Aging-US

A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 13, entitled, “Cognitive rescue in aging through prior training in rats.” Cognitive decline in spatial memory is seen in aging. Understanding affected processes in aging is vital for developing methods to improve wellbeing. Daily memory persistence can be influenced by events around the time of learning or by prior experiences in early life. Fading memories in young can last longer if a novel event is introduced around encoding, a process called behavioral tagging. In this new study based on this principle, researchers Alexandra Gros and Szu-Han Wang from The University of Edinburgh asked what processes are affected in aging and if prior training can rescue them. “Here we asked if cognitive training in young and mid-life would improve cognitive aging and which elements of the cognitive processes at old age are preferentially protected through such training.” Two groups of aged rats received training in an appetitive delayed matching-to-place task. One of the groups additionally received prior training of the same task in young and in mid-life, constituting a longitudinal study. The results showed long-term memory decline in late aging without prior training. This would reflect affected encoding and consolidation. On the other hand, short-term memory was preserved and novelty at memory reactivation and reconsolidation enabled memory maintenance in aging. Prior training improved cognition by facilitating task performance, strengthening short-term and intermediate memory, and enabling encoding-boosted long-term memory. Learning ability, short-term memories, motor and motivation functions remained intact in older age, suggesting a phase when memory-associated processes are compromised before apparent navigation or learning deficits in advanced aging. Overall, the study's findings suggest a selective impairment in encoding for long-term memory formation in early aging and an additional impairment in consolidation in later aging. “Prior training shows profound benefits in cognitive aging and it can provide a translatable model to simulate human cognition which is built upon lifelong experiences.” DOI - https://doi.org/10.18632/aging.204808 Corresponding author - Szu-Han Wang - s.wang@ed.ac.uk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204808 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, memory consolidation, reconsolidation, memory modulation, lifelong training, cognitive stimulation About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 13, entitled, “Budding uninhibited by benzimidazoles-1 (BUB1) regulates EGFR signaling by reducing EGFR internalization.” EGFR signaling initiates upon ligand binding which leads to activation and internalization of the receptor-ligand complex. In this new study, researchers Shyam Nyati, Grant Young, Corey Speers, Mukesh K. Nyati, and Alnawaz Rehemtulla from the University of Michigan, Henry Ford Health System and Case Western Reserve University evaluated if BUB1 impacted EGFR signaling by regulating EGFR receptor internalization and activation. “We postulate that BUB1 helps in the formation and stabilization of EGFR dimers at the membrane and may regulate endocytosis of activated EGFR into either clathrin dependent (EEA1 coated) or independent (caveolin coated) vesicles thus impacting receptor recycling or degradation and subsequently signaling amplitude and duration [38, 39].” BUB1 was ablated genomically (siRNA) or biochemically (2OH-BNPP1) in cells. EGF ligand was used to initiate EGFR signaling while disuccinimidyl suberate (DSS) was used for cross linking cellular proteins. EGFR signaling was measured by western immunoblotting and receptor internalization was evaluated by fluorescent microscopy (pEGFR (pY1068) colocalization with early endosome marker EEA1). siRNA mediated BUB1 depletion led to an overall increase in total EGFR levels and more phospho-EGFR (Y845, Y1092, and Y1173) dimers while the amount of total EGFR (non-phospho) dimers remained unchanged. BUB1 inhibitor (BUB1i) decreased EGF mediated EGFR signaling including pEGFR Y845, pAKT S473 and pERK1/2 in a time dependent manner. Additionally, BUB1i also reduced EGF mediated pEGFR (Y845) dimers (asymmetric dimers) without affecting total EGFR dimers (symmetric dimers) indicating that dimerization of inactive EGFR is not affected by BUB1. Furthermore, BUB1i blocked EGF mediated EGFR degradation (increase in EGFR half-life) without impacting half-lives of HER2 or c-MET. BUB1i also reduced co-localization of pEGFR with EEA1 positive endosomes suggesting that BUB1 might modulate EGFR endocytosis. “Our data provide evidence that BUB1 protein and its kinase activity may regulate EGFR activation, endocytosis, degradation, and downstream signaling without affecting other members of the receptor tyrosine kinase family.” DOI - https://doi.org/10.18632/aging.204820 Corresponding authors - Shyam Nyati - snyati1@hfhs.org, and Alnawaz Rehemtulla - alnawaz@umich.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204820 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, BUB1, EGFR, cancer, signaling, endocytosis About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new editorial paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 12, entitled, “Advancing screening for cognitive impairment: the memtrax continuous recognition test.” Extensive efforts to find a treatment for Alzheimer’s disease (AD) span over 40 years, with the often-repeated request for better means to assess the principal dysfunction of this disease, memory impairment. Tremendous costs and resources have already been consumed in the development of treatments for this prevalent and well recognized condition, e.g., over $40 billion. These pervasive failures support the urgent need for instruments far superior to those used even in recent studies. The critical impairment in AD is a disorder of neuroplasticity. Thus, cognitive tests which can rapidly, sensitively, frequently, inexpensively, and precisely measure the aspects of memory specifically attacked by AD are principally needed. In this new editorial, researchers J. Wesson Ashford, James O. Clifford and Michael F. Bergeron from Stanford University discuss a continuous recognition test of memory called MemTrax that has been developed to quickly and accurately quantify memory processing, storage and rate of retrieval. “The precision of MemTrax would best improve the specification of the severity of cognitive impairment in early phases of Alzheimer’s disease, a period of this disease when paper and pencil and historical recollection only provide poor estimates of function [4].” Further, MemTrax can precisely assess the rate of change over time with repeat testing. By assessing performance metrics and rate of recognition response, MemTrax can screen for many varieties of cognitive impairment and thus would be an ideal tool for use in the elderly U.S. population for the Medicare Annual Wellness Visit. With a test such as MemTrax or other effective online testing, populations can be broadly and inexpensively assessed for AD-related cognitive impairment and then brought into clinical studies to determine what environmental, genetic, or interventional remedies can prevent further development of AD and the pace and/or extent of cognitive decline. “MemTrax is especially well suited for assessment of very early AD, including early mild cognitive impairment, a time when the focus should be on prevention of AD pathology, not removal of AD pathology.” DOI - https://doi.org/10.18632/aging.204828 Corresponding author - J. Wesson Ashford - ashford@stanford.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204828 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Alzheimer’s disease, memory, online testing, response time, continuous recognition test 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

In a groundbreaking study, researchers have unlocked a new frontier in the fight against aging and age-related diseases. The study, conducted by a team of scientists at Harvard Medical School, has published the first chemical approach to reprogram cells to a younger state. Previously, this was only achievable using a powerful gene therapy. On July 12, 2023, researchers 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 from Harvard Medical School, University of Maine and Massachusetts Institute of Technology (MIT) published a new research paper in Aging, titled, “Chemically induced reprogramming to reverse cellular aging.” The team's findings build upon the discovery that the expression of specific genes, called Yamanaka factors, could convert adult cells into induced pluripotent stem cells (iPSCs). This Nobel Prize-winning discovery raised the question of whether it might be possible to reverse cellular aging without causing cells to become too young and turn cancerous. In this new study, the researchers screened for molecules that could, in combination, reverse cellular aging and rejuvenate human cells. They developed high-throughput cell-based assays to distinguish young cells from old and senescent cells, including transcription-based aging clocks and a real-time nucleocytoplasmic protein compartmentalization (NCC) assay. In an exciting discovery, the team has identified six chemical cocktails that restore NCC and genome-wide transcript profiles to youthful states and reverse transcriptomic age in less than a week. The Harvard researchers previously demonstrated that it is indeed possible to reverse cellular aging without uncontrolled cell growth by virally-introducing specific Yamanaka genes into cells. Studies on the optic nerve, brain tissue, kidney, and muscle have shown promising results, with improved vision and extended lifespan observed in mice and, recently, a report of improved vision in monkeys. The implications of this new discovery are far-reaching, opening avenues for regenerative medicine and, potentially, whole-body rejuvenation. By developing a chemical alternative to age reversal via gene therapy, this research could revolutionize the treatment of aging, injuries and age-related diseases and offers the potential for lower costs and shorter timelines in development. On the heels of positive results in reversing blindness in monkeys in April 2023, preparations for human clinical trials of the lab’s age reversal gene therapy are in progress. “Until recently, the best we could do was slow aging. New discoveries suggest we can now reverse it,” said David A. Sinclair, A.O., Ph.D., Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School and lead scientist on the project. “This process has previously required gene therapy, limiting its widespread use.” The team at Harvard envisions a future where age-related diseases can be effectively treated, injuries can be repaired more efficiently, and the dream of whole-body rejuvenation becomes a reality. “This new discovery offers the potential to reverse aging with a single pill, with applications ranging from improving eyesight to effectively treating numerous age-related diseases,” Sinclair said. Press Release: https://www.aging-us.com/news_room/NEW-STUDY-Discovery-of-Chemical-Means-to-Reverse-Aging-and-Restore-Cellular-Function DOI: https://doi.org/10.18632/aging.204896 Corresponding Author: David A. Sinclair - david_sinclair@hms.harvard.edu Visit https://www.Aging-US.com​​ and connect with us on social media. MEDIA@IMPACTJOURNALS.COM

New research continues to illuminate the far-reaching implications of the gut microbiome and its crucial role in our overall health. The term “gut dysbiosis” refers to an imbalance of healthy and unhealthy microbes in the gastrointestinal tract. Repercussions of gut dysbiosis are not only limited to innocuous discomfort—it can lead to immune dysregulation and trigger a cascade of various disease states. In a new editorial paper, researchers Chun-Che Hung, Kristi M. Crowe-White and Ian M. McDonough from Chang Gung University and The University of Alabama discuss the relationship between gut dysbiosis and neurocognitive disorders such as Alzheimer’s disease (AD). Their editorial was published in Aging’s Volume 15, Issue 12, on June 19, 2023, entitled, “A seed and soil model of gut dysbiosis in Alzheimer’s disease.” “[…] recent research has demonstrated a crucial role of gut microbiota in the etiopathogenesis of AD [Alzheimer’s disease] that offers a new window into possible origins and consequences of AD through interactions between gut microbiota and the central nervous system, known as the ‘microbiota-gutbrain axis’ [1].” Full blog - https://aging-us.org/2023/07/can-a-leaky-gut-lead-to-alzheimers-disease/ Paper DOI - https://doi.org/10.18632/aging.204840 Corresponding author - Ian M. McDonough - immcdonough@ua.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204840 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Alzheimer’s disease, neurocognitive disorders, gut-brain axis, gut microbiota, dysbiosis About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 12, entitled, “Hepatic hydrogen sulfide levels are reduced in mouse model of Hutchinson-Gilford progeria syndrome.” Hutchinson-Gilford progeria syndrome (HGPS) is a rare human disease characterized by accelerated biological aging. Current treatments are limited, and most patients die before 15 years of age. Hydrogen sulfide (H2S) is an important gaseous signaling molecule that is central to multiple cellular homeostasis mechanisms. Dysregulation of tissue H2S levels is thought to contribute to an aging phenotype in many tissues across animal models. Whether H2S is altered in HGPS is unknown. In a new study, researchers Stephen E. Wilkie, Diana E. Marcu, Roderick N. Carter, Nicholas M. Morton, Susana Gonzalo, and Colin Selman from the University of Glasgow, University of Edinburgh, Saint Louis University, and Karolinska Institute investigated hepatic H2S production capacity and transcript, protein and enzymatic activity of proteins that regulate hepatic H2S production and disposal in a mouse model of HGPS (G609G mice, mutated Lmna gene equivalent to a causative mutation in HGPS patients). “This study was designed and undertaken due to the lack of understanding in the mechanistic targets of known treatments against HGPS and considering the positive association between H2S and longevity in model organisms.” Here, the researchers employed the HGPS mouse model G609G to test the hypothesis that, in contrast to anti-aging increases in H2S production, the accelerated aging typical of progeroid mice is associated with reduced hepatic H2S production. G609G mice were maintained on either regular chow (RC) or high fat diet (HFD). HFD has been previously shown to significantly extend lifespan of G609G mice, and compared to wild type (WT) mice maintained on RC. RC-fed G609G mice had significantly reduced hepatic H2S production capacity relative to WT mice, with a compensatory elevation in mRNA transcripts associated with several H2S production enzymes, including cystathionine-γ-lyase (CSE). H2S levels and CSE protein were partially rescued in HFD fed G609G mice. The data acquired here confirmed some aspects of the relevance of H2S in HGPS but raises more questions about the specific mechanisms at play. “Regardless, the work presented here addresses an area of research that remains critically understudied and provides new evidence that the accelerated ageing phenotype observed in HGPS may be partially explained by a reduction in hepatic H2S levels.” DOI - https://doi.org/10.18632/aging.204835 Corresponding authors - Colin Selman - colin.selman@glasgow.ac.uk, and Stephen E. Wilkie - stephen.wilkie@ki.se Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204835 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, progeria, hydrogen sulfide, high-fat diet, ageing, lamin A About Aging-US: Launched in 2009, Aging publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com​​ and connect with us on social media. MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (Aging-US) Volume 15, Issue 12, entitled, “A novel peptide ‘T14’ reflects age and photo-aging in human skin.” T14 is a 14mer peptide derived from the C-terminus of acetylcholinesterase (AChE). Once cleaved, it is independently bioactive of the parent molecule and enhances calcium influx in different cell types, in a range of scenarios: it binds to an allosteric site selectively on the alpha-7 receptor, where it modulates calcium influx and is thus a potential trophic agent, as already reported in a range of normal developmental scenarios. However, if inappropriately activated, this erstwhile beneficial effect converts to a toxic one, resulting in pathologies as disparate as Alzheimer’s and various metastatic cancers. In this new study, given that epidermal keratinocyte cells have the same ectodermal origin as brain cells, as well as expressing AChE and the alpha-7 receptor, researchers Sheila Rocha, Sara Garcia Ratés, Tumisang Moswete, Kristopher Kalleberg, Anna Villa, Jason P. Harcup, and Susan A. Greenfield from Unilever Research and Development and Neuro-Bio explored whether T14 plays a comparable role. “The first aim of this study was therefore to see if T14-ir could be detected in keratinocytes using an antibody that would not recognize the parent AChE itself, and thus be readily differentiated from it. [...] Hence the second aim of the study was to investigate the possibility that T14 was not only present in keratinocytes but could be regarded as an index reflecting not just age but also photo-induced aging.” The team reports that the T14 immunoreactivity is detectable in human keratinocytes with levels inversely related to age: this decrease is even more apparent with chronic photo-exposure and thus accelerated skin aging. They concluded that T14, an agent promoting cell growth and renewal in other parts of the body, also operates in skin. Moreover, monitoring of keratinocyte T14 levels might offer further insights into the now well reported link between degenerative diseases and epidermal cell profile. “Hence further exploration of the T14 system in the epidermis might prompt new insights into the treatment of hyperproliferative skin disorders, as well as into the mechanisms of normal skin age and ageing.” DOI - https://doi.org/10.18632/aging.204844 Corresponding author - Sara Garcia Ratés - sara.garciarates@neuro-bio.com Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204844 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, skin, photo-aging, acetylcholinesterase peptide, keratinocyte About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published on the cover of Aging (Aging-US) Volume 15, Issue 12, entitled, “Age prediction from human blood plasma using proteomic and small RNA data: a comparative analysis.” Aging clocks, built from comprehensive molecular data, have emerged as promising tools in medicine, forensics, and ecological research. However, few studies have compared the suitability of different molecular data types to predict age in the same cohort and whether combining them would improve predictions. In this new study, researchers Jérôme Salignon, Omid R. Faridani, Tasso Miliotis, Georges E. Janssens, Ping Chen, Bader Zarrouki, Rickard Sandberg, Pia Davidsson, and Christian G. Riedel from Karolinska Institutet, University of New South Wales, Garvan Institute of Medical Research, and AstraZeneca explored this at the level of proteins and small RNAs in 103 human blood plasma samples. “Here we expand the limited portfolio of comparisons between aging clocks built from different types of molecular data from the same cohort.” First, the researchers used a two-step mass spectrometry approach measuring 612 proteins to select and quantify 21 proteins that changed in abundance with age. Notably, proteins increasing with age were enriched for components of the complement system. Next, they used small RNA sequencing to select and quantify a set of 315 small RNAs that changed in abundance with age. Most of these were microRNAs (miRNAs), downregulated with age, and predicted to target genes related to growth, cancer, and senescence. Finally, the team used the collected data to build age-predictive models. Among the different types of molecules, proteins yielded the most accurate model (R² = 0.59 ± 0.02), followed by miRNAs as the best-performing class of small RNAs (R² = 0.54 ± 0.02). Interestingly, the use of protein and miRNA data together improved predictions (R2 = 0.70 ± 0.01). Future work using larger sample sizes and a validation dataset will be necessary to confirm these results. “Nevertheless, our study suggests that combining proteomic and miRNA data yields superior age predictions, possibly by capturing a broader range of age-related physiological changes. It will be interesting to determine if combining different molecular data types works as a general strategy to improve future aging clocks.” DOI - https://doi.org/10.18632/aging.204787 Corresponding author - Christian G. Riedel - christian.riedel@ki.se Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204787 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, human blood plasma, small RNAs, proteomics, age prediction About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (Aging-US) Volume 15, Issue 11, entitled, “Senescence and senotherapies in biliary atresia and biliary cirrhosis.” Premature senescence occurs in adult hepatobiliary diseases and worsens the prognosis through deleterious liver remodeling and hepatic dysfunction. Senescence might also arise in biliary atresia (BA), the first cause of pediatric liver transplantation. Alternatives to transplantation are needed. In this new study, researchers Giulia Jannone, Eliano Bonaccorsi Riani, Catherine de Magnée, Roberto Tambucci, Jonathan Evraerts, Joachim Ravau, Pamela Baldin, Caroline Bouzin, Axelle Loriot, Laurent Gatto, Anabelle Decottignies, Mustapha Najimi, and Etienne Marc Sokal from the Université catholique de Louvain in Brussels, Belgium, aimed to investigate premature senescence in BA and to assess senotherapies in a preclinical model of biliary cirrhosis. “As there is a need for new therapies to avoid or delay liver transplantation in pediatric biliary cirrhosis, the aim of our work was to investigate premature senescence in BA through a multi-technical approach and to assess senotherapies in a preclinical model of biliary cirrhosis.” BA liver tissues were prospectively obtained at hepatoportoenterostomy (n=5) and liver transplantation (n=30) and compared to controls (n=10). Senescence was investigated through spatial whole transcriptome analysis, SA-β-gal activity, p16 and p21 expression, γ-H2AX and senescence-associated secretory phenotype (SASP). Human allogenic liver-derived progenitor cells (HALPC) or dasatinib and quercetin (D+Q) were administered to two-month-old Wistar rats after bile duct ligation (BDL). Advanced premature senescence was evidenced in BA livers from early stage and continued to progress until liver transplantation. Senescence and SASP were predominant in cholangiocytes, but also present in surrounding hepatocytes. HALPC but not D+Q reduced the early marker of senescence p21 in BDL rats and improved biliary injury (serum γGT and Sox9 expression) and hepatocytes mass loss (Hnf4a). “BA livers displayed advanced cellular senescence at diagnosis that continued to progress until liver transplantation. HALPC reduced early senescence and improved liver disease in a preclinical model of BA, providing encouraging preliminary results regarding the use of senotherapies in pediatric biliary cirrhosis.” DOI - https://doi.org/10.18632/aging.204700 Corresponding author - Giulia Jannone - giulia.jannone@uclouvain.be Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204700 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, senotherapy, liver, biliary cirrhosis, biliary atresia About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (Aging-US) Volume 15, Issue 11, entitled, “Old-age-induced obesity reversed by a methionine-deficient diet or oral administration of recombinant methioninase-producing Escherichia coli in C57BL/6 mice.” Obesity increases with aging. Methionine restriction affects lipid metabolism and can prevent obesity in mice. In this new study, researchers Yutaro Kubota, Qinghong Han, Jose Reynoso, Yusuke Aoki, Noriyuki Masaki, Koya Obara, Kazuyuki Hamada, Michael Bouvet, Takuya Tsunoda, and Robert M. Hoffman from AntiCancer Inc., University of California San Diego and Showa University School of Medicine observed C57BL/6 mice double their body weight from 4 to 48 weeks of age and become obese. The team then evaluated the efficacy of oral administration of recombinant-methioninase (rMETase)-producing E. coli (E. coli JM109-rMETase) or a methionine-deficient diet to reverse old-age-induced obesity in C57BL/6 mice. “In the present study we tested a low-methionine diet to reverse old-age-induced obesity. [...] E. coli JM109-rMETase was also tested in the present study to reverse old-age-induced obesity.” Fifteen C57BL/6 male mice aged 12–18 months with old-age-induced obesity were divided into three groups. Group 1 was given a normal diet supplemented with non-recombinant E. coli JM109 cells orally by gavage twice daily; Group 2 was given a normal diet supplemented with recombinant E. coli JM109-rMETase cells by gavage twice daily; and Group 3 was given a methionine-deficient diet without treatment. The administration of E. coli JM109-rMETase or a methionine-deficient diet reduced the blood methionine level and reversed old-age-induced obesity with significant weight loss by 14 days. There was a negative correlation between methionine levels and negative body weight change. Although the degree of efficacy was higher in the methionine-deficient diet group than in the E. coli JM109-rMETase group, the present findings suggested that oral administration of E. coli JM109-rMETase, as well as a methionine-deficient diet, are effective in reversing old-age-induced obesity. “In conclusion, the present study provides evidence that restricting methionine by either a low-methionine diet or E. coli JM109-rMETase has clinical potential to treat old-age-induced obesity.” DOI - https://doi.org/10.18632/aging.204783 Corresponding author - Robert M. Hoffman - all@anticancer.com Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204783 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, obesity, methionine restriction, methionine-deficient diet, recombinant methioninase (rMETase), Escherichia coli, microbiome, weight-loss 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