Aging-US

Aging (Aging-US) published a new editorial paper in Volume 15, Issue 4, entitled, “Cognitive aging and dementia prevention: the time for psychology?” Modifiable risk and protective factors (e.g. engaging in active lifestyles and avoiding alcohol or smoking amongst others) are seen as key agents for dementia prevention, and they also exert an important effect on cognitive trajectories of non-demented older adults. In this new editorial, researchers David Bartrés-Faz, Cristina Solé-Padullés and Natalie L. Marchant from the University of Barcelona discuss recent research that has begun to identify psychological processes that confer relative risk and protection. “For example, repetitive negative thinking (RNT), a cognitive process defined by selfrelevant, persistent thoughts that elaborate on negative themes, has been associated with greater burden of typical Alzheimer’s disease (AD) pathological brain markers and accelerated cognitive decline over time [3].” In contrast, self-reflection, as well as purpose in life and other components of psychological well being, may help to maintain cognition and boost cognitive resilience against neuropathological burden. The possibility of incorporating psychological elements as key players in affecting one of the most important public health issues of the century opens a window of great therapeutic opportunity, particularly because fundamental psychological processes are at the core of cognitive-behavioral interventions that may help reduce dementia risk. However, for this emergent area to develop and wield maximum benefit, major unanswered questions need to be addressed. In their editorial, the researchers highlight three main areas for future research. “In summary, we propose that with momentum gathering, now is the time for psychology to make important contributions to cognitive ageing and dementia prevention research.” Full Paper: DOI: https://doi.org/10.18632/aging.204562 Corresponding Author: David Bartrés-Faz - dbartres@ub.edu Keywords: cognitive aging, psychological factors, dementia, prevention Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204562 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Blog summary of a research paper published in Aging (Aging-US) Volume 15, Issue 4: "Aging and memory are altered by genetically manipulating lactate dehydrogenase in the neurons or glia of flies." __________________________________________________________ The brain is a complex organ responsible for many critical functions, including the formation and retrieval of our memories. As we age, the brain undergoes changes that can affect cognitive abilities, including our memory. Understanding the mechanisms that underlie these changes is critical for developing therapies for age-related cognitive decline. “Over the last two decades there has been growing recognition that lactate, the end product of glycolysis, serves many functions, including acting as a source of energy, a signaling molecule, and even as an epigenetic regulator.” Lactate is a molecule that is produced during the metabolism of glucose in the body. It is a byproduct of anaerobic metabolism, which occurs when there is insufficient oxygen supply to meet the energy demands of the body. Lactate can be used as an energy source by some cells, such as the heart and skeletal muscles, and it can also be transported to the liver where it can be converted back into glucose. Lactate dehydrogenase (LDH), on the other hand, is an enzyme that catalyzes the conversion of pyruvate to lactate (the reverse reaction of lactate production) and is also involved in other metabolic processes. This enzyme is found in many tissues of the body, including the heart, liver and skeletal muscles, and is released into the bloodstream when tissues are damaged. LDH is often used as a diagnostic marker for various medical conditions, such as heart attacks, liver disease and certain cancers. High levels of LDH in the blood may indicate tissue damage or cell death, while low levels may indicate a deficiency in the enzyme. Blog - https://aging-us.org/2023/03/fruit-flies-shed-new-light-on-memory-and-aging/ DOI - https://doi.org/10.18632/aging.204565 Corresponding authors - Ariel K. Frame - aframe@uwo.ca, and Robert C. Cumming - rcummin5@uwo.ca Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204565 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ MEDIA@IMPACTJOURNALS.COM

Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) published a new research paper in Volume 15, Issue 4, entitled, “Isoform-specific effects of neuronal repression of the AMPK catalytic subunit on cognitive function in aged mice.” AMP-activated protein kinase (AMPK) functions as a molecular sensor that plays a critical role in maintaining cellular energy homeostasis. Dysregulation of the AMPK signaling has been linked to synaptic failure and cognitive impairments. In a recent study, researchers Xueyan Zhou, Wenzhong Yang, Xin Wang, and Tao Ma from Wake Forest University School of Medicine demonstrated abnormally increased AMPK activity in the hippocampus of aged mice. The kinase catalytic subunit of AMPK exists in two isoforms α1 and α2, and their specific roles in aging-related cognitive deficits are unknown. “Taking advantage of the unique transgenic mice (AMPKα1/α2 cKO) recently developed by our group, we investigated how isoform-specific suppression of the neuronal AMPKα may contribute to the regulation of cognitive and synaptic function associated with aging.” The team found that aging-related impairment of long-term object recognition memory was improved with suppression of AMPKα1 but not AMPKα2 isoform. Moreover, aging-related spatial memory deficits were unaltered with suppression of either AMPKα isoform. Biochemical experiments showed that the phosphorylation levels of the eukaryotic initiation factor 2 α subunit (eIF2α) were specifically decreased in the hippocampus of the AMPKα1 cKO mice. They further performed large-scale unbiased proteomics analysis and revealed identities of proteins whose expression is differentially regulated with AMPKα isoform suppression. These novel findings may provide insights into the roles of AMPK signaling pathway in cognitive aging. “In summary, the current study reported that suppression of neuronal AMPKα1 isoform can improve aging-related impairments of long-term recognition memory.” Full Paper: DOI: https://doi.org/10.18632/aging.204554 Corresponding Author: Tao Ma - tma@wakehealth.edu Keywords: AMPK, aging, protein synthesis, learning and memory, proteomics Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204554 About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) published a new review paper in Volume 15, Issue 4, entitled, “Cellular senescence: when growth stimulation meets cell cycle arrest.” In this review, researcher Mikhail V. Blagosklonny, M.D., Ph.D., from Roswell Park Comprehensive Cancer Center discusses cellular senescence—a natural process that occurs as cells age and eventually stop dividing. Recent research has revealed that cellular senescence can also be triggered by hypertrophy and hyperfunctions. “At the very moment of cell-cycle arrest, the cell is not senescent yet. For several days in cell culture, the arrested cell is acquiring a senescent phenotype. What is happening during this geroconversion? Cellular enlargement (hypertrophy) and hyperfunctions (lysosomal and hyper-secretory) are hallmarks of geroconversion.” In his comprehensive review paper, Dr. Blagosklonny explores the complex relationship between growth stimulation and cell cycle arrest in cellular senescence. He discusses the various mechanisms that can lead to senescence, markers of senescence and geroconversion, and the importance of understanding these mechanisms and markers in the development of anti-aging drugs. “The same pathways that drive geroconversion are involved in organismal aging and age-related diseases. The same drugs that slow down geroconversion also extend lifespan, as tested in animals so far. Targets of gerostatics (e.g., mTOR, PI3K) are involved in aging of animals from worms to mammals. Therefore, gerostatics are anti-aging drugs. The model of geroconversion is useful to discover anti-aging drugs.” Dr. Blagosklonny is a renowned expert in the field of aging research. He has focused on the molecular mechanisms of aging, the hyperfunction theory of aging and the development of new drugs to combat age-related diseases. Dr. Blagosklonny’s research, perspectives and reviews have made significant contributions to our understanding of aging. Full Paper: DOI: https://doi.org/10.18632/aging.204543 Corresponding Author: Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.com Keywords: rapamycin, mTOR, hyperfunction theory of aging, cell volume and enlargement, gerogenic conversion Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204543

A new research paper was published on the cover of Aging (Aging-US) Volume 15, Issue 4, entitled, “Relationship between telomere shortening and early subjective depressive symptoms and cognitive complaints in older adults.” Telomere length (TL) has been reported to be associated with depression and cognitive impairment in elderly. Early detection of depression and cognitive impairment is important to delay disease progression. Therefore, in this new study, researchers Myung-Hoon Han, Eun-Hye Lee2, Hyun-Hee Park, Seong Hye Choi, and Seong-Ho Koh from Hanyang University and Inha University aimed to identify whether TL is associated with early subjective depressive symptoms and cognitive complaints among healthy elderly subjects. “Several hypotheses have been proposed to explain the emergence of a prematurely aged phenotype in late-life depression, such as glucocorticoid cascade dysregulation, increased allostatic load, and telomere shortening [10, 12].” This study was a multicenter, outcome assessor-blinded, 24-week, randomized controlled trial (RCT). Measurement of questionnaire and physical activity scores and blood sample analyses were performed at baseline and after six months of follow-up in all study participants. Linear regression analyses were performed to identify whether early subjective depressive symptoms, cognitive complaints, and several blood biomarkers are associated with TL. Altogether, 137 relatively healthy elderly individuals (60–79 years old) were enrolled in this prospective RCT. The team observed an approximate decrease of 0.06 and 0.11−0.14 kbps of TL per one point increase in the geriatric depression scale and cognitive complaint interview scores, respectively, at baseline and after six months of follow-up. They also found an approximate decrease of 0.08−0.09 kbps of TL per one point increase in interleukin (IL)-6 levels at baseline and after six months of follow-up. “In conclusion, we showed that both early subjective depressive symptoms and cognitive complaints in relatively healthy elderly individuals were associated with a relatively shorter TL in the randomized controlled prospective SUPERBRAIN study. In addition, a shorter TL was associated with increased IL-6 levels in our study participants. We believe that IL-6, an inflammatory cytokine, plays an important role in the relationship of shortening TL with early subjective depressive mood and cognitive complaints. Although the results will need to be verified through a large-scale RCT in the future, we believe that our findings will help prevent and treat depression and cognitive impairment in the healthy elderly.” DOI: https://doi.org/10.18632/aging.204533 Corresponding Authors: Seong Hye Choi - seonghye@inha.ac.kr, Seong-Ho Koh - ksh213@hanyang.ac.kr Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204533 Keywords - aging, telomere length, cognitive complaint, depressive symptom, interleukin-6 About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ MEDIA@IMPACTJOURNALS.COM

Listen to a blog summary of a trending research paper published in Volume 15, Issue 3 of Aging (Aging-US), entitled, "The lipidomes of C. elegans with mutations in asm-3/acid sphingomyelinase and hyl-2/ceramide synthase show distinct lipid profiles during aging." __________________________________________________ Lipids are a diverse group of biomolecules that are essential for life, including fats, oils, waxes, and steroids, and play crucial roles in cell membrane structure, energy storage and signaling. Lipidomics is the comprehensive analysis of lipids and their interactions in biological systems, with an aim to understand the role of lipids in cellular processes and their association with diseases. As we age, our cells undergo complex changes, including alterations in cellular lipid profiles. These changes are not only confined to humans; organisms such as the nematode Caenorhabditis elegans (C. elegans) are also subject to changes in lipid composition during aging. “For example, lipid classes including fatty acids (FA), triacylglycerols (TAG), sphingolipids (SL), and phospholipids (PL) have been identified as targets in lipid signatures related to aging [2, 3]. Furthermore, specific signatures are detected in the lipid profiles of those with age-related diseases, such as Alzheimer’s Disease [4–9]. In addition, the abundance of many fatty acid subtypes differs between the youth, elderly, and centenarians [10, 11].” In a recent study, researchers Trisha A. Staab, Grace McIntyre, Lu Wang, Joycelyn Radeny, Lisa Bettcher, Melissa Guillen, Margaret P. Peck, Azia P. Kalil, Samantha P. Bromley, Daniel Raftery, and Jason P. Chan from Marian University, the University of Washington and Juniata College investigate the lipid profiles of C. elegans with mutations in the genes asm-3/acid sphingomyelinase and hyl-2/ceramide synthase during aging. On February 13, 2023, their research paper was published in Aging’s Volume 15, Issue 3, entitled, “The lipidomes of C. elegans with mutations in asm-3/acid sphingomyelinase and hyl-2/ceramide synthase show distinct lipid profiles during aging.” Full blog - https://aging-us.org/2023/02/the-role-of-lipids-in-aging-insights-from-c-elegans/ DOI - https://doi.org/10.18632/aging.204515 Corresponding author - Jason P. Chan - jpchan@me.com Keywords - lipidomics, aging, sphingolipid metabolism, C. elegans, fatty acid metabolism About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) Volume 15, Issue 3, entitled, “Metformin use history and genome-wide DNA methylation profile: potential molecular mechanism for aging and longevity.” Metformin, a commonly prescribed anti-diabetic medication, has repeatedly been shown to hinder aging in pre-clinical models and to be associated with lower mortality for humans. It is, however, not well understood how metformin can potentially prolong lifespan from a biological standpoint. In this recent study, researchers 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 from Stanford University School of Medicine, University of Iowa, Tottori University Faculty of Medicine, University of Nebraska Medical Center College of Medicine, and Oregon Health and Science University School of Medicine hypothesized that metformin’s potential mechanism of action for longevity is through its epigenetic modifications. “To test our hypothesis, we conducted a post-hoc analysis of available genome-wide DNA methylation (DNAm) data obtained from whole blood collected from inpatients with and without a history of metformin use.” The researchers assessed the methylation profile of 171 patients (first run) and only among 63 diabetic patients (second run) and compared the DNAm rates between metformin users and nonusers. Enrichment analysis from the Kyoto Encyclopedia of Genes and Genome (KEGG) showed pathways relevant to metformin’s mechanism of action, such as longevity, AMPK and inflammatory pathways. They also identified several pathways related to delirium whose risk factor is aging. Moreover, top hits from the Gene Ontology (GO) included HIF-1α pathways. However, no individual CpG site showed genome-wide statistical significance (p < 5E-08). “This study may elucidate metformin’s potential role in longevity through epigenetic modifications and other possible mechanisms of action.” Read the Full Paper: DOI: https://doi.org/10.18632/aging.204498 Corresponding Author: Gen Shinozaki - gens@stanford.edu Keywords: metformin, longevity, diabetes, epigenetics, aging, inflammation, methylation Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204498 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

Crossref is a non-profit organization that logs and updates citations for scientific publications. Below are Crossref’s Top 10 Aging DOIs in 2022. 10: DNA- and telomere-damage does not limit lifespan: evidence from rapamycin DOI: https://doi.org/10.18632/aging.202674 Author: Mikhail V. Blagosklonny 9: Psychological factors substantially contribute to biological aging: evidence from the aging rate in Chinese older adults DOI: https://doi.org/10.18632/aging.204264 Authors: Fedor Galkin, Kirill Kochetov, Diana Koldasbayeva, Manuel Faria, Helene H. Fung, Amber X. Chen, and Alex Zhavoronkov 8: 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 7: Hallmarks of aging-based dual-purpose disease and age-associated targets predicted using PandaOmics AI-powered discovery engine DOI: https://doi.org/10.18632/aging.203960 Authors: Frank W. Pun, Geoffrey Ho Duen Leung, Hoi Wing Leung, Bonnie Hei Man Liu, Xi Long, Ivan V. Ozerov, Ju Wang, Feng Ren, Alexander Aliper, Evgeny Izumchenko, Alexey Moskalev, João Pedro de Magalhães, and Alex Zhavoronkov 6: CircRNA_100367 regulated the radiation sensitivity of esophageal squamous cell carcinomas through miR-217/Wnt3 pathway DOI: https://doi.org/10.18632/aging.102580 Authors: Junqi Liu, Nannan Xue, Yuexin Guo, Kerun Niu, Liang Gao, Song Zhang, Hao Gu, Xin Wang, Di Zhao, and Ruitai Fan 5: Five years of exercise intervention at different intensities and development of white matter hyperintensities in community dwelling older adults, a Generation 100 sub-study DOI: https://doi.org/10.18632/aging.203843 Authors: Anette Arild, Torgil Vangberg, Hanne Nikkels, Stian Lydersen, Ulrik Wisløff, Dorthe Stensvold, and Asta K. Håberg 4: The aging-related risk signature in colorectal cancer DOI: https://doi.org/10.18632/aging.202589 Authors: Taohua Yue, Shanwen Chen, Jing Zhu, Shihao Guo, Zhihao Huang, Pengyuan Wang, Shuai Zuo, and Yucun Liu 3: 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 2: Nrf2 inhibits ferroptosis and protects against acute lung injury due to intestinal ischemia reperfusion via regulating SLC7A11 and HO-1 DOI: https://doi.org/10.18632/aging.103378 Authors: Hui Dong, Zhuanzhuan Qiang, Dongdong Chai, Jiali Peng, Yangyang Xia, Rong Hu, and Hong Jiang 1: Optimizing future well-being with artificial intelligence: self-organizing maps (SOMs) for the identification of islands of emotional stability DOI: https://doi.org/10.18632/aging.204061 Authors: Fedor Galkin, Kirill Kochetov, Michelle Keller, Alex Zhavoronkov, and Nancy Etcoff ____________________ 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​​.

A new research paper was published in Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) Volume 15, Issue 3, entitled, “Epigenetic age and lung cancer risk in the CLUE II prospective cohort study.” Epigenetic age, a robust marker of biological aging, has been associated with obesity, low-grade inflammation and metabolic diseases. However, few studies have examined associations between different epigenetic age measures and risk of lung cancer, despite great interest in finding biomarkers to assist in risk stratification for lung cancer screening. In a recent study, researchers Dominique S. Michaud, Mei Chung, Naisi Zhao, Devin C. Koestler, Jiayun Lu, Elizabeth A. Platz, and Karl T. Kelsey from Tufts University, University of Kansas Medical Center, Johns Hopkins Bloomberg School of Public Health, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, and Brown University conducted a nested case-control analysis of 208 lung cancer cases and 208 matched controls with archived pre-diagnostic blood samples (from 1989). The case-control study is nested in the CLUE II cohort study, a predominantly White cohort of men and women, based in Maryland, USA. “It is important to examine whether epigenetic age is associated with lung cancer risk across multiple prospective studies to determine its utility as a potential biomarker to be considered for risk stratification in the selection of high-risk individuals for lung cancer screening.” Prediagnostic blood samples were collected in 1989 (CLUE II study baseline) and stored at −70°C. DNA was extracted from buffy coat and DNA methylation levels were measured using Illumina MethylationEPIC BeadChip Arrays. Three epigenetic age acceleration (i.e., biological age is greater than chronological age) measurements (Horvath, Hannum and PhenoAge) were examined in relation to lung cancer risk using conditional logistic regression. The researchers did not observe associations between the three epigenetic age acceleration measurements and risk of lung cancer overall; however, inverse associations for the two Hannum age acceleration measures (intrinsic and extrinsic) were observed in men and among younger participants, but not in women or older participants. Additionally, they did not observe effect modification by time from blood draw to diagnosis. “Findings from this study do not support a positive association between three different biological age acceleration measures and risk of lung cancer. Additional studies are needed to address whether epigenetic age is associated with lung cancer in never smokers.” Read the Full Paper: DOI: https://doi.org/10.18632/aging.204501 Corresponding Author: Dominique S. Michaud - Dominique.Michaud@tufts.edu Keywords: DNA methylation, epigenetic clocks, lung cancer, cohort study Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204501 About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/

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 15, Issue 3, entitled, “Immune-mediated platelet depletion augments Alzheimer’s disease neuropathological hallmarks in APP-PS1 mice.” In Alzheimer’s disease (AD), platelets become dysfunctional and might contribute to amyloid beta deposition. In a recent study, researchers Diana M. Bessa de Sousa, Ariane Benedetti, Barbara Altendorfer, Heike Mrowetz, Michael S. Unger, Katharina Schallmoser, Ludwig Aigner, and Kathrin Maria Kniewallner from Paracelsus Medical University and Austrian Cluster for Tissue Regeneration in Austria depleted platelets in one-year-old APP Swedish PS1 dE9 (APP-PS1) transgenic mice for five days, using intraperitoneal injections of an anti-CD42b antibody, and assessed changes in cerebral amyloidosis, plaque-associated neuritic dystrophy and gliosis. “The potential role of platelets in amyloid beta deposition led to the hypothesis that reducing platelet numbers might ameliorate AD pathology [30]. Here, we performed immune-mediated platelet depletion in APP-PS1 mice with an already fully developed amyloidosis and investigated its effects on classical hallmarks of AD: amyloid plaque pathology, plaque-associated neuritic dystrophy and gliosis.” In APP-PS1 female mice, platelet depletion shifted amyloid plaque size distribution towards bigger plaques and increased neuritic dystrophy in the hippocampus. In platelet-depleted females, plaque-associated Iba1+ microglia had lower amounts of fibrillar amyloid beta cargo and GFAP+ astrocytic processes showed a higher overlap with thioflavin S+ amyloid plaques. In contrast to the popular hypothesis that platelets foster plaque pathology, data from this study suggest that platelets might limit plaque growth and attenuate plaque-related neuritic dystrophy at advanced stages of amyloid plaque pathology in APP-PS1 female mice. Whether the changes in amyloid plaque pathology are due to a direct effect on amyloid beta deposition or are a consequence of altered glial function needs to be further elucidated. “In APP-PS1 females, acute thrombocytopenia aggravates AD neuropathology, suggesting that platelets might have a protective function in AD. However, the underlying molecular mechanisms by which platelets modulate amyloid plaque deposition remain elusive and need to be investigated in future experiments.” DOI: https://doi.org/10.18632/aging.204502 Corresponding Author: Kathrin Maria Kniewallner - kathrin.drerup@pmu.ac.at Keywords: Alzheimer’s disease, platelets, amyloid-beta, microglia, astrocytes Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204502 About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM