Aging-US

The immune system is a vast and intricate network. Seven percent of the entire human genome is composed of immune-specific genes. This complex system has important functional and maintenance roles that involve clearing out foreign pathogens and sweeping away dead or dysfunctional cells. As do most human systems, the immune system experiences degradation with age. This degradation in aging populations results in inadequate immune responses to invading pathogens, self-antigens, undesirable and malfunctioning cells, and even to vaccines. “Furthermore, the aged immune system elicits an inadequate response to vaccines, leaving the elderly susceptible to pathogens despite being vaccinated against them. This is especially poignant in the wake of an ongoing pandemic where the mortality rate is disproportionately high in the elderly.” Researchers from the University of Florida authored a well-written review article (with exceptionally vivid figures and illustrations) exploring a potential cause of the aging immune system. They believe therapies that could target this cause may stave off age-related diseases and improve our quality of life as we age. The paper was published by Aging (Aging-US) in 2021, and entitled, “Cellular senescence in lymphoid organs and immunosenescence.” Full blog - https://www.impactjournals.com/journals/blog/aging/%e2%80%8b%e2%80%8bimmunosenescence-and-the-aging-immune-system/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203405 DOI - https://doi.org/10.18632/aging.203405 Full text - https://www.aging-us.com/article/203405/text Correspondence to: Daohong Zhou email: zhoudaohong@cop.ufl.edu Keywords: cellular senescence, immunosenescence, immune senescence, senescence associated secretory phenotype (SASP), thymus 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 http://www.Aging-US.com​​ or connect with us on: Twitter - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ SoundCloud - https://soundcloud.com/aging-us​ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

At present (September 2021), the direct targets of COVID-19 have been evidently clear. COVID-19 is causing the greatest threat to those of advanced age and with comorbidities. Despite this fact, there may be additional information gleaned from the accumulating stacks of clinical COVID-19 cases being aggregated around the world. A closer look at this data in sum may help researchers learn new insights about this fast spreading and quickly mutating virus. Moreover, learning about COVID-19 and its patterns may help scientists formulate better treatments and more effective vaccines. Researchers—from Buckingham Browne and Nichols School, Brigham and Women’s Hospital, Harvard Medical School, and Biotein—conducted a new study in an effort to decipher clinical COVID-19 data from multiple countries. Their aim was to learn additional information about the impact of COVID-19 across all age distributions, including childhood. The team wrote a trending research paper that was published by Aging (Aging-US) in August 2021, and entitled, “COVID-19 mortality rate in children is U-shaped.” Of note, one of the four authors of this research paper is the first author (and prolific teenager) named Nina Khera. This young woman (merely 15 years old) is a student and longevity researcher that is interested in preventing age-related diseases, including those related to brain aging and COVID-19. Khera is also the co-founder of a Canadian biotech company called Biotein. Full blog - https://www.impactjournals.com/journals/blog/aging/trending-with-impact-data-shows-unique-covid-19-patterns-in-childhood/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203442 DOI - https://doi.org/10.18632/aging.203442 Full text - https://www.aging-us.com/article/203442/text Correspondence to: Vadim N. Gladyshev email: vgladyshev@rics.bwh.harvard.edu Keywords: mortality, COVID-19, SARS-CoV-2, pediatrics, aging 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 http://www.Aging-US.com​​ or connect with us on: Twitter - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ SoundCloud - https://soundcloud.com/aging-us​ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

In 2016, researchers—from the University of California, Buck Institute for Research on Aging, Pacific Medical Center, and Brainreader—followed up on the anecdotal results from the 10 patients in this study. They provided objective results from quantitative magnetic resonance imaging (MRI) and neuropsychological testing. The researchers authored another paper on results of the MEND protocol, which was published by Aging and entitled, “Reversal of cognitive decline in Alzheimer’s disease.” To date, this paper has generated an Altmetric Attention score of 263. “In each of these cases, obvious subjective improvement, noted by the patient, his/her significant other, and his/her co-workers, was accompanied by clear, quantitated, objective improvement.” The MEND protocol, also known as the Bredesen Protocol (named after the creator of the protocol, Dr. Dale Bredesen), consists of a multifaceted, tailored approach to treating each AD patient for their individual symptoms of cognitive decline—and not only a few symptoms. This strategy uses a combination of diet, lifestyle, and therapeutic interventions. Treatment is based on the hypothesis that AD occurs due to an imbalance in an extensive plasticity network in the brain. The authors note that the MEND protocol is an iterative process and designed to improve with continued patient visits. “The therapeutic system described in this report derives from basic studies of the role of APP signaling and proteolysis in plasticity, and the imbalance in this receptor proteolysis that reproducibly occurs in Alzheimer’s disease.” Upon clinical assessment and lab testing, patient physical and cognitive health was evaluated. Based on this assessment, patients were prescribed a lengthy personalized therapeutic system. Among other objectives, the MEND protocol recommends treating diabetes; improving sleep and digestive health; reducing stress, inflammation, and blood sugar; increasing physical exercise, intellectual stimulation, antioxidants, and vitamins; and optimizing hormone balance, synthesis of acetylcholine, nerve growth factors, and mitochondrial function. “In each of these cases, obvious subjective improvement, noted by the patient, his/her significant other, and his/her co-workers, was accompanied by clear, quantitated, objective improvement.” Full blog - https://www.impactjournals.com/journals/blog/aging/reversing-alzheimers-disease-symptoms/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.100981 DOI - https://doi.org/10.18632/aging.100981 Full text - https://www.aging-us.com/article/100981/text Correspondence to: Dale E. Bredesen, MD email: dbredesen@buckinstitute.org Keywords: neurodegeneration, cognition, biomarkers, dementia, neuropsychology, imaging, Alzheimer's disease, Apolipoprotein E 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 http://www.Aging-US.com​​ or connect with us on: Twitter - https://twitter.com/AgingJrnl​ Facebook - https://www.facebook.com/AgingUS/​ SoundCloud - https://soundcloud.com/aging-us​ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Aging-US published "Beneficial effects of dietary supplementation with green tea catechins and cocoa flavanols on aging-related regressive changes in the mouse neuromuscular system" which reported that green tea extract (GTE) and cocoa-supplemented diets significantly improved survival rate of mice. GTE increased density of VAChT and VGluT2 afferent synapses on neuromuscular junctions. Cocoa, but not GTE, reduced aging-associated microgliosis and increased the proportion of neuroprotective microglial phenotypes. Dr. Jordi Calderó from IRBLleida said, "Sarcopenia, the progressive loss of skeletal muscle mass and function with age, is considered the main causative factor of the physical performance decline in the elderly." Sarcopenia, the progressive loss of skeletal muscle mass and function with age, is considered the main causative factor of the physical performance decline in the elderly. The compromised muscular function associated to sarcopenia has a negative impact on the life quality of older adults and increases the risk for disability, fall-associated injuries, morbidity, and mortality. The authors have recently reported a marked increase in the microglial and astroglial pro-inflammatory phenotypes (M1 and A1, respectively) in the spinal cord of aged mice. This may be due to the presence of anti-inflammatory and neuroprotective (M2 and A2) glial subpopulations. Caloric restriction, based on a diet low in calories, has been shown to attenuate aging sarcopenia in various species by acting at different levels of the skeletal muscle. Caloric restriction has also been reported to ameliorate age-related changes in rodent NMJs and to prevent MN and motor axon degeneration found to occur with aging [11, 21]. In a similar way, some dietary supplements have been shown to counteract age related changes that contribute to neuromuscular dysfunction (reviewed by [12) Plant flavonoids have gained particular attention as dietary compounds for keeping good health and preventing a number of diseases, particularly cardiac disorders and cancer. The Calderó Research Team concluded in their Aging-US Research Output that, green tea and cocoa flavonoids from GTE and cocoa significantly increased survival rate of aged mice. Both diets preserved NMJ innervation and maturity, delayed the senescence process of the skeletal muscle, and enhanced its regenerative capacity. Future research is needed to investigate whether higher doses of flavonoid are needed and/or longer-term interventions can help restore proper motor function. DOI - https://doi.org/10.18632/aging.203336 Full Text - https://www.aging-us.com/article/203336/text Correspondence to: Jordi Calderó email: jordi.caldero@udl.cat Keywords: sarcopenia, green tea, neuromuscular system, neural stem cells, aging, cocoa About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM

Aging-US published "A model of the aged lung epithelium in idiopathic pulmonary fibrosis" which reported that Iiopathic pulmonary fibrosis (IPF) is an age-related disorder that carries a universally poor prognosis. By exposing mouse alveolar epithelial cells to repeated, low doses of bleomycin, instead of usual one-time exposures, the authors uncovered changes strikingly similar to those in the IPF lung epithelium. They propose that this simple yet powerful tool could help uncover new biological mechanisms and assist in developing new pharmacological tools to treat the disease. Dr. Ross Summer from The Jane and Leonard Korman Respiratory Institute as well as Dr. Freddy Romero from The Baylor College of Medicine said, "Idiopathic pulmonary fibrosis (IPF) represents one of the most aggressive and irreversible lung diseases, has an unknown etiology, and limited therapeutic options." IPF arises from low-grade insults to the alveolar epithelium, which exhaust stem cell capacity and activate pathways that result in progressive tissue remodeling. Age represents the most significant risk factor for the development of IPF. Senescent cells are believed to drive immune cell and fibroblast activation via their production of secretory proteins (SASP), such as IL-6, TNF-β and TGF-β. Emerging evidence indicates that experimentally-induced pulmonary fibrosis can be ameliorated by targeting senescent cells for destruction [15]. This suggests a role for senolytic therapies in the treatment of IPf. The Summer/Romero Research Team concluded in their Aging-US Research Output, "we describe a novel model of the IPF lung epithelium that displays many characteristics of the dysfunctional IPF alveolar epithelium. Given its low cost and ease of implementation, we believe our model is ideally suited for uncovering the molecular underpinnings driving mitochondrial dysfunction, cellular senescence and loss of proteostasis in IPF. Further, we believe our model is also ideally suited for high throughput testing of novel pharmacological compounds directed at the alveolar epithelium. This includes drugs aimed at eliminating dysfunction epithelial cells, such as senolytic medications and agents that aim to restore health to the IPF alveolar epithelium" DOI - https://doi.org/10.18632/aging.203291 Full Text - https://www.aging-us.com/article/203291/text Correspondence to: Ross Summer email: Ross.Summer@Jefferson.edu and Freddy Romero email: Freddy.RomeroVasquez@bcm.edu Keywords: aging, IPF, mitochondria, proteostasis, epithelial cells About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY-August 20, 2021 – Aging is indexed by Web of Science: Science Citation Index Expanded (abbreviated as Aging‑US). In June 2021, Web of Science (Clarivate Analytics) released their 2020 JCR Impact Factor. Aging is pleased to report that our 2020 impact factor is 5.682. This number has increased from last year’s 4.831. Without self-citation, Aging’s 2020 impact factor is 5.279. Aging is listed in the Web of Science: Science Citation Index Expanded in two categories: Cell Biology and Geriatrics & Gerontology. According to the Journal Citation Indicator (JCI), Aging is ranked in the Q1 quartile in both categories. Since 2009, Aging has published research papers in all fields of aging research including, but not limited to, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. This journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, and prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases. To learn more about Aging, publication standards, and past or current issues, visit www.aging-us.com. Follow Aging on social media: Twitter – https://twitter.com/AgingJrnl Facebook – https://www.facebook.com/AgingUS SoundCloud – https://soundcloud.com/aging-us YouTube – https://www.youtube.com/agingus LinkedIn – https://www.linkedin.com/company/aging About Impact Journals: Impact Journals is an open-access publisher of research journals in biomedical sciences. Our publications focus on topics surrounding cancer research and all fields of aging research. Our mission is to provide scientists with the opportunity to share their exceptional discoveries, offer services that enable rapid dissemination of results, and to present vital findings from the many fields of biomedical science. Impact Journals LLC 6666 E.Quaker St. Ste. 1 Orchard Park, NY 14127

Researchers from Virginia Commonwealth University, Translational Genomics Research Institute, and the Banner Alzheimer’s Institute took part in a research study experimenting with combinations of therapeutic agents which they believe may improve neurodegenerative disorders. In 2021, their paper was published in Aging’s Volume 13, Issue 13, and entitled, “Inhibition of heat shock proteins increases autophagosome formation, and reduces the expression of APP, Tau, SOD1 G93A and TDP-43.” “In this paper we examined using isogenic colon cancer cells [with] several existing drugs that function by increasing autophagy and degrading misfolded proteins.” “Aberrant expression of chaperone proteins is found in many human pathologies including cancer, in virology and in AD, ALS and HC.” In this study, researchers tested drugs that have been used preclinically and clinically in several anticancer studies. The drugs used were: AR12, an antiviral chaperone ATPase inhibitor; Neratinib, a tyrosine kinase inhibitor; a combination of AR12 and Neratinib; Fingolimod, an immunosuppressive sphingosine l-phosphate receptor modulator; MMF, monomethyl fumarate; and a combination of Fingolimod and MMF. The cells they tested these drug combinations on in vitro included Vero cells (African Green Monkey kidney cells), isogenic HCT116 colon cancer cells (genetically manipulated colon cancer cells), and GBM6 cells (glioblastoma cancer stem cells). They also used plasmids, antibodies, and siRNAs. Researchers acknowledged that the use of non-neuronal cells may be a limitation of this study. “Our present studies were performed in non-neuronal cells and as a caveat, it is possible that our data in HCT116 and Vero cells will not be reflective of the same processes in neuronal cells.” Despite this caveat, results from their research were promising. Some combinations of these drugs were capable of knocking down many disease specific proteins that form toxic aggregates inside cells and in extracellular environments via autophagy. Full blog - https://www.impactjournals.com/journals/blog/aging/trending-with-impact-new-drug-combinations-inhibit-stress-proteins/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203297 DOI - https://doi.org/10.18632/aging.203297 Full text - https://www.aging-us.com/article/203297/text Correspondence to: Paul Dent email: paul.dent@vcuhealth.org Keywords: Alzheimer's, chaperone, GRP78, autophagy, neratinib 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 http://www.Aging-US.com​​ or connect with us on: Twitter - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ SoundCloud - https://soundcloud.com/aging-us​ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Aging-US published "MiR-513b-5p represses autophagy during the malignant progression of hepatocellular carcinoma by targeting PIK3R3" which reported MiR-513b-5p repressed liver cancer cell proliferation, migration/invasion, and induced apoptosis in vitro. Crucially, miR-513b-5p attenuated tumor growth of liver cancer cells in vivo. In the mechanical investigation, the authors identified that PIK3R3 mRNA 3′UTR was targeted by miR-513b-5p and miR-513b-5p suppressed PIK3R3 expression. PIK3R3 overexpression partly reversed miR-513b-5p-mediated autophagy, proliferation, and apoptosis of liver cancer cells. Consequently, they concluded in their Aging-US Research Output that miR-513b-5p repressed autophagy during the malignant progression of HCC by targeting PIK3R3. MiR-513b-5p may be applied as a therapeutic target for HCC. Dr. Rongjun Nie from The Guangxi Medical University said, "Liver cancer is a prevalent malignancy and the principal reason for tumor mortality globally, in which hepatocellular carcinoma (HCC) depicts 70–85% of the entire liver carcinoma weight." As the previous studies, autophagy is a crucial process during liver cancer development and a potential therapeutic target for liver cancer therapy, but the mechanisms are poorly understood. PIK3R3 acts as an oncogene of various cancers, containing glioma, lung cancer, and gastric cancer. As several miRNAs are involved in the modulation of autophagy in HCC and based on the crucial role of miR-513b-5p in cancer development, the authors selected miR-513b-5p as an example to evaluate its function in autophagy during liver cancer progression. In the present study, they were interested in the miR-513b-5p function in the modulation of autophagy during liver cancer progression. They demonstrated that miR-513b-5p attenuated autophagy during the malignant progression of liver cancer by targeting PIK3R3. The Nie Research Team concluded in their study, "miR-513b-5p repressed autophagy during the malignant progression of HCC by targeting PIK3R3. MiR-513b-5p may be applied as a therapeutic target for HCC." Sign up for free Altmetric alerts about this article DOI - https://doi.org/10.18632/aging.203135 Full Text - https://www.aging-us.com/article/203135/text Correspondence to: Rongjun Nie email: nrj2001@163.com Keywords: hepatocellular carcinoma, autophagy, progression, miR-513b-5p, PIK3R3 About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways. To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM

Aging-US published "Identification of RNA binding protein interacting with circular RNA and hub candidate network for hepatocellular carcinoma" which reported that 17 DERBPs, which were commonly dysregulated in HCC from The Clinical Proteomic Tumor Analysis Consortium, The Cancer Genome Atlas and International Cancer Genome Consortium projects, were utilized to construct the RBP-circRNA network. Additionally, gene set enrichment analysis showed that dysregulated TARDBP might be involved in some pathways related to the HCC pathogenesis. Therefore, a hub RBP-circRNA network was generated based on TARDBP. RNA immunoprecipitation and RNA pull-down confirmed that hsa_circ_0004913 binds to TARDBP. These findings, published in Aging-US, indicated a certain RBP-circRNA regulatory network potentially involved in the pathogenesis of HCC, which provides novel insights into the mechanism of study and biomarker identification for HCC. Dr. Yuhan Chen from The Southern Medical University said, "Hepatocellular carcinoma (HCC) is most common types of primary liver cancer." Previous studies have demonstrated that circRNAs can act as sponges of RNA binding protein, in the meantime RBPs are also able to participate in back-splicing. Therefore, the interaction with RBPs can be also regarded as a crucial element to explore functions of circRNAs. However, there are very few studies related to the effects of RBP-circRNA interactions on HCC, which requires more exploration. In this study, the authors screened out the differently expressed circRNA in HCC cases from Gene Expression Omnibus database and predicted the RBPs binding to DEcircRNA. After evaluating the expression level of RBPs in HCC from The Clinical Proteomic Tumor Analysis Consortium, International Cancer Genome Consortium and The Cancer Genome Atlas projects, they utilized 17 common DERBPs to construct the RBP-circRNA regulatory network in HCC. These findings indicated that certain RBP-circRNA networks may be closely related to HCC, which provides ideas for the mechanism of study for HCC. The Chen Research Team concluded in their Aging-US Research Output, "we identified some DERBPs interacting with circRNAs and generated RBP-circRNA regulatory networks for HCC. Among the DERBPs, high TARDBP expression was corelated with high grade, advanced stage and low macrophage fraction of HCC. We also constructed the hub RBP-circRNA network based on TARDBP and confirmed that hsa_circ_0004913 could bind to TARDBP, which may provide new clues for HCC mechanism study. However, there are also some limitations in our study. First, we only used TCGA, ICGC and CPTAC projects for analysis and little data resulted in only one RBP with prognostic significance, which may lead to the loss of some potential functional RBPs. Second, we didn’t classify samples according to the etiology and these identified circRNAs and RBPs may not be representative in HCC with different etiologies. Moreover, the number of HCC cases with circRNA data included in this study is relatively small. Due to our current lack of HCC samples and no survival information of HCC with circRNA expression profiles in GEO, we could not verify the expression and assess the prognostic value of circRNAs for HCC. In summary, our results indicated that some RBP-circRNA networks take a potential part in the pathogenesis of HCC and provide a new perspective for further mechanism study and biomarker development of HCC." DOI - https://doi.org/10.18632/aging.203139 Full Text - https://www.aging-us.com/article/203139/text Correspondence to: Yuhan Chen email: cspnr1@126.com Keywords: hepatocellular carcinoma, autophagy, progression, miR-513b-5p, PIK3R3

Listen to a blog summary of this research paper published by Aging, entitled, "Cdkn1a transcript variant 2 is a marker of aging and cellular senescence." The phenomenon in which cells are still metabolically active but can no longer proliferate is known as cellular senescence. Cellular senescence is a normal mechanism in development and tissue homeostasis—and a hallmark of aging. “Most of my lab works on a process called cellular senescence, which is a cellular response to stresses and damage, many of which increase with age,” Dr. Judy Campisi, Professor at the Buck Institute for Research on Aging and Senior Scientist at the Lawrence Berkeley National Lab, said in a recent Aging interview. An international team of researchers from Dr. Campisi’s lab are in search of new biological markers of cellular senescence and aging. Understanding mechanisms of aging such as senescence is key for developing new, safe interventions that may extend human life—with compounding socioeconomic and cultural impacts. Researchers from this lab come from institutions including the Buck Institute, the University of California, Berkeley’s Lawrence Berkeley National Lab, Universidad de Córdoba, Universidad Mayor, Geroscience Center for Brain Health and Metabolism, and Unity Biotechnology. The team published a trending 2021 paper in Aging‘s Volume 13, Issue 10, entitled, “Cdkn1a transcript variant 2 is a marker of aging and cellular senescence.” “Our results are, to our knowledge, the first to study Ckdn1a transcript variants in the context of aging.” There are a number of mechanisms that drive cellular senescence. Previously, mRNA and protein coding gene Cdkn1a transcript variant 1 (p21var1) has been better-studied compared to Cdkn1a transcript variant 2 (p21var2). The authors of this paper explain that this is likely because the encoded protein is identical to that encoded by variant 1, and both variants are regulated by p53. However, neither variants have ever before been studied in the context of aging. In this study, the researchers explored the expression levels of both Cdkn1a transcript variants 1 and 2 in the context of cellular senescence using several tissues from aged mice and a cell culture model of mouse cells. “The stringent cell growth arrest associated with cellular senescence is determined, among other mechanisms, by activities of cyclin-dependent kinase inhibitor proteins p16Ink4a and p21Cip1/Waf1, encoded by the Cdkn2a and Cdkn1a loci, respectively [1].” Study results showed that both variants are induced during cellular senescence. They showed that p21var1 and p21var2 are equally sensitive to transcriptional upregulation after p53 stabilization. The in vitro models also found that p21var2 is preferentially induced with age. “In sum, p21var2 expression is consistently elevated with age, in contrast with an absence of age-related change in p21var1 levels.” The researchers conducted further tests in vivo to examine the expression pattern of p21var2 and their results suggested that the circadian regulation of p21Cip1/Waf1 is driven solely by expression of Cdkn1a transcript variant 1. The team also induced cellular senescence in vivo with doxorubicin and ABT-263 (navitoclax) and evaluated the variants’ expression. These results confirmed their in vitro findings that p21var2 is more prone to cellular senescence than p21var1, thus making it a better marker for assessing the presence of senescent cells in vivo. “We show that, although tissue-specific exceptions may arise, p21var2 but not p21var1 is a better candidate marker of aging and senescence in mice.” DOI - doi.org/10.18632/aging.203110 Full Text - www.aging-us.com/article/203110/text Correspondence to: Judith Campisi email: jcampisi@buckinstitute.org About Aging Please visit our website at www.Aging-US.com​​ Aging is published by Impact Journals, LLC please visit www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM