Aging-US

BUFFALO, NY- February 20, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 3, entitled, “Defining the progeria phenome.” Progeroid disorders are a heterogenous group of rare and complex hereditary syndromes presenting with pleiotropic phenotypes associated with normal aging. Due to the large variation in clinical presentation the diseases pose a diagnostic challenge for clinicians which consequently restricts medical research. In this new study, researchers Cecilie Worm, Maya Elena Ramirez Schambye, Garik V. Mkrtchyan, Alexander Veviorskiy, Anastasia Shneyderman, Ivan V. Ozerov, Alex Zhavoronkov, Daniela Bakula, and Morten Scheibye-Knudsen from the University of Copenhagen and Insilico Medicine aimed to accommodate this challenge by compiling a list of known progeroid syndromes and calculating the mean prevalence of their associated phenotypes, defining what they term the ‘progeria phenome’. “In this study, we have utilized phenome explorations to define the phenotypes associated with progerias and to develop tools to diagnose patients and identify new progeroid syndromes.” The data were used to train a support vector machine that is available at https://www.mitodb.com and able to classify progerias based on phenotypes. Furthermore, this allowed the researchers to investigate the correlation of progeroid syndromes and syndromes with various pathogenesis using hierarchical clustering algorithms and disease networks. They detected that ataxia-telangiectasia like disorder 2, spastic paraplegia 49 and Meier-Gorlin syndrome display strong association to progeroid syndromes, thereby implying that the syndromes are previously unrecognized progerias. “In conclusion, our study has provided tools to evaluate the likelihood of a syndrome or patient being progeroid. This is a considerable step forward in our understanding of what constitutes a premature aging disorder and how to diagnose them.” DOI - https://doi.org/10.18632/aging.205537 Corresponding author - Morten Scheibye-Knudsen - mscheibye@sund.ku.dk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205537 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, progeria, premature aging, phenome, clinical phenotype 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: Facebook - https://www.facebook.com/AgingUS/ X - 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Crossref is a non-profit organization that logs and updates citations for scientific publications. Each month, Crossref identifies a list of the most popular Aging (Aging-US) papers based on the number of times a DOI is successfully resolved. Below are Crossref’s Top 10 Aging DOIs in 2023. 10: Old-age-induced obesity reversed by a methionine-deficient diet or oral administration of recombinant methioninase-producing Escherichia coli in C57BL/6 mice DOI: https://doi.org/10.18632/aging.204783 Authors: Yutaro Kubota, Qinghong Han, Jose Reynoso, Yusuke Aoki, Noriyuki Masaki, Koya Obara, Kazuyuki Hamada, Michael Bouvet, Takuya Tsunoda, and Robert M. Hoffman 9: Metformin use history and genome-wide DNA methylation profile: potential molecular mechanism for aging and longevity DOI: https://doi.org/10.18632/aging.204498 Authors: Pedro S. Marra, Takehiko Yamanashi, Kaitlyn J. Crutchley, Nadia E. Wahba, Zoe-Ella M. Anderson, Manisha Modukuri, Gloria Chang, Tammy Tran, Masaaki Iwata, Hyunkeun Ryan Cho, and Gen Shinozaki 8: Age prediction from human blood plasma using proteomic and small RNA data: a comparative analysis DOI: https://doi.org/10.18632/aging.204787 Authors: Jérôme Salignon, Omid R. Faridani, Tasso Miliotis, Georges E. Janssens, Ping Chen, Bader Zarrouki, Rickard Sandberg, Pia Davidsson, and Christian G. Riedel 7: Characterization of the HDAC/PI3K inhibitor CUDC-907 as a novel senolytic DOI: https://doi.org/10.18632/aging.204616 Authors: Fares Al-Mansour, Abdullah Alraddadi, Buwei He, Anes Saleh, Marta Poblocka, Wael Alzahrani, Shaun Cowley, and Salvador Macip 6: Potential reversal of biological age in women following an 8-week methylation-supportive diet and lifestyle program: a case series DOI: https://doi.org/10.18632/aging.204602 Authors: Kara N. Fitzgerald, Tish Campbell, Suzanne Makarem, and Romilly Hodges 5: Leukocyte telomere length, T cell composition and DNA methylation age DOI: https://doi.org/10.18632/aging.101293 Authors: Brian H. Chen, Cara L. Carty, Masayuki Kimura, Jeremy D. Kark, Wei Chen, Shengxu Li, Tao Zhang, Charles Kooperberg, Daniel Levy, Themistocles Assimes, Devin Absher, Steve Horvath, Alexander P. Reiner, and Abraham Aviv 4: DNA methylation GrimAge strongly predicts lifespan and healthspan DOI: https://doi.org/10.18632/aging.101684 Authors: Ake T. Lu, Austin Quach, James G. Wilson, Alex P. Reiner, Abraham Aviv, Kenneth Raj, Lifang Hou, Andrea A. Baccarelli, Yun Li, James D. Stewart, Eric A. Whitsel, Themistocles L. Assimes, Luigi Ferrucci, and Steve Horvath 3: Deep biomarkers of aging and longevity: from research to applications DOI: https://doi.org/10.18632/aging.102475 Authors: Alex Zhavoronkov, Ricky Li, Candice Ma, and Polina Mamoshina 2: An epigenetic biomarker of aging for lifespan and healthspan DOI: https://doi.org/10.18632/aging.101414 Authors: Morgan E. Levine, Ake T. Lu, Austin Quach, Brian H. Chen, Themistocles L. Assimes, Stefania Bandinelli, Lifang Hou, Andrea A. Baccarelli, James D. Stewart, Yun Li, Eric A. Whitsel, James G Wilson, Alex P Reiner, Abraham Aviv, Kurt Lohman, Yongmei Liu, Luigi Ferrucci, and Steve Horvath 1: Chemically induced reprogramming to reverse cellular aging DOI: https://doi.org/10.18632/aging.204896 Authors: Jae-Hyun Yang, Christopher A. Petty, Thomas Dixon-McDougall, Maria Vina Lopez, Alexander Tyshkovskiy, Sun Maybury-Lewis, Xiao Tian, Nabilah Ibrahim, Zhili Chen, Patrick T. Griffin, Matthew Arnold, Jien Li, Oswaldo A. Martinez, Alexander Behn, Ryan Rogers-Hammond, Suzanne Angeli, Vadim N. Gladyshev, and David A. Sinclair Aging is an open-access, traditional, peer-reviewed journal that has published high-impact papers in all fields of aging research since 2009. All papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com. For media inquiries, please contact media@impactjournals.com.

BUFFALO, NY- February 15, 2024 – A new #research paper was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 3, entitled, “GV1001 reduces neurodegeneration and prolongs lifespan in 3xTg-AD mouse model through anti-aging effects.” GV1001, which mimics the activity of human telomerase reverse transcriptase, protects neural cells from amyloid beta (Aβ) toxicity and other stressors through extra-telomeric function, as noted in our prior in vitro studies. As per a recent phase II clinical trial, it improves cognitive function in patients with moderate to severe dementia. However, the underlying protective mechanisms remain unclear. In this new study, researchers Hyun-Hee Park, Hyuk Sung Kwon, Kyu-Yong Lee, Ye Eun Kim, Jeong-Woo Son, Na-Young Choi, Myung-Hoon Han, Dong Woo Park, Sangjae Kim, and Seong-Ho Koh from Hanyang University Guri Hospital, Hanyang University Graduate School of Biomedical Science and Engineering and Teloid Inc. aimed to investigate the effects of GV1001 on neurodegeneration, senescence, and survival in triple transgenic Alzheimer’s disease (AD) (3xTg-AD) mice. “ [...] we hypothesised that GV1001 might have anti-aging effects and improve neurodegeneration and senescence in vivo as a possible mechanism for its beneficial effects on AD.” GV1001 (1 mg/kg) was subcutaneously injected into old 3xTg-AD mice thrice a week until the endpoint for sacrifice, and survival was analysed. Magnetic resonance imaging (MRI) and Prussian blue staining (PBS) were performed to evaluate entry of GV1001 entrance into the brain. Diverse molecular studies were performed to investigate the effect of GV1001 on neurodegeneration and cellular senescence in AD model mice, with a particular focus on BACE, amyloid beta1-42 (Aβ1-42), phosphorylated tau, volume of dentate gyrus, β-galactosidase positive cells, telomere length, telomerase activity, and ageing-associated proteins. GV1001 crossed the blood-brain barrier, as confirmed by assessing the status of ferrocenecarboxylic acid-conjugated GV1001 using magnetic resonance imaging and PBS. GV1001 increased the survival of 3xTg-AD mice. It decreased BACE and Aβ1-42 levels, neurodegeneration (i.e., reduced CA1, CA3 and dentate gyrus volume, decreased levels of senescence-associated β-galactosidase positive cells, and increased telomere length and telomerase activity), and levels of ageing-associated proteins. “We suggest that GV1001 exerts anti-ageing effects in 3xTg-AD mice by reducing neurodegeneration and senescence, which contributes to improved survival.” DOI - https://doi.org/10.18632/aging.205489 Corresponding authors - Sangjae Kim - chiron@gemvax.com, and Seong-Ho Koh - ksh213@hanyang.ac.kr 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: Facebook - https://www.facebook.com/AgingUS/ X - 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY- February 13, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 2, entitled, “IL-17 promotes IL-18 production via the MEK/ERK/miR-4492 axis in osteoarthritis synovial fibroblasts.” The concept of osteoarthritis (OA) as a low-grade inflammatory joint disorder has been widely accepted. Many inflammatory mediators are implicated in the pathogenesis of OA. Interleukin (IL)-18 is a pleiotropic cytokine with versatile cellular functions that are pathogenetically important in immune responses, as well as autoimmune, inflammatory, and infectious diseases. IL-17, a proinflammatory cytokine mainly secreted by Th17 cells, is upregulated in OA patients. However, the role of IL-17 in OA progression is unclear. In this new study, researchers Kun-Tsan Lee, Chih-Yang Lin, Shan-Chi Liu, Xiu-Yuan He, Chun-Hao Tsai, Chih-Yuan Ko, Yuan-Hsin Tsai, Chia-Chia Chao, Po-Chun Chen, and Chih-Hsin Tang from National Chung-Hsing University, Taichung Veterans General Hospital, Shin-Kong Wu Ho-Su Memorial Hospital, Mackay Medical College, China Medical University, Show-Chwan Memorial Hospital, Fu-Jen Catholic University, National Taiwan Normal University, Asia University, and China Medical University Hsinchu Hospital used synovial tissues collected from healthy donors and OA patients to detect the expression level of IL-18 by immunohistochemistry stain. “Elucidation of the molecular mechanisms and main factors involved in OA pathogenesis may help with the development of novel therapeutic targets that relieve OA pain or prevent the disease from progressing.” The OA synovial fibroblasts (OASFs) were incubated with recombinant IL-17 and subjected to Western blot, qPCR, and ELISA to examine IL-18 expression level. The chemical inhibitors and siRNAs which targeted signal pathways were used to investigate signal pathways involved in IL-17-induced IL-18 expression. The microRNAs which participated IL-18 expression were surveyed with online databases miRWalk and miRDB, followed by validation with qPCR. This study revealed significantly higher levels of IL-18 expression in synovial tissue from OA patients compared with healthy controls, as well as increased IL-18 expression in OASFs from rats with severe OA. In vitro findings indicated that IL-17 dose-dependently promoted IL-18 production in OASFs. Molecular investigations revealed that the MEK/ERK/miR-4492 axis stimulated IL-18 production when OASFs were treated with IL-17. “This study provides novel insights into the role of IL-17 in the pathogenesis of OA, which may help to inform OA treatment in the future.” DOI - https://doi.org/10.18632/aging.205462 Corresponding authors - Po-Chun Chen - pcchen@ntnu.edu.tw, and Chih-Hsin Tang - chtang@mail.cmu.edu.tw 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: Facebook - https://www.facebook.com/AgingUS/ X - 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY- February 7, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 2, entitled, “PROX1 interaction with α-SMA-rich cancer-associated fibroblasts facilitates colorectal cancer progression and correlates with poor clinical outcomes and therapeutic resistance.” The tumor microenvironment (TME) plays a vital role in tumor progression through intricate molecular interactions. Cancer-associated fibroblasts (CAFs), notably those expressing alpha-smooth muscle actin (α-SMA) or myofibroblasts, are instrumental in this context and correlate with unfavorable outcomes in colorectal cancer (CRC). While several transcription factors influence TME, the exact regulator causing CAF dysregulation in CRC remains elusive. Prospero Homeobox 1 (PROX1) stands out, as its inhibition reduces α-SMA-rich CAF activity. However, the therapeutic role of PROX1 is debated due to inconsistent study findings. In this new study, researchers Shiue-Wei Lai, Yi-Chiao Cheng, Kee-Thai Kiu, Min-Hsuan Yen, Ying-Wei Chen, Vijesh Kumar Yadav, Chi-Tai Yeh, Kuang-Tai Kuo, and Tung-Cheng Chang from Taipei’s National Defense Medical Center, Taipei Medical University, Taipei Medical University Shuang-Ho Hospital, and National Taitung University used the ULCAN portal and noted an elevated PROX1 level in advanced colon adenocarcinoma, linking to a poor prognosis. Their assays determined the impact of PROX1 overexpression on CRC cell properties, while co-culture experiments spotlighted the PROX1-CAF relationship. Molecular expressions were validated by qRT-PCR and Western blots, with in vivo studies further solidifying the observations. “Our study emphasized the connection between PROX1 and α-SMA in CAFs.” Elevated PROX1 in CRC samples correlated with increased α-SMA in tumors. PROX1 modulation influenced the behavior of specific CRC cells, with its overexpression fostering invasiveness. Kaplan-Meier evaluations demonstrated a link between PROX1 or α-SMA and survival outcomes. Consequently, PROX1, alone or with α-SMA, emerges as a CRC prognostic marker. Co-culture and animal experiments further highlighted this relationship. PROX1 appears crucial in modulating CRC behavior and therapeutic resistance within the TME by influencing CAFs, signifying the combined PROX1/α-SMA gene as a potential CRC prognostic marker. The concept of developing inhibitors targeting this gene set emerges as a prospective therapeutic strategy. However, this study is bound by limitations, including potential challenges in clinical translation, a focused exploration on PROX1/α-SMA potentially overlooking other significant molecular contributors, and the preliminary nature of the inhibitor development proposition. “As we advance in this field, the development and clinical validation of small-molecule inhibitors targeting PROX1/α-SMA become imperative, paving the way to refine and optimize CRC therapeutic interventions.” DOI - https://doi.org/10.18632/aging.205447 Corresponding author - Tung-Cheng Chang - 09432@s.tmu.edu.tw 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​​. MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY- February 6, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 2, entitled, “Epigenetic drift underlies epigenetic clock signals, but displays distinct responses to lifespan interventions, development, and cellular dedifferentiation.” Changes in DNA methylation with age are observed across the tree of life. The stereotypical nature of these changes can be modeled to produce epigenetic clocks capable of predicting chronological age with unprecedented accuracy. Despite the predictive ability of epigenetic clocks and their utility as biomarkers in clinical applications, the underlying processes that produce clock signals are not fully resolved, which limits their interpretability. In this new study, researchers Emily M. Bertucci-Richter, Ethan P. Shealy, and Benjamin B. Parrott from the University of Georgia developed a computational approach to spatially resolve the within read variability or “disorder” in DNA methylation patterns and test if age-associated changes in DNA methylation disorder underlie signals comprising epigenetic clocks. “Herein, we apply novel read-based strategies to resolve age-associated epigenetic disorder across the mouse genome.” The team found that epigenetic clock loci are enriched in regions that both accumulate and lose disorder with age, suggesting a link between DNA methylation disorder and epigenetic clocks. They then developed epigenetic clocks that are based on regional disorder of DNA methylation patterns and compare their performance to other epigenetic clocks by investigating the influences of development, lifespan interventions, and cellular dedifferentiation. The researchers identified common responses as well as critical differences between canonical epigenetic clocks and those based on regional disorder, demonstrating a fundamental decoupling of epigenetic aging processes. “Collectively, we identify key linkages between epigenetic disorder and epigenetic clocks and demonstrate the multifaceted nature of epigenetic aging in which stochastic processes occurring at non-random loci produce predictable outcomes.” DOI - https://doi.org/10.18632/aging.205503 Corresponding author - Emily M. Bertucci-Richter - embertucci@gmail.com Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205503 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, epigenetic aging, epigenetic drift, epigenetic rejuvenation, lifespan, DNA methylation 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: Facebook - https://www.facebook.com/AgingUS/ X - 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and heterogeneous form of cancer that affects thousands of individuals worldwide. The prognosis for HNSCC patients can vary greatly, depending on factors such as tumor stage and site. The tumor microenvironment (TME) plays a crucial role in tumorigenesis and disease progression, with cellular senescence being a key component. Senescent cells, characterized by cell-cycle arrest, have been shown to have both tumor-suppressive and tumor-promoting effects. However, the prognostic significance of senescence-related TME genes in HNSCC remains poorly understood. In a new study, researchers Young Chan Lee, Yonghyun Nam, Minjeong Kim, Su Il Kim, Jung-Woo Lee, Young-Gyu Eun, and Dokyoon Kim from Kyung Hee University, Kyung Hee University Hospital at Gangdong, and the University of Pennsylvania aimed to investigate the prognostic significance of senescence-related TME genes in HNSCC and their potential implications for immunotherapy response. They utilized data from The Cancer Genome Atlas (TCGA) to identify two distinct subtypes of HNSCC based on the expression of senescence-related TME genes. The team then constructed a risk model consisting of senescence-related TME core genes (STCGs) and validated its prognostic capability in independent cohorts. Their research paper was chosen as an Aging cover paper and published in Volume 16, Issue 2, entitled, “Prognostic significance of senescence-related tumor microenvironment genes in head and neck squamous cell carcinoma.” Full blog - https://aging-us.org/2024/02/senescence-related-tme-genes-as-key-prognostic-predictors-in-hnscc/ Paper DOI - https://doi.org/10.18632/aging.205346 Corresponding authors - Young-Gyu Eun - ygeun@khu.ac.kr, and Dokyoon Kim - dokyoon.kim@pennmedicine.upenn.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205346 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, head and neck cancer, immunotherapy, microenvironment, single cell 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: Facebook - https://www.facebook.com/AgingUS/ X - 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY- January 31, 2024 – A new #research paper was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 2, entitled, “Prognostic significance of senescence-related tumor microenvironment genes in head and neck squamous cell carcinoma.” The impact of the senescence related microenvironment on cancer prognosis and therapeutic response remains poorly understood. In this new study, researchers Young Chan Lee, Yonghyun Nam, Minjeong Kim, Su Il Kim, Jung-Woo Lee, Young-Gyu Eun, and Dokyoon Kim from Kyung Hee University, Kyung Hee University Hospital at Gangdong, and the University of Pennsylvania investigated the prognostic significance of senescence related tumor microenvironment genes (PSTGs) and their potential implications for immunotherapy response. Using the Cancer Genome Atlas- head and neck squamous cell carcinoma (HNSC) data, the researchers identified two subtypes based on the expression of PSTGs, acquired from tumor-associated senescence genes, tumor microenvironment (TME)-related genes, and immune-related genes, using consensus clustering. Using the LASSO, they constructed a risk model consisting of senescence related TME core genes (STCGs). The two subtypes exhibited significant differences in prognosis, genetic alterations, methylation patterns, and enriched pathways, and immune infiltration. “Our risk model stratified patients into high-risk and low-risk groups and validated in independent cohorts.” The high-risk group showed poorer prognosis and immune inactivation, suggesting reduced responsiveness to immunotherapy. Additionally, the team observed a significant enrichment of STCGs in stromal cells using single-cell RNA transcriptome data. Their findings highlight the importance of the senescence related TME in HNSC prognosis and response to immunotherapy. “This study contributes to a deeper understanding of the complex interplay between senescence and the TME, with potential implications for precision medicine and personalized treatment approaches in HNSC.” DOI - https://doi.org/10.18632/aging.205346 Corresponding authors - Young-Gyu Eun - ygeun@khu.ac.kr, and Dokyoon Kim - dokyoon.kim@pennmedicine.upenn.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205346 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, head and neck cancer, immunotherapy, microenvironment, single cell 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: Facebook - https://www.facebook.com/AgingUS/ X - 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY- January 30, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 1, entitled, “XRCC1: a potential prognostic and immunological biomarker in LGG based on systematic pan-cancer analysis.” X-ray repair cross-complementation group 1 (XRCC1) is a pivotal contributor to base excision repair, and its dysregulation has been implicated in the oncogenicity of various human malignancies. However, a comprehensive pan-cancer analysis investigating the prognostic value, immunological functions, and epigenetic associations of XRCC1 remains lacking. In this new study, researchers Guobing Wang, Yunyue Li, Rui Pan, Xisheng Yin, Congchao Jia, Yuchen She, Luling Huang, Guanhu Yang, Hao Chi, and Gang Tian from Southwest Medical University, The Affiliated Hospital of Southwest Medical University, Yibin Hospital of T.C.M, Medical School of Nanchang University, Fourth Military Medical University, and Ohio University aimed to address this knowledge gap by conducting a systematic investigation employing bioinformatics techniques across 33 cancer types. “Our analysis encompassed XRCC1 expression levels, prognostic and diagnostic implications, epigenetic profiles, immune and molecular subtypes, Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), immune checkpoints, and immune infiltration, leveraging data from TCGA, GTEx, CELL, Human Protein Atlas, Ualcan, and cBioPortal databases.” Notably, XRCC1 displayed both positive and negative correlations with prognosis across different tumors. Epigenetic analysis revealed associations between XRCC1 expression and DNA methylation patterns in 10 cancer types, as well as enhanced phosphorylation. Furthermore, XRCC1 expression demonstrated associations with TMB and MSI in the majority of tumors. Interestingly, XRCC1 gene expression exhibited a negative correlation with immune cell infiltration levels, except for a positive correlation with M1 and M2 macrophages and monocytes in most cancers. Additionally, the researchers observed significant correlations between XRCC1 and immune checkpoint gene expression levels. Lastly, their findings implicated XRCC1 in DNA replication and repair processes, shedding light on the precise mechanisms underlying its oncogenic effects. “Overall, our study highlights the potential of XRCC1 as a prognostic and immunological pan-cancer biomarker, thereby offering a novel target for tumor immunotherapy." DOI - https://doi.org/10.18632/aging.205426 Corresponding authors - Guanhu Yang - guanhuyang@gmail.com, Hao Chi - Chihao7511@163.com, and Gang Tian - tiangang@swmu.edu.cn Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, X-ray repair cross-complementation group 1, pan-cancer, prognosis, immune infiltration, tumor microenvironment 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/ X - 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY- January 24, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 1, entitled, “Targeting of FSP1 regulates iron homeostasis in drug-tolerant persister head and neck cancer cells via lipid-metabolism-driven ferroptosis.” Research has demonstrated that some tumor cells can transform into drug-tolerant persisters (DTPs), which serve as a reservoir for the recurrence of the disease. In this new study, researchers Yang-Che Wu, Chin-Sheng Huang, Ming-Shou Hsieh, Chih-Ming Huang, Syahru Agung Setiawan, Chi-Tai Yeh, Kuang-Tai Kuo, and Shao-Cheng Liu from Taipei Medical University-Shuang Ho Hospital, Taipei Medical University, Taitung Mackay Memorial Hospital, Tajen University, National Taitung University, and Taipei City’s National Defense Medical Center investigated lipid-metabolism-driven ferroptosis and its role in drug resistance and DTP generation in head and neck squamous cell carcinoma (HNSCC). “The regulatory roles of ferroptosis suppressor protein 1 (FSP1) in HNSCC metabolic regulation were investigated.” High levels of FSP1 were discovered in the tissues of patients who experienced relapse after cisplatin treatment. RNA sequencing indicated that a series of genes related to lipid metabolism were also highly expressed in tissues from these patients. Consistent results were obtained in primary DTP cells isolated from patients who experienced relapse. The Cancer Genome Atlas database confirmed this finding. This revealed that the activation of drug resistance in cancer cells is influenced by FSP1, intracellular iron homeostasis, and lipid metabolism. Next, the team generated human oral squamous cell carcinoma DTP cells (HNSCC cell line) to cisplatin and observed higher expression of FSP1 and lipid-metabolism-related targets in vitro. The shFSP1 blockade attenuated HNSCC-DTP cell stemness and downregulated tumor invasion and the metastatic rate. They found that cisplatin induced FSP1/ACSL4 axis expression in HNSC-DTPC cells. Finally, the researchers evaluated the HNSCC CSC-inhibitory functions of iFSP1 (a metabolic drug and ferroptosis inducer) used for neo-adjuvant chemotherapy; this was achieved by inducing ferroptosis in a patient-derived xenograft mouse model. “The present findings elucidate the link between iron homeostasis, ferroptosis, and cancer metabolism in HNSCC-DTP generation and acquisition of chemoresistance. The findings may serve as a suitable model for cancer treatment testing and prediction of precision treatment outcomes. In conclusion, this study provides clinically oriented platforms for evaluating metabolism-modulating drugs (FSP1 inhibitors) and new drug candidates of drug resistance and ferroptotic biomarkers.” Corresponding authors - Ming-Shou Hsieh - 22057@s.tmu.edu.tw, and Shao-Cheng Liu - m871435@mail.ndmctsgh.edu.tw 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: Facebook - https://www.facebook.com/AgingUS/ X - 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/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM