A traditional, twice-monthly, peer-reviewed, open-access journal covering all areas of research on aging and age-related diseases, including cancer and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome.

In June 2022, Web of Science (Clarivate Analytics) released their 2021 JCR Impact Factor List. Aging is pleased to report that our 2021 impact factor is 5.955. This number has increased from last year’s 5.682.

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Aging (Aging-US)

Aging-US published this research paper as the cover of Volume 14, Issue 22, entitled, "Glutaminase inhibitors rejuvenate human skin via clearance of senescent cells: a study using a mouse/human chimeric model" by researchers from the Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo, Japan.

DOI - https://doi.org/10.18632/aging.204391

Corresponding author - Kento Takaya - kento-takaya312@keio.jp

Abstract

Skin aging caused by various endogenous and exogenous factors results in structural and functional changes to skin components. However, the role of senescent cells in skin aging has not been clarified. To elucidate the function of senescent cells in skin aging, we evaluated the effects of the glutaminase inhibitor BPTES (bis-2-(5-phenylacetamido-1, 3, 4-thiadiazol-2-yl)ethyl sulfide) on human senescent dermal fibroblasts and aged human skin. Here, primary human dermal fibroblasts (HDFs) were induced to senescence by long-term passaging, ionizing radiation, and treatment with doxorubicin, an anticancer drug. Cell viability of HDFs was assessed after BPTES treatment. A mouse/human chimeric model was created by subcutaneously transplanting whole skin grafts from aged humans into nude mice. The model was treated intraperitoneally with BPTES or vehicle for 30 days. Skin samples were collected and subjected to reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, and histological analysis. BPTES selectively eliminated senescent dermal fibroblasts regardless of the method used to induce senescence; aged human skin grafts treated with BPTES exhibited increased collagen density, increased cell proliferation in the dermis, and decreased aging-related secretory phenotypes, such as matrix metalloprotease and interleukin. These effects were maintained in the grafts 1 month after termination of the treatment. In conclusion, selective removal of senescent dermal fibroblasts can improve the skin aging phenotype, indicating that BPTES may be an effective novel therapeutic agent for skin aging.

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Press release - https://www.aging-us.com/news_room/glutaminase-inhibitors-rejuvenate-human-skin-via-clearance-of-senescent-cells-a-study-using-a-mouse-human-chimeric-model

Keywords - aging, glutaminase inhibitor, human skin, senescent cell, therapeutic agent

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.

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Glutaminase Inhibitors Rejuvenate Human Skin via Clearance of Senescent Cells

Aging (Aging-US) published this trending research paper in Volume 14, Issue 21, entitled, “Krill oil protects dopaminergic neurons from age-related degeneration through temporal transcriptome rewiring and suppression of several hallmarks of aging” by researchers from the Institute of Clinical Medicine, Department of Clinical Molecular Biology, University of Oslo, Oslo N-0318, Norway; Section of Clinical Molecular Biology, Akershus University Hospital, Nordbyhagen N-1474, Norway; Department of Microbiology, Oslo University Hospital, Oslo N-0424, Norway; Department of Biosciences, University of Oslo, Oslo N-0318, Norway.

DOI - https://doi.org/10.18632/aging.204375

Corresponding author - Hilde Nilsen - hilde.nilsen@medisin.uio.no 

ABSTRACT

There is accumulating evidence that interfering with the basic aging mechanisms can enhance healthy longevity. The interventional/therapeutic strategies targeting multiple aging hallmarks could be more effective than targeting one hallmark. While health-promoting qualities of marine oils have been extensively studied, the underlying molecular mechanisms are not fully understood. Lipid extracts from Antarctic krill are rich in long-chain omega-3 fatty acids choline, and astaxanthin. Here, we used C. elegans and human cells to investigate whether krill oil promotes healthy aging. In a C. elegans model of Parkinson´s disease, we show that krill oil protects dopaminergic neurons from aging-related degeneration, decreases alpha-synuclein aggregation, and improves dopamine-dependent behavior and cognition. Krill oil rewires distinct gene expression programs that contribute to attenuating several aging hallmarks, including oxidative stress, proteotoxic stress, senescence, genomic instability, and mitochondrial dysfunction. Mechanistically, krill oil increases neuronal resilience through temporal transcriptome rewiring to promote anti-oxidative stress and anti-inflammation via healthspan regulating transcription factors such as SNK-1. Moreover, krill oil promotes dopaminergic neuron survival through regulation of synaptic transmission and neuronal functions via PBO-2 and RIM-1. Collectively, krill oil rewires global gene expression programs and promotes healthy aging via abrogating multiple aging hallmarks, suggesting directions for further pre-clinical and clinical explorations.

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Keywords - krill oil, aging, healthspan, mitochondrial health, senescence

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.

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Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​

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Krill Oil Protects Dopaminergic Neurons From Age-Related Degeneration

Aging (Aging-US) published this trending research paper in Volume 14, Issue 21, entitled, “The deubiquitylase USP7 is a novel cyclin F-interacting protein and regulates cyclin F protein stability” by researchers from the Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bengaluru, India; Sri Shankara Cancer Hospital and Research Centre, Bengaluru, India; Department of Surgery, University of Utah Health, Huntsman Cancer Institute, Salt Lake City, UT.

DOI - https://doi.org/10.18632/aging.204372

Corresponding author - Savitha S. Sharma - savitha.sharma@ssnccpr.org

ABSTRACT

Cyclin F, unlike canonical and transcriptional cyclins, does not bind or activate any cyclin-dependent kinases. Instead, it harbors an F-box motif and primarily functions as the substrate recognition subunit of the Skp1-Cul1-F-box E3 ubiquitin ligase complex, SCFCyclin F. By targeting specific proteins for ubiquitin-mediated proteasomal degradation, cyclin F plays a critical role in the regulation of centrosomal duplication, DNA replication and repair, and maintenance of genomic stability. Cyclin F abundance and activity are tightly regulated throughout the cell cycle. However, the molecular mechanisms regulating cyclin F are scantily understood. Here, we identify the deubiquitylase USP7 as a novel cyclin F-interacting protein. We observe that USP7 stabilizes cyclin F protein and that this function is independent of the deubiquitylase activity of USP7. Additionally, our data suggest that USP7 is also involved in the regulation of cyclin F mRNA. Pharmacological inhibition of the deubiquitylase activity of USP7 resulted in downregulation of cyclin F mRNA.

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Keywords - cyclin F, atypical cyclins, USP7, cell cycle, genomic integrity

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.

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Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​

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USP7 Regulates Cyclin F Protein Stability

Aging-US published this trending research paper in Volume 14, Issue 21, entitled, "ESR1 dysfunction triggers neuroinflammation as a critical upstream causative factor of the Alzheimer’s disease process" by researchers from NatPro Center, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Ireland; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China; Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, Changchun, China; School of Medicine, Trinity College Dublin, Ireland.

DOI - https://doi.org/10.18632/aging.204359

Corresponding authors - Junying Liu - juliu@tcd.ie 

Abstract

Alzheimer's disease (AD) accounts for approximately 60% of dementia cases worldwide. Advanced age is the most significant risk factor for AD and approximately two-thirds of cases relate to women. While the previous meta-analysis suggests that estrogen receptor (ESR) genetic polymorphisms are closely associated with dementia, the implications of this observation on a molecular level are not entirely understood. Our study explores this intricate molecular puzzle through the use of a variety of bioinformatics tools. Initially, we attempted to elucidate mechanisms underlying breast cancer development by identifying the high-throughput dataset of ESR1-knockdown breast cancer tissue samples. Surprisingly, KEGG pathway enrichment showed that the most frequently occurring proteins were related to axonal guidance and inflammation-related gene markers. These observations were supported by an external high throughput dataset of AD inflammatory samples in vivo. Our results suggest that ESR1 is modulated by apolipoprotein E (APOE) through CEBPB/ATF4, mir-155-5p, or mir-1-3p. Moreover, sea hare-hydrolysates (SHH), as one of the axonal guidance molecules, could regulate the STAT3/PRDM1/CEBPB pathway and consequently induce cell death through pyroptosis signaling pathways, trigger the secretion of IL1β, leading to neuroinflammation and worsening AD pathogenesis. Molecular docking verification demonstrated that the predicted natural products scoulerine and genistein displayed strong binding affinities for BACE1 and ESR1, respectively. This strategy can be used to design novel, personalized therapeutic approaches to treatment and a first-in-class clinical lead for the personalised treatment of AD.

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Keywords - ESR1, Alzheimer’s disease, CEBPB/ATF4, APOE, pyroptosis

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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ESR1: A Critical Factor in the Alzheimer’s Disease Process

Aging-US published this research paper as the cover of Volume 14, Issue 21, entitled, "IGF1 gene therapy in middle-aged female rats delays reproductive senescence through its effects on hypothalamic GnRH and kisspeptin neurons" by researchers from the Laboratorio de Bioquímica del Envejecimiento, Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), Facultad de Ciencias Médicas, UNLP-CONICET, La Plata, Argentina; Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata, Argentina; Instituto de Farmacología Experimental de Córdoba-CONICET, Departamento de Farmacología, Facultad de Ciencias Químicas, UNC-CONICET, Córdoba, Argentina; Department of Anatomy, Histology and Neuroscience, Autonomous University of Madrid, Madrid, España; Instituto Cajal, CSIC, Madrid, España; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, España.

DOI - https://doi.org/10.18632/aging.204360

Corresponding authors - Maria-Angeles Arevalo - arevalo@cajal.csic.es, and María José Bellini - mariajosebellini@med.unlp.edu.ar

Abstract

The process of aging is the result of progressive loss of homeostasis and functional body impairment, including the central nervous system, where the hypothalamus plays a key role in regulating aging mechanisms. The consequences of aging include a chronic proinflammatory environment in the hypothalamus that leads to decreased secretion of gonadotropin-releasing hormone (GnRH) and impairs kisspeptin neuron functionality.

In this work, we investigated the effect of insulin-like growth factor 1 (IGF1) gene therapy on hypothalamic kisspeptin/GnRH neurons and on microglial cells, that mediate the inflammatory process related with the aging process. The results show that IGF1 rats have higher kisspeptin expression in the anteroventral periventricular (AVPV) nucleus and higher immunoreactivity of GnRH in the arcuate nucleus and median eminence. In addition, IGF1-treated animals exhibit increased numbers of Iba1+ microglial cells and MHCII+/Iba1+ in the AVPV and arcuate nuclei. In conclusion, IGF1 gene therapy maintains kisspeptin production in the AVPV nucleus, induces GnRH release in the median eminence, and alters the number and reactivity of microglial cells in middle-aged female rats. We suggest that IGF1 gene therapy may have a protective effect against reproductive decline.

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Keywords - aging, IGF1, gene therapy, reproductive senescence, GnRH, kisspeptin, microglia

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:

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IGF1 Gene Therapy in Middle-Aged Female Rats Delays Reproductive Senescence

Aging (Aging-US) published this trending research paper in Volume 14, Issue 20, entitled, “Age-associated changes in microglia activation and Sirtuin-1- chromatin binding patterns” by researchers from San Diego Biomedical Research Institute, San Diego, CA; University of Nebraska Medical Center, Omaha, NE; Oncovalent Therapeutics, Los Angeles, CA.

DOI - https://doi.org/10.18632/aging.204329

Corresponding author - Maria Cecilia Garibaldi Marcondes - cmarcondes@SDBRI.org 

ABSTRACT

The aging process is associated with changes in mechanisms maintaining physiology, influenced by genetics and lifestyle, and impacting late life quality and longevity. Brain health is critical in healthy aging. Sirtuin 1 (Sirt1), a histone deacetylase with silencing properties, is one of the molecular determinants experimentally linked to health and longevity. We compared brain pathogenesis and Sirt1-chromatin binding dynamics in brain pre-frontal cortex from 2 groups of elder rhesus macaques, divided by age of necropsy: shorter-lived animals (18-20 years old (yo)), equivalent to 60-70 human yo; and longer-lived animals (23-29 yo), corresponding to 80-100 human yo and modeling successful aging. These were compared with young adult brains (4-7 yo). Our findings indicated drastic differences in the microglia marker Iba1, along with factors influencing Sirt1 levels and activity, such as CD38 (an enzyme limiting NAD that controls Sirt1 activity) and mir142 (a microRNA targeting Sirt1 transcription) between the elder groups. Iba1 was lower in shorter-lived animals than in the other groups, while CD38 was higher in both aging groups compared to young. mir142 and Sirt1 levels were inversely correlated in longer-lived brains (>23yo), but not in shorter-lived brains (18-20 yo). We also found that Sirt1 binding showed signs of better efficiency in longer-lived animals compared to shorter-lived ones, in genes associated with nuclear activity and senescence. Overall, differences in neuroinflammation and Sirt1 interactions with chromatin distinguished shorter- and longer-lived animals, suggesting the importance of preserving microglia and Sirt1 functional efficiency for longevity.

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Press release - https://www.aging-us.com/news_room/age-associated-changes-in-microglia-activation-and-sirtuin-1-chromatin-binding-patterns

Keywords - aging, brain, rhesus macaques, microglia, Sirtuin-1

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at http://www.Aging-US.com​​ and connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
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YouTube - https://www.youtube.com/agingus​
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Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​

Media Contact
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MEDIA@IMPACTJOURNALS.COM

Aging (Aging-US)

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