A new research paper was published on the cover of Aging (Aging-US) Volume 15, Issue 9, entitled, “In vitro and in vivo effects of zoledronic acid on senescence and senescence-associated secretory phenotype markers.”

Zoledronic acid has been found to reduce fracture risk and, in some studies, to decrease mortality in humans and extend lifespan and healthspan in animals. Because senescent cells accumulate with aging and contribute to multiple comorbidities, the non-skeletal actions of zoledronic acid could be due to senolytic (killing of senescent cells) or senomorphic (inhibition of the secretion of the senescence-associated secretory phenotype (SASP)) actions.

In this new study, researchers Parinya Samakkarnthai, Dominik Saul, Lei Zhang, Zaira Aversa, Madison L. Doolittle, Jad G. Sfeir, Japneet Kaur, Elizabeth J. Atkinson, James R. Edwards, Graham G. Russell, Robert J. Pignolo, James L. Kirkland, Tamar Tchkonia, Laura J. Niedernhofer, David G. Monroe, Nathan K. Lebrasseur, Joshua N. Farr, Paul D. Robbins, and Sundeep Khosla from the Mayo Clinic, Phramongkutklao Hospital and College of Medicine, Eberhard Karls University, University of Minnesota, University of Oxford, and University of Sheffield tested the above hypothesis using multiple complementary approaches (in vitro, in vivo, and in silico) to evaluate possible effects of zoledronic acid on modulating cellular senescence.

The researchers first performed in vitro senescence assays using human lung fibroblasts and DNA repair-deficient mouse embryonic fibroblasts, which demonstrated that zoledronic acid killed senescent cells with minimal effects on non-senescent cells. Next, in aged mice treated with zoledronic acid or vehicle for 8 weeks, zoledronic acid significantly reduced circulating SASP factors, including CCL7, IL-1β, TNFRSF1A, and TGFβ1 and improved grip strength. Analysis of publicly available RNAseq data from CD115+ (CSF1R/c-fms+) pre-osteoclastic cells isolated from mice treated with zoledronic acid demonstrated a significant downregulation of senescence/SASP genes (SenMayo). 

To establish that these cells are potential senolytic/senomorphic targets of zoledronic acid, the team used single cell proteomic analysis (cytometry by time of flight [CyTOF]) and demonstrated that zoledronic acid significantly reduced the number of pre-osteoclastic (CD115+/CD3e-/Ly6G-/CD45R-) cells and decreased protein levels of p16, p21, and SASP markers in these cells without affecting other immune cell populations. 

“Collectively, our findings demonstrate that zoledronic acid has senolytic effects in vitro and modulates senescence/SASP biomarkers in vivo. These data point to the need for additional studies testing zoledronic acid and/or other bisphosphonate derivatives for senotherapeutic efficacy.”

DOI - https://doi.org/10.18632/aging.204701

Corresponding author - Sundeep Khosla - khosla.sundeep@mayo.edu

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 (Aging-US)

Effects of Zoledronic Acid on Senescence and SASP Markers

BUFFALO, NY- May 21, 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 9, entitled, “Germicidal lamps using UV-C radiation may pose health safety issues: a biomolecular analysis of their effects on apoptosis and senescence.”

The battle against the COVID-19 pandemic has spurred a heightened state of vigilance in global healthcare, leading to the proliferation of diverse sanitization methods. Among these approaches, germicidal lamps utilizing ultraviolet (UV) rays, particularly UV-C (wavelength ranging from 280 to 100 nm), have gained prominence for domestic use. 

These light-emitting diode (LED) lamps are designed to sanitize the air, objects, and surfaces. However, the prevailing concern is that these UV lamps are often introduced into the market without adequate accompanying information to ensure their safe utilization. Importantly, exposure to absorbed UV light can potentially trigger adverse biological responses, encompassing cell death and senescence.

In this new study, researchers Nicola Alessio, Alessia Ambrosino, Andrea Boggi, Domenico Aprile, Iole Pinto, Giovanni Galano, Umberto Galderisi, and Giovanni Di Bernardo from the University of Campania Luigi Vanvitelli, Regional Public Health Laboratory in Siena, Italy, ASL Napoli 1 Centro P.S.I. Napoli Est-Barra, and Temple University performed a series of investigations aimed at comprehending the biological repercussions of UV-C radiation exposure from readily available domestic lamps. 

“Our focus centered on epithelial retinal cells, keratinocytes, and fibroblasts, components of the skin and ocular targets frequently exposed to UV irradiation.”

Their findings underscore the potential harm associated with even brief exposure to UV, leading to irreversible and detrimental alterations in both skin cells and retinal cells of the eye. Notably, epithelial retinal cells exhibited heightened sensitivity, marked by substantial apoptosis. In contrast, keratinocytes demonstrated resilience to apoptosis even at elevated UV doses, though they were prone to senescence. Meanwhile, fibroblasts displayed a gradual amplification of both senescence and apoptosis as radiation doses escalated.

“In summary, despite the potential benefits offered by UV-C in deactivating pathogens like SARS-CoV-2, it remains evident that the concurrent risks posed by UV-C to human health cannot be ignored.”

DOI - https://doi.org/10.18632/aging.205787

Corresponding authors - Umberto Galderisi - umberto.galderisi@unicampania.it, and Giovanni Di Bernardo - gianni.dibernardo@unicampania.it

Sign up for free Altmetric alerts about this article - 
https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205787

Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts

Keywords - aging, senescence, apoptosis, UV light, public health

About Aging-US

Aging publishes research papers in all fields of aging research, including but not limited to aging processes (from yeast to mammals), cellular senescence, age-related diseases (such as cancer and Alzheimer’s disease) and their prevention and treatment, anti-aging strategies and drug development, and, importantly, the role of signal transduction pathways in aging (such as mTOR) and potential approaches to modulate these signaling pathways to extend lifespan.

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

Germicidal Lamps Using UV-C Radiation May Pose Health Safety Issues

Dr. Leonid Peshkin from the Department of Systems Biology at Harvard Medical School details a research perspective he co-authored that was published by Aging (Aging-US) in Volume 16, Issue 4, entitled, “On standardization of controls in lifespan studies.”
#aging #author #interview #researcher#data #standardization #lifespan #longevity #study #perspective #openaccess #openscience #peerreview #journal #publication #publishing #meded #spotlight #agingshort #video

DOI - https://doi.org/10.18632/aging.205604

Corresponding author - Leonid Peshkin - pesha@hms.harvard.edu

Video interview - https://www.youtube.com/watch?v=N_tL2aTN2Jw

Interview transcript - https://aging-us.net/2024/05/22/behind-the-study-on-standardization-of-controls-in-lifespan-studies/

Abstract

The search for interventions to slow down and even reverse aging is a burgeoning field. The literature cites hundreds of supposedly beneficial pharmacological and genetic interventions in model organisms: mice, rats, flies and worms, where research into physiology is routinely accompanied by lifespan data. However, when experimental animals from one article live as long as controls from another article, comparing the results of interventions across studies can yield misleading outcomes. Theoretically, all lifespan data are ripe for re-analysis: we could contrast the molecular targets and pathways across studies and help focus the further search for interventions. Alas, the results of most longevity studies are difficult to compare. This is in part because there are no clear, universally accepted standards for conducting such experiments or even for reporting such data. The situation is worsened by the fact that the authors often do not describe experimental conditions completely. As a result, works on longevity make up a set of precedents, each of which might be interesting in its own right, yet incoherent and incomparable at least for the reason that in a general context, it may indicate, for example, not prolonging the life of an average organism, but compensating for any genetic abnormalities of a particular sample or inappropriate living conditions. Here we point out specific issues and propose solutions for quality control by checking both inter- and intra-study consistency of lifespan data.

Sign up for free Altmetric alerts about this article - 
https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205604

Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts

Keywords - aging, animal disease models, survival modeling, data standardization

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

Behind the Study: Standardization of Controls in Lifespan Studies

Behind the Study: On Standardization of Controls in Lifespan Studies

BUFFALO, NY- May 22, 2024 – A new research paper was published in Oncotarget's Volume 15 on May 17, 2024, entitled, “GZ17-6.02 kills PDX isolates of uveal melanoma.”

In this new study, researchers Laurence Booth, Jane L. Roberts, Ivan Spasojevic, Kaitlyn C. Baker, Andrew Poklepovic, Cameron West, John M. Kirkwood, and Paul Dent from Virginia Commonwealth University, Duke University School of Medicine, Genzada Pharmaceuticals, Texas Tech University Health Sciences Center, and University of Pittsburgh Cancer Institute defined the biology of GZ17-6.02 in UM cells and in parallel determined its interaction with irreversible ERBB inhibitors (afatinib, neratinib) and with the cytotoxic agent doxorubicin. 

“GZ17-6.02 is a novel compound, containing the synthetically manufactured components: curcumin, harmine and isovanillin and has undergone phase I safety evaluation in cancer patients (NCT03775525).”

GZ17-6.02 has undergone phase I evaluation in patients with solid tumors (NCT03775525). The RP2D is 375 mg PO BID, with an uveal melanoma patient exhibiting a 15% reduction in tumor mass for 5 months at this dose. Studies in this manuscript have defined the biology of GZ17-6.02 in PDX isolates of uveal melanoma cells. 

GZ17-6.02 killed uveal melanoma cells through multiple convergent signals including enhanced ATM-AMPK-mTORC1 activity, inactivation of YAP/TAZ and inactivation of eIF2α. GZ17-6.02 significantly enhanced the expression of BAP1, predictive to reduce metastasis, and reduced the levels of ERBB family RTKs, predicted to reduce growth. GZ17-6.02 interacted with doxorubicin or ERBB family inhibitors to significantly enhance tumor cell killing which was associated with greater levels of autophagosome formation and autophagic flux. 

Knock down of Beclin1, ATG5 or eIF2α were more protective than knock down of ATM, AMPKα, CD95 or FADD, however, over-expression of FLIP-s provided greater protection compared to knock down of CD95 or FADD. Expression of activated forms of mTOR and STAT3 significantly reduced tumor cell killing. GZ17-6.02 reduced the expression of PD-L1 in uveal melanoma cells to a similar extent as observed in cutaneous melanoma cells whereas it was less effective at enhancing the levels of MHCA. The components of GZ17-6.02 were detected in tumors using a syngeneic tumor model. 

“Our data support future testing GZ17-6.02 in uveal melanoma as a single agent, in combination with ERBB family inhibitors, in combination with cytotoxic drugs, or with an anti-PD1 immunotherapy.”

DOI - https://doi.org/10.18632/oncotarget.28586

Correspondence to - Paul Dent - paul.dent@vcuhealth.org

Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28586

Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/

Keywords - cancer, autophagy, ER stress, GZ17-6.02, doxorubicin, afatinib, neratinib

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

Facebook - https://www.facebook.com/Oncotarget/
X - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
YouTube - https://www.youtube.com/@OncotargetJournal
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/
Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh

MEDIA@IMPACTJOURNALS.COM

Oncotarget

GZ17-6.02 Kills Uveal Melanoma Cells

BUFFALO, NY- May 22, 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 9, entitled, “Cell type-dependent modulation of senescence features using Weo electrolyzed water.”

Electrolyzed-reduced water has powerful antioxidant properties with constituents that scavenge reactive oxygen species (ROS), which are known to be produced by several intrinsic and extrinsic processes. When there is an imbalance between ROS production and antioxidant defenses, oxidative stress occurs. Persistent oxidative stress leads to cellular senescence, an important hallmark of aging, and is involved in several age-related conditions and illnesses. 

In this new study, researchers Brenda L. Court-Vazquez, Shirley A. Arroyo-Vizcarrondo, Jonathan A. Poli, Lara Nyman, Kelly Halderman, Anthony Ginter, and Pierre-Yves Desprez from Weo LLC and California Pacific Medical Center investigated whether Weo electrolyzed water (WEW) could modulate the phenotype of senescent cells. 

“The focus of this study was to utilize two different cell types, human normal fibroblasts and human breast cancer cells, to investigate the impact of Weo electrolyzed water (WEW) on markers of cellular senescence, inflammation, and stress response genes.”

The researchers compared normal human lung fibroblasts (BJ) and breast cancer cells (T47D) treated with hydrogen peroxide (H2O2) to induce senescence. They assessed the molecular impact of WEW on markers of cellular senescence, senescence-associated secretory phenotype (SASP) factors, and stress response genes. Treatment with WEW modulated markers of cellular senescence, such as the senescence-associated β-galactosidase (SA-β-gal) activity, EdU incorporation and p21 expression, similarly in both cell types. 

However, WEW modulated the expression of SASP factors and stress response genes in a cell type-dependent and opposite fashion, significantly decreasing them in BJ cells, while stimulating their expression in T47D cells. Reduction in the expression of SASP factors and stress-related genes in BJ cells suggests that WEW acts as a protective factor, thereby reducing oxidative stress in normal cells, while making cancer cells more sensitive to the effects of cellular stress, thus increasing their elimination and consequently reducing their deleterious effects. 

“In conclusion, we have shown here that the new technology developed by Weo, WEW, could attenuate the overall process of cellular senescence in both normal BJ fibroblasts and cancer T47D cells.”

DOI - https://doi.org/10.18632/aging.205789

Corresponding authors - Brenda L. Court-Vazquez - bco@we-o.com, and Pierre-Yves Desprez - pydesprez@cpmcri.org

Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts

Keywords - aging, cellular senescence, senescence-associated secretory phenotype, oxidative stress, lung fibroblasts, breast cancer cells, senomorphic

About Aging-US

Aging publishes research papers in all fields of aging research, including but not limited to aging processes (from yeast to mammals), cellular senescence, age-related diseases (such as cancer and Alzheimer’s disease) and their prevention and treatment, anti-aging strategies and drug development, and, importantly, the role of signal transduction pathways in aging (such as mTOR) and potential approaches to modulate these signaling pathways to extend lifespan.

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

Modulation of Senescence Features Using Weo Electrolyzed Water

Upon diagnosing acute myeloid leukemia (AML), the initial step involves assessing a patient’s eligibility for intensive chemotherapy. The standard treatment protocol for newly diagnosed AML encompasses intensive chemotherapy to achieve complete remission, followed by post-remission therapy, which may include additional chemotherapy and/or stem cell transplantation. Complete response rates to this approach range from 60% to 85% in adults aged 60 or younger.

While this approach has proven effective, the risk of relapse within three years of diagnosis remains a significant concern. Numerous factors contribute to the likelihood of relapse, including short duration of remission, genetic derangements, prior allogeneic transplantation, advanced age, and concomitant comorbidities. These negative prognostic factors underscore the need for continuous exploration of novel therapeutic agents, as relapse remains a formidable barrier to treatment success.

In a new study, researchers Simonetta I. Gaumond, Rama Abdin, Joel Costoya, Andrew V. Schally (awarded the Nobel Prize in Physiology or Medicine in 1977), and Joaquin J. Jimenez from the University of Miami, Florida Atlantic University and Veterans Affairs Medical Center, Miami, investigated newly emerging therapies targeting drug resistance in AML. On April 8, 2024, their new research paper was published in Oncotarget’s Volume 15, entitled, “Exploring the role of GHRH antagonist MIA-602 in overcoming Doxorubicin-resistance in acute myeloid leukemia.”

Full blog - https://www.oncotarget.org/2024/05/23/combating-doxorubicin-resistant-acute-myeloid-leukemia/

Paper DOI - https://doi.org/10.18632/oncotarget.28579

Correspondence to - Simonetta I. Gaumond - sxg1204@miami.edu

Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28579

Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/

Keywords - cancer, leukemia, AML, resistance, growth hormone-releasing hormone, MIA-602

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

Facebook - https://www.facebook.com/Oncotarget/
X - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
YouTube - https://www.youtube.com/@OncotargetJournal
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/
Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh

MEDIA@IMPACTJOURNALS.COM

Combating Doxorubicin-Resistant Acute Myeloid Leukemia

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.

Read about the Aging (Aging-US) Scientific Integrity Process: https://aging-us.com/scientific-integrity

Effects of Zoledronic Acid on Senescence and SASP Markers

Aging (Aging-US) Podcast

Related tracks