USP7. Additionally, their data suggest that USP7 is also involved in the regulation of cyclin F mRNA. Pharmacological inhibition of the deubiquitylase activity of USP7 resulted in downregulation of cyclin F mRNA. “In conclusion, in this study, we demonstrate a new interacting partner of cyclin F, namely USP7, and the role of USP7 in the regulation of cyclin F mRNA and protein. This study highlights a potential role for the cyclin F-USP7 axis in pathological conditions, including cancer and neurodegenerative diseases.” DOI: https://doi.org/10.18632/aging.204372 Corresponding Author: Savitha S. Sharma - savitha.sharma@ssnccpr.org Video: https://www.youtube.com/watch?v=NMGevJWU9Ac Keywords: cyclin F, atypical cyclins, USP7, cell cycle, genomic integrity About Aging-US: Launched in 2009, Aging (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 go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com​​ and connect with us: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com

Listen to a blog summary of a trending research paper published by Aging (Aging-US), entitled, "ESR1 dysfunction triggers neuroinflammation as a critical upstream causative factor of the Alzheimer’s disease process.” _________________________________________________ The United States government currently has a mind-blowing annual budget of $3.5 billion designated for Alzheimer’s disease (AD) and dementia research funding. Therapeutics pushed forward thus far have been largely based on the amyloid-beta (Aβ) cascade hypothesis of AD. Surprisingly, despite decades and billions, these interventions have yielded little to no benefits for AD patients. This lack of efficacy has encouraged some researchers to rethink AD pathology and focus on discovering key triggers and mechanisms of neuroinflammation. “There has been a lengthy and ongoing scientific debate around the causative factors of AD, and the relative importance of both senile Aβ plaques and tau tangles has been largely informed by postmortem investigations of the AD brain. For several decades, the amyloid hypothesis has dominated the field, which has brought forth many high-profile therapeutic attempts that have produced side effects but no real benefits [5].” Women compose two-thirds of the United States Alzheimer’s population. Is this gender-specific risk a result of living longer or is it due to other causes, perhaps related to hormonal differences or gender-associated differential gene expression? Previous studies have found that estrogen may protect neurons from the damaging effects of amyloid-beta plaques and tau tangles. However, in women, estrogen levels tend to decline with age, which could be one reason why aging women are more susceptible to AD. In a new study, researchers Junying Liu, Shouli Yuan, Xinhui Niu, Robbie Kelleher, and Helen Sheridan from Trinity College Dublin, Peking University and Jilin University examined the potential relationship between the estrogen receptor-α gene (ESR1) and neuroinflammation. Their research paper was published on November 1, 2022, in Aging’s Volume 14, Issue 21, and entitled, “ESR1 dysfunction triggers neuroinflammation as a critical upstream causative factor of the Alzheimer’s disease process.” “AD is characterized by three major questions: Why is age the primary risk factor? Why are women more sensitive to the onset of this form of dementia? And why are neurons in areas of the brain that are essential for memory selectively targeted?” Full blog - https://aging-us.org/2022/11/is-estrogen-dysregulation-behind-alzheimers-pathology/ DOI - https://doi.org/10.18632/aging.204359 Corresponding authors - Junying Liu - juliu@tcd.ie Video - https://www.youtube.com/watch?v=NPWv39SJOpQ Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204359 Keywords - ESR1, Alzheimer’s disease, CEBPB/ATF4, APOE, pyroptosis 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/agingus​ 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 as "Aging (Albany NY)" by Medline/PubMed and "Aging-US" by Web of Science) Volume 14, Issue 21, entitled, “IGF1 gene therapy in middle-aged female rats delays reproductive senescence through its effects on hypothalamic GnRH and kisspeptin neurons.” The process of aging is the result of progressive loss of homeostasis and functional body impairment, including the central nervous system, where the hypothalamus plays a key role in regulating aging mechanisms. The consequences of aging include a chronic proinflammatory environment in the hypothalamus that leads to decreased secretion of gonadotropin-releasing hormone (GnRH) and impairs kisspeptin neuron functionality. In this new study, researchers Franco Juan Cruz Dolcetti, Eugenia Falomir-Lockhart, Francisco Acuña, Macarena Lorena Herrera, Sofia Cervellini, Claudio Gustavo Barbeito, Daniela Grassi, Maria-Angeles Arevalo, and María José Bellini from Consejo Nacional de Investigaciones Científicas y Técnicas (UNC-CONICET), Universidad Nacional de La Plata, Autonomous University of Madrid, Instituto Cajal, and Instituto de Salud Carlos III investigated the effect of insulin-like growth factor 1 (IGF1) gene therapy on hypothalamic kisspeptin/GnRH neurons and on microglial cells, that mediate the inflammatory process related with the aging process. “The aim of the present study is to investigate the effect of IGF1 gene therapy on estrous cycle, kisspeptin and GnRH neurons, and microglial cells in middle-aged female rats.” The results show that IGF1 rats have higher kisspeptin expression in the anteroventral periventricular (AVPV) nucleus and higher immunoreactivity of GnRH in the arcuate nucleus and median eminence. In addition, IGF1-treated animals exhibit increased numbers of Iba1+ microglial cells and MHCII+/Iba1+ in the AVPV and arcuate nuclei. In conclusion, IGF1 gene therapy maintains kisspeptin production in the AVPV nucleus, induces GnRH release in the median eminence, and alters the number and reactivity of microglial cells in middle-aged female rats. The researchers suggest that IGF1 gene therapy may have a protective effect against reproductive decline. “Based on our findings, we propose IGF1 gene therapy to delay reproductive senescence as a potential strategy to optimize lifespan and combat age-related health problems in women.” DOI: https://doi.org/10.18632/aging.204360 Corresponding Authors: Maria-Angeles Arevalo - arevalo@cajal.csic.es, and María José Bellini - mariajosebellini@med.unlp.edu.ar Keywords: IGF1, gene therapy, reproductive senescence, GnRH, kisspeptin, microglia Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204360 About Aging-US: Launched in 2009, Aging (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 go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com​​ and connect with us: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com.

A new research paper was published in Aging (listed as “Aging (Albany NY)” by MEDLINE/PubMed and “Aging-US” by Web of Science) Volume 14, Issue 20, entitled, “Age-associated changes in microglia activation and Sirtuin-1- chromatin binding patterns.” The aging process is associated with changes in mechanisms maintaining physiology, influenced by genetics and lifestyle, and impacting late life quality and longevity. Brain health is critical in healthy aging. Sirtuin 1 (Sirt1), a histone deacetylase with silencing properties, is one of the molecular determinants experimentally linked to health and longevity. In this new study, researchers Liana V. Basova, Nikki Bortell, Bruno Conti, Howard S. Fox, Richard Milner, and Maria Cecilia Garibaldi Marcondes from San Diego Biomedical Research Institute, University of Nebraska Medical Center and Oncovalent Therapeutics compared brain pathogenesis and Sirt1-chromatin binding dynamics in brain pre-frontal cortex from 2 groups of elder rhesus macaques (rhesus monkeys), divided by age of necropsy: shorter-lived animals (18-20 years old (yo)), equivalent to 60-70 human yo; and longer-lived animals (23-29 yo), corresponding to 80-100 human yo and modeling successful aging. These were compared with young adult brains (4-7 yo). “Our findings indicated drastic differences in the microglia marker Iba1, along with factors influencing Sirt1 levels and activity, such as CD38 (an enzyme limiting NAD that controls Sirt1 activity) and mir142 (a microRNA targeting Sirt1 transcription) between the elder groups.” Iba1 was lower in shorter-lived animals than in the other groups, while CD38 was higher in both aging groups compared to young. mir142 and Sirt1 levels were inversely correlated in longer-lived brains (>23yo), but not in shorter-lived brains (18-20 yo). They also found that Sirt1 binding showed signs of better efficiency in longer-lived animals compared to shorter-lived ones, in genes associated with nuclear activity and senescence. “Overall, differences in neuroinflammation and Sirt1 interactions with chromatin distinguished shorter- and longer-lived animals, suggesting the importance of preserving microglia and Sirt1 functional efficiency for longevity.” DOI: https://doi.org/10.18632/aging.204329 Corresponding Author: Maria Cecilia Garibaldi Marcondes - cmarcondes@SDBRI.org Keywords: aging, brain, rhesus macaques, microglia, Sirtuin-1 Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204329 Video: https://www.youtube.com/watch?v=Cz33TWM4so4 About Aging-US: Launched in 2009, Aging (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 go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com​​ and connect with us: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com

Scientific integrity is a crucial component of scholarly publishing for any credible journal. Peer-reviewed, open-access journal Aging (listed as “Aging (Albany NY)” by Medline/PubMed and “Aging-US” by Web of Science) has recently presented its Scientific Integrity process. Launched in 2009, Aging is an open-access biomedical journal dedicated to publishing high-quality, aging-focused research. Aging publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Aging has a scientific integrity process to ensure that publications meet a number of scrupulous criteria for authenticity and integrity. Each published paper is thoroughly analyzed by diligent reviewers and services, including multiple in-house developed image forensics softwares. A growing industry of digital technologies, tools and ideas are constantly being added to Aging’s scientific integrity toolbox. Aging’s Scientific Integrity process is built upon six critical components: 1-Easily Accessible Ethics Statements 2-Devotion to Industry Standards for Scientific Publishing 3-Rigorous and Insightful Peer Review 4-Detection and Zero-Tolerance of Plagiarism 5-Leading-Edge Image Forensics 6-Post-Publication Investigations (if needed) The new webpage also depicts publishing statistics in a detailed graph —showcasing a visual representation of the number of post-publication corrections and retractions by Aging compared to the industry average, between 2010 and 2022. As of September 2022, Aging’s average rate of corrections/retractions since 2009 is a low 2.33%. The industry average correction/retraction rate is 3.80%. Aging’s highly-effective scientific integrity process allows researchers to read, share and cite Aging papers with confidence. Learn more about Aging’s Scientific Integrity Process: https://www.aging-us.com/scientific-integrity Video: https://www.youtube.com/watch?v=5wbStfARUlI Please visit our website at www.Aging-US.com​​ and connect with us socially: 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/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com

A new research perspective was published in Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) Volume 14, Issue 20, entitled, “Rapamycin treatment early in life reprograms aging: hyperfunction theory and clinical practice.” On October 24, 2022, Mikhail Blagosklonny, M.D., Ph.D. from Roswell Park Comprehensive Cancer Center published a riveting research perspective discussing the clinical application of early-life rapamycin treatment and its ability to reprogram aging, based on the hyperfunction theory. “Making provocative headlines, three outstanding publications demonstrated that early-life treatment with rapamycin, including treatments during developmental growth, extends lifespan in animals, confirming predictions of hyperfunction theory, which views aging as a quasi-program (an unintended continuation of developmental growth) driven in part by mTOR. Despite their high theoretical importance, clinical applications of two of these studies in mice, Drosophila and Daphnia cannot be implemented in humans because that would require growth retardation started at birth. A third study demonstrated that a transient (around 20% of total lifespan in Drosophila) treatment with rapamycin early in Drosophila adult life is as effective as lifelong treatment, whereas a late-life treatment is not effective. However, previous studies in mice demonstrated that a transient late-life treatment is highly effective. Based on hyperfunction theory, this article attempts to reconcile conflicting results and suggests the optimal treatment strategy to extend human lifespan.” DOI: https://doi.org/10.18632/aging.204354 Corresponding Author: Mikhail V. Blagosklonny - Corresponding Email: Blagosklonny@oncotarget.com Video - https://www.youtube.com/watch?v=Br7iD48fKF4 Keywords: senescence, gerostatics, geroscience, sirolimus, healthspan Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204354 About Aging-US: Launched in 2009, Aging (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 go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com​​ and connect with us: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com Aging (Aging-US) Journal Office 6666 E. Quaker Str., Suite 1B Orchard Park, NY 14127 Phone: 1-800-922-0957, option 1

Dr. Ya-Jen Chiu from the Department of Life Science at National Taiwan Normal University in Taipei, discusses a research paper she co-authored that was published by Aging (Aging-US) in Volume 14, Issue 18, entitled, “Novel TRKB agonists activate TRKB and downstream ERK and AKT signaling to protect Aβ-GFP SH-SY5Y cells against Aβ toxicity.” DOI - https://doi.org/10.18632/aging.204306 Corresponding authors - Chiung-Mei Chen - cmchen@cgmh.org.tw, Ying-Chieh Sun - sun@ntnu.edu.tw, Guey-Jen Lee-Chen - t43019@ntnu.edu.tw Video - https://www.youtube.com/watch?v=1rT96K9VeZw Transcript - https://aging-us.net/2022/11/01/behind-the-study-novel-trkb-agonists-activate-trkb-and-downstream-erk-and-akt-signaling/ Abstract Decreased BDNF and impaired TRKB signaling contribute to neurodegeneration in Alzheimer's disease (AD). We have shown previously that coumarin derivative LM-031 enhanced CREB/BDNF/BCL2 pathway. In this study we explored if LM-031 analogs LMDS-1 to -4 may act as TRKB agonists to protect SH-SY5Y cells against Aβ toxicity. By docking computation for binding with TRKB using 7,8-DHF as a control, all four LMDS compounds displayed potential of binding to domain d5 of TRKB. In addition, all four LMDS compounds exhibited anti-aggregation and neuroprotective efficacy on SH-SY5Y cells with induced Aβ-GFP expression. Knock-down of TRKB significantly attenuated TRKB downstream signaling and the neurite outgrowth-promoting effects of these LMDS compounds. Among them, LMDS-1 and -2 were further examined for TRKB signaling. Treatment of ERK inhibitor U0126 or PI3K inhibitor wortmannin decreased p-CREB, BDNF and BCL2 in Aβ-GFP cells, implicating the neuroprotective effects are via activating TRKB downstream ERK, PI3K-AKT and CREB signaling. LMDS-1 and -2 are blood-brain barrier permeable as shown by parallel artificial membrane permeability assay. Our results demonstrate how LMDS-1 and -2 are likely to work as TRKB agonists to exert neuroprotection in Aβ cells, which may shed light on the potential application in therapeutics of AD. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204306 Keywords - aging, Alzheimer’s disease, TRKB agonists, Aβ, neuroprotection, therapeutics 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/agingus​ 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 as "Aging (Albany NY)" by Medline/PubMed and "Aging-US" by Web of Science) Volume 14, Issue 20, entitled, “Downregulation of senescence-associated secretory phenotype by knockdown of secreted frizzled-related protein 4 contributes to the prevention of skin aging.” There is growing evidence that the appearance and texture of the skin that is altered during the aging process are considerably enhanced by the accumulation of senescent dermal fibroblasts. These senescent cells magnify aging via an inflammatory, histolytic, and senescence-associated secretory phenotype (SASP). Secreted frizzled-related protein 4 (SFRP4) was previously determined to be expressed in dermal fibroblasts of aging skin, and its increased expression has been shown to promote cellular senescence. However, its role in the SASP remains unknown. In this new study, researchers Kento Takaya, Toru Asou and Kazuo Kishi from Keio University School of Medicine’s Department of Plastic and Reconstructive Surgery investigated the classical model of skin fibroblasts based on Hayflick’s mitotic limit, the observation of SFRP4 expression in replicating senescent cells, and the effect of regulating this on the suppression of SASP and aging skin. “These results may contribute to the development of new therapies to ameliorate skin aging.” The researchers found that SFRP4 was significantly expressed in p16ink4a-positive human skin fibroblasts and that treatment with recombinant SFRP4 promoted SASP and senescence, whereas siRNA knockdown of SFRP4 suppressed SASP. They also found that knockdown of SFRP4 in mouse skin ameliorates age-related reduction of subcutaneous adipose tissue, panniculus carnosus muscle layer, and thinning and dispersion of collagen fibers. These findings suggest a potential candidate for the development of new skin rejuvenation therapies that suppress SASP. “This study shows that SFRP4, which is specifically expressed in aged p16ink4a-positive skin fibroblasts, contributes to SASP, and that treatment with SFRP4 causes worsening of this phenotype. To the best of our knowledge, the present study is the first to report that the suppression of SFRP4 expression in vivo ameliorates skin aging-related phenotypes, that is, adipose tissue atrophy and collagen fiber thinning, via SASP suppression.” DOI: https://doi.org/10.18632/aging.204273 Corresponding Author: Kento Takaya - Email: kento-takaya312@keio.jp Keywords: skin, fibroblast, SASP, SFRP4 Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204273 About Aging-US: Launched in 2009, Aging (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 go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com​​ and connect with us: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com. Aging (Aging-US) Journal Office 6666 E. Quaker Str., Suite 1B Orchard Park, NY 14127 Phone: 1-800-922-0957, option 1

Dr. Takushi Namba, Associate Professor at Kochi University in Japan, discusses a research paper he co-authored that was published by Aging (Aging-US) in Volume 14, Issue 19, entitled, “Lotus germ extract rejuvenates aging fibroblasts via restoration of disrupted proteostasis by the induction of autophagy.” DOI - https://doi.org/10.18632/aging.204303 Corresponding author - Takushi Namba - t-namba@kochi-u.ac.jp Video - https://www.youtube.com/watch?v=sXDw80HrqzM Abstract Cell aging attenuates cellular functions, resulting in time-dependent disruption of cellular homeostasis, which maintains the functions of proteins and organelles. Mitochondria are important organelles responsible for cellular energy production and various metabolic processes, and their dysfunction is strongly related to the progression of cellular aging. Here we demonstrate that disruption of proteostasis attenuates mitochondrial function before the induction of DNA damage signaling by proliferative and replicative cellular aging. We found that lotus (Nelumbo nucifera Gaertn.) germ extract clears abnormal proteins and agglutinates via autophagy-mediated restoration of mitochondrial function and cellular aging phenotypes. Pharmacological analyses revealed that DAPK1 expression was suppressed in aging cells, and lotus germ extract upregulated DAPK1 expression by stimulating the acetylation of histones and then induced autophagy by activating the DAPK1-Beclin1 signaling pathway. Furthermore, treatment of aging fibroblasts with lotus germ extract stimulated collagen production and increased contractile ability in three-dimensional cell culture. Thus, time-dependent accumulation of abnormal proteins and agglutinates suppressed mitochondrial function in cells in the early stage of aging, and reactivation of mitochondrial function by restoring proteostasis rejuvenated aging cells. Lotus germ extract rejuvenates aging fibroblasts via the DAPK1-Beclin1 pathway-induced autophagy to clear abnormal proteins and agglutinates. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204303 Keywords - aging, mitochondria, autophagy, proteostasis 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/agingus​ LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new review paper was published in Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) Volume 14, Issue 19, entitled, “RNA modifications in aging-associated cardiovascular diseases.” Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide that bears an enormous healthcare burden. Aging is a major contributing factor to CVDs. Functional gene expression network during aging is regulated by mRNAs transcriptionally and by non-coding RNAs epi-transcriptionally. RNA modifications alter the stability and function of both mRNAs and non-coding RNAs and are involved in differentiation, development and diseases. In this new review paper, researchers Xinyu Yang, Priyanka Gokulnath, H. Immo Lehmann, Zhitao Hou, Sun Yang, Liangzhen You, Guoxia Zhang, Yanwei Xing, Ji Lei, Guoping Li, Shuwen Guo, and Hongcai Shang from Fangshan Hospital and Dongzhimen Hospital (affiliated with Beijing University of Chinese Medicine), Massachusetts General Hospital, Harvard Medical School, Heilongjiang University of Chinese Medicine, and Chinese Academy of Chinese Medical Sciences reviewed major chemical RNA modifications on mRNAs and non-coding RNAs, including N6-adenosine methylation, N1-adenosine methylation, 5-methylcytidine, pseudouridylation, 2′ -O-ribose-methylation, and N7-methylguanosine, in the aging process with an emphasis on cardiovascular aging. They also summarize the currently available methods to detect RNA modifications and the bioinformatic tools to study RNA modifications. “More importantly, we discussed the specific implication of the RNA modifications on mRNAs and non-coding RNAs in the pathogenesis of aging-associated CVDs, including atherosclerosis, hypertension, coronary heart diseases, congestive heart failure, atrial fibrillation, peripheral artery disease, venous insufficiency, and stroke.” DOI: https://doi.org/10.18632/aging.204311 Corresponding Authors: Guoping Li; Shuwen Guo; Hongcai Shang - Corresponding Emails: gli21@mgh.harvard.edu; guo1163@163.com; shanghongcai@bucm.edu.cn Keywords: RNA modifications, aging, aging-related cardiovascular diseases, epitranscriptome Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204311 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/agingus​ LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM