Aging-US

BUFFALO, NY- February 27, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 3, entitled, “The anti-aging effect of vitamin D and vitamin D receptor in Drosophila midgut.”

Adult stem cells are pivotal for maintaining tissue homeostasis, and their functional decline is linked to aging and its associated diseases, influenced by the niche cells’ environment. Age- and cancer-related reduction of vitamin D and its receptor levels are well documented in human clinical studies. However, the mechanisms through which the vitamin D/vitamin D receptor (VitD/VDR) pathway contributes to anti-aging and extends life expectancy are not well understood. In this new study, researchers Joung-Sun Park, Hyun-Jin Na and Yung-Jin Kim from Pusan National University and Korea Food Research Institute aimed to determine the protective role of the vitamin D/vitamin D receptor pathway in differentiated enterocytes (ECs) during intestinal stem cell (ISC) aging.

“This study aimed to determine the protective role of VitD/VDR in differentiated ECs during ISC aging using the adult Drosophila intestine model.”

By utilizing a well-established Drosophila midgut model for stem cell aging biology, the researchers revealed that vitamin D receptor knockdown in ECs induced ISC proliferation, EC death, ISC aging, and enteroendocrine cell differentiation. Additionally, age- and oxidative stress-induced increases in ISC proliferation and centrosome amplification were reduced by vitamin D treatment. In conclusion, this study provides direct evidence of the anti-aging role of the VitD/VDR pathway, involving protecting ECs during aging, and provides valuable insights for exploring the molecular mechanisms underlying enhanced healthy aging in Drosophila.

“Our findings suggest a direct evidence of the anti-aging role of the vitamin D/vitamin D receptor pathway and provides insights into the molecular mechanisms underlying healthy aging in Drosophila.”

DOI - https://doi.org/10.18632/aging.205518

Corresponding author - Joung-Sun Park - [email protected]

Sign up for free Altmetric alerts about this article -

https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205518

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

Keywords - aging, Drosophila, vitamin D, vitamin D receptor, anti-aging, intestinal stem cell

About Aging-US

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

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

Facebook - https://www.facebook.com/AgingUS/

X - https://twitter.com/AgingJrnl

Instagram - https://www.instagram.com/agingjrnl/

YouTube - https://www.youtube.com/@AgingJournal

LinkedIn - https://www.linkedin.com/company/aging/

Pinterest - https://www.pinterest.com/AgingUS/

Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

Media Contact

18009220957

BUFFALO, NY- February 21, 2024 – A new #researchpaper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 3, entitled, “Disruption of mitochondrial unfolded protein response results in telomere shortening in mouse oocytes and somatic cells.”

Caseinolytic peptidase P (CLPP) plays a central role in mitochondrial unfolded protein response (mtUPR) by promoting the breakdown of misfolded proteins and setting in motion a cascade of reactions to re-establish protein homeostasis. Global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. Telomeres are tandem repeats of 5’-TTAGGG-3’ sequences found at the ends of the chromosomes. Telomeres are essential for maintaining chromosome stability during somatic cell division and their shortening is associated with cellular senescence and aging.

In this new study, researchers Mauro Cozzolino, Yagmur Ergun, Emma Ristori, Akanksha Garg, Gizem Imamoglu, and Emre Seli from Yale School of Medicine, IVIRMA Global Research Alliance and Imperial College London asked whether the infertility and ovarian aging phenotype caused by global germline deletion of Clpp is associated with somatic aging, and tested telomere length in tissues of young and aging mice.

“In this study, we asked whether the infertility and ovarian aging phenotype caused by global germline deletion of Clpp is associated with somatic aging, and tested telomere length in young and aging mice gametes, gonads and somatic tissues.”

The team found that impaired mtUPR caused by the lack of CLPP is associated with accelerated telomere shortening in both oocytes and somatic cells of aging mice. In addition, expression of several genes that maintain telomere integrity was decreased, and double-strand DNA breaks were increased in telomeric regions. Their results highlight how impaired mtUPR can affect telomere integrity and demonstrate a link between loss of mitochondrial protein hemostasis, infertility, and somatic aging.

“Our findings demonstrate how loss of mitochondrial protein homeostasis may accelerate telomere shortening in oocytes and somatic cells, and provide a link between reproductive and somatic aging.”

DOI - https://doi.org/10.18632/aging.205543

Corresponding author - Emre Seli - [email protected]

Sign up for free Altmetric alerts about this article -

https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205543

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

Keywords - aging, telomere length, Clpp, mitochondrial dysfunction, unfolded protein response

About Aging-US

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

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

Facebook - https://www.facebook.com/AgingUS/

X - https://twitter.com/AgingJrnl

Instagram - https://www.instagram.com/agingjrnl/

YouTube - https://www.youtube.com/@AgingJournal

LinkedIn - https://www.linkedin.com/company/aging/

Pinterest - https://www.pinterest.com/AgingUS/

Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

Media Contact

18009220957

BUFFALO, NY- February 20, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 3, entitled, “Defining the progeria phenome.”

Progeroid disorders are a heterogenous group of rare and complex hereditary syndromes presenting with pleiotropic phenotypes associated with normal aging. Due to the large variation in clinical presentation the diseases pose a diagnostic challenge for clinicians which consequently restricts medical research. In this new study, researchers Cecilie Worm, Maya Elena Ramirez Schambye, Garik V. Mkrtchyan, Alexander Veviorskiy, Anastasia Shneyderman, Ivan V. Ozerov, Alex Zhavoronkov, Daniela Bakula, and Morten Scheibye-Knudsen from the University of Copenhagen and Insilico Medicine aimed to accommodate this challenge by compiling a list of known progeroid syndromes and calculating the mean prevalence of their associated phenotypes, defining what they term the ‘progeria phenome’.

“In this study, we have utilized phenome explorations to define the phenotypes associated with progerias and to develop tools to diagnose patients and identify new progeroid syndromes.”

The data were used to train a support vector machine that is available at https://www.mitodb.com and able to classify progerias based on phenotypes. Furthermore, this allowed the researchers to investigate the correlation of progeroid syndromes and syndromes with various pathogenesis using hierarchical clustering algorithms and disease networks. They detected that ataxia-telangiectasia like disorder 2, spastic paraplegia 49 and Meier-Gorlin syndrome display strong association to progeroid syndromes, thereby implying that the syndromes are previously unrecognized progerias.

“In conclusion, our study has provided tools to evaluate the likelihood of a syndrome or patient being progeroid. This is a considerable step forward in our understanding of what constitutes a premature aging disorder and how to diagnose them.”

DOI - https://doi.org/10.18632/aging.205537

Corresponding author - Morten Scheibye-Knudsen - [email protected]

Sign up for free Altmetric alerts about this article -

https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205537

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

Keywords - aging, progeria, premature aging, phenome, clinical phenotype

About Aging-US

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

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

Facebook - https://www.facebook.com/AgingUS/

X - https://twitter.com/AgingJrnl

Instagram - https://www.instagram.com/agingjrnl/

YouTube - https://www.youtube.com/@AgingJournal

LinkedIn - https://www.linkedin.com/company/aging/

Pinterest - https://www.pinterest.com/AgingUS/

Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

Media Contact

18009220957

Crossref is a non-profit organization that logs and updates citations for scientific publications. Each month, Crossref identifies a list of the most popular Aging (Aging-US) papers based on the number of times a DOI is successfully resolved.

Below are Crossref’s Top 10 Aging DOIs in 2023.

10: Old-age-induced obesity reversed by a methionine-deficient diet or oral administration of recombinant methioninase-producing Escherichia coli in C57BL/6 mice

DOI: https://doi.org/10.18632/aging.204783

Authors: Yutaro Kubota, Qinghong Han, Jose Reynoso, Yusuke Aoki, Noriyuki Masaki, Koya Obara, Kazuyuki Hamada, Michael Bouvet, Takuya Tsunoda, and Robert M. Hoffman

9: Metformin use history and genome-wide DNA methylation profile: potential molecular mechanism for aging and longevity

DOI: https://doi.org/10.18632/aging.204498

Authors: Pedro S. Marra, Takehiko Yamanashi, Kaitlyn J. Crutchley, Nadia E. Wahba, Zoe-Ella M. Anderson, Manisha Modukuri, Gloria Chang, Tammy Tran, Masaaki Iwata, Hyunkeun Ryan Cho, and Gen Shinozaki

8: Age prediction from human blood plasma using proteomic and small RNA data: a comparative analysis

DOI: https://doi.org/10.18632/aging.204787

Authors: Jérôme Salignon, Omid R. Faridani, Tasso Miliotis, Georges E. Janssens, Ping Chen, Bader Zarrouki, Rickard Sandberg, Pia Davidsson, and Christian G. Riedel

7: Characterization of the HDAC/PI3K inhibitor CUDC-907 as a novel senolytic

DOI: https://doi.org/10.18632/aging.204616

Authors: Fares Al-Mansour, Abdullah Alraddadi, Buwei He, Anes Saleh, Marta Poblocka, Wael Alzahrani, Shaun Cowley, and Salvador Macip

6: Potential reversal of biological age in women following an 8-week methylation-supportive diet and lifestyle program: a case series

DOI: https://doi.org/10.18632/aging.204602

Authors: Kara N. Fitzgerald, Tish Campbell, Suzanne Makarem, and Romilly Hodges

5: Leukocyte telomere length, T cell composition and DNA methylation age

DOI: https://doi.org/10.18632/aging.101293

Authors: Brian H. Chen, Cara L. Carty, Masayuki Kimura, Jeremy D. Kark, Wei Chen, Shengxu Li, Tao Zhang, Charles Kooperberg, Daniel Levy, Themistocles Assimes, Devin Absher, Steve Horvath, Alexander P. Reiner, and Abraham Aviv

4: DNA methylation GrimAge strongly predicts lifespan and healthspan

DOI: https://doi.org/10.18632/aging.101684

Authors: Ake T. Lu, Austin Quach, James G. Wilson, Alex P. Reiner, Abraham Aviv, Kenneth Raj, Lifang Hou, Andrea A. Baccarelli, Yun Li, James D. Stewart, Eric A. Whitsel, Themistocles L. Assimes, Luigi Ferrucci, and Steve Horvath

3: Deep biomarkers of aging and longevity: from research to applications

DOI: https://doi.org/10.18632/aging.102475

Authors: Alex Zhavoronkov, Ricky Li, Candice Ma, and Polina Mamoshina

2: An epigenetic biomarker of aging for lifespan and healthspan

DOI: https://doi.org/10.18632/aging.101414

Authors: Morgan E. Levine, Ake T. Lu, Austin Quach, Brian H. Chen, Themistocles L. Assimes, Stefania Bandinelli, Lifang Hou, Andrea A. Baccarelli, James D. Stewart, Yun Li, Eric A. Whitsel, James G Wilson, Alex P Reiner, Abraham Aviv, Kurt Lohman, Yongmei Liu, Luigi Ferrucci, and Steve Horvath

1: Chemically induced reprogramming to reverse cellular aging

DOI: https://doi.org/10.18632/aging.204896

Authors: Jae-Hyun Yang, Christopher A. Petty, Thomas Dixon-McDougall, Maria Vina Lopez, Alexander Tyshkovskiy, Sun Maybury-Lewis, Xiao Tian, Nabilah Ibrahim, Zhili Chen, Patrick T. Griffin, Matthew Arnold, Jien Li, Oswaldo A. Martinez, Alexander Behn, Ryan Rogers-Hammond, Suzanne Angeli, Vadim N. Gladyshev, and David A. Sinclair

Aging is an open-access, traditional, peer-reviewed journal that has published high-impact papers in all fields of aging research since 2009. All papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

For media inquiries, please contact [email protected].

BUFFALO, NY- February 15, 2024 – A new #research paper was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 3, entitled, “GV1001 reduces neurodegeneration and prolongs lifespan in 3xTg-AD mouse model through anti-aging effects.”

GV1001, which mimics the activity of human telomerase reverse transcriptase, protects neural cells from amyloid beta (Aβ) toxicity and other stressors through extra-telomeric function, as noted in our prior in vitro studies. As per a recent phase II clinical trial, it improves cognitive function in patients with moderate to severe dementia. However, the underlying protective mechanisms remain unclear.

In this new study, researchers Hyun-Hee Park, Hyuk Sung Kwon, Kyu-Yong Lee, Ye Eun Kim, Jeong-Woo Son, Na-Young Choi, Myung-Hoon Han, Dong Woo Park, Sangjae Kim, and Seong-Ho Koh from Hanyang University Guri Hospital, Hanyang University Graduate School of Biomedical Science and Engineering and Teloid Inc. aimed to investigate the effects of GV1001 on neurodegeneration, senescence, and survival in triple transgenic Alzheimer’s disease (AD) (3xTg-AD) mice.

“ [...] we hypothesised that GV1001 might have anti-aging effects and improve neurodegeneration and senescence in vivo as a possible mechanism for its beneficial effects on AD.”

GV1001 (1 mg/kg) was subcutaneously injected into old 3xTg-AD mice thrice a week until the endpoint for sacrifice, and survival was analysed. Magnetic resonance imaging (MRI) and Prussian blue staining (PBS) were performed to evaluate entry of GV1001 entrance into the brain. Diverse molecular studies were performed to investigate the effect of GV1001 on neurodegeneration and cellular senescence in AD model mice, with a particular focus on BACE, amyloid beta1-42 (Aβ1-42), phosphorylated tau, volume of dentate gyrus, β-galactosidase positive cells, telomere length, telomerase activity, and ageing-associated proteins.

GV1001 crossed the blood-brain barrier, as confirmed by assessing the status of ferrocenecarboxylic acid-conjugated GV1001 using magnetic resonance imaging and PBS. GV1001 increased the survival of 3xTg-AD mice. It decreased BACE and Aβ1-42 levels, neurodegeneration (i.e., reduced CA1, CA3 and dentate gyrus volume, decreased levels of senescence-associated β-galactosidase positive cells, and increased telomere length and telomerase activity), and levels of ageing-associated proteins.

“We suggest that GV1001 exerts anti-ageing effects in 3xTg-AD mice by reducing neurodegeneration and senescence, which contributes to improved survival.”

DOI - https://doi.org/10.18632/aging.205489

Corresponding authors - Sangjae Kim - [email protected], and Seong-Ho Koh - [email protected]

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

About Aging-US

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

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

Facebook - https://www.facebook.com/AgingUS/

X - https://twitter.com/AgingJrnl

Instagram - https://www.instagram.com/agingjrnl/

YouTube - https://www.youtube.com/@AgingJournal

LinkedIn - https://www.linkedin.com/company/aging/

Pinterest - https://www.pinterest.com/AgingUS/

Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

BUFFALO, NY- February 13, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 2, entitled, “IL-17 promotes IL-18 production via the MEK/ERK/miR-4492 axis in osteoarthritis synovial fibroblasts.”

The concept of osteoarthritis (OA) as a low-grade inflammatory joint disorder has been widely accepted. Many inflammatory mediators are implicated in the pathogenesis of OA. Interleukin (IL)-18 is a pleiotropic cytokine with versatile cellular functions that are pathogenetically important in immune responses, as well as autoimmune, inflammatory, and infectious diseases. IL-17, a proinflammatory cytokine mainly secreted by Th17 cells, is upregulated in OA patients. However, the role of IL-17 in OA progression is unclear.

In this new study, researchers Kun-Tsan Lee, Chih-Yang Lin, Shan-Chi Liu, Xiu-Yuan He, Chun-Hao Tsai, Chih-Yuan Ko, Yuan-Hsin Tsai, Chia-Chia Chao, Po-Chun Chen, and Chih-Hsin Tang from National Chung-Hsing University, Taichung Veterans General Hospital, Shin-Kong Wu Ho-Su Memorial Hospital, Mackay Medical College, China Medical University, Show-Chwan Memorial Hospital, Fu-Jen Catholic University, National Taiwan Normal University, Asia University, and China Medical University Hsinchu Hospital used synovial tissues collected from healthy donors and OA patients to detect the expression level of IL-18 by immunohistochemistry stain.

“Elucidation of the molecular mechanisms and main factors involved in OA pathogenesis may help with the development of novel therapeutic targets that relieve OA pain or prevent the disease from progressing.”

The OA synovial fibroblasts (OASFs) were incubated with recombinant IL-17 and subjected to Western blot, qPCR, and ELISA to examine IL-18 expression level. The chemical inhibitors and siRNAs which targeted signal pathways were used to investigate signal pathways involved in IL-17-induced IL-18 expression. The microRNAs which participated IL-18 expression were surveyed with online databases miRWalk and miRDB, followed by validation with qPCR.

This study revealed significantly higher levels of IL-18 expression in synovial tissue from OA patients compared with healthy controls, as well as increased IL-18 expression in OASFs from rats with severe OA. In vitro findings indicated that IL-17 dose-dependently promoted IL-18 production in OASFs. Molecular investigations revealed that the MEK/ERK/miR-4492 axis stimulated IL-18 production when OASFs were treated with IL-17.

“This study provides novel insights into the role of IL-17 in the pathogenesis of OA, which may help to inform OA treatment in the future.”

DOI - https://doi.org/10.18632/aging.205462

Corresponding authors - Po-Chun Chen - [email protected], and Chih-Hsin Tang - [email protected]

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

About Aging-US

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

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

Facebook - https://www.facebook.com/AgingUS/

X - https://twitter.com/AgingJrnl

Instagram - https://www.instagram.com/agingjrnl/

YouTube - https://www.youtube.com/@AgingJournal

LinkedIn - https://www.linkedin.com/company/aging/

Pinterest - https://www.pinterest.com/AgingUS/

Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

Media Contact

18009220957

BUFFALO, NY- February 7, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 2, entitled, “PROX1 interaction with α-SMA-rich cancer-associated fibroblasts facilitates colorectal cancer progression and correlates with poor clinical outcomes and therapeutic resistance.”

The tumor microenvironment (TME) plays a vital role in tumor progression through intricate molecular interactions. Cancer-associated fibroblasts (CAFs), notably those expressing alpha-smooth muscle actin (α-SMA) or myofibroblasts, are instrumental in this context and correlate with unfavorable outcomes in colorectal cancer (CRC). While several transcription factors influence TME, the exact regulator causing CAF dysregulation in CRC remains elusive. Prospero Homeobox 1 (PROX1) stands out, as its inhibition reduces α-SMA-rich CAF activity. However, the therapeutic role of PROX1 is debated due to inconsistent study findings.

In this new study, researchers Shiue-Wei Lai, Yi-Chiao Cheng, Kee-Thai Kiu, Min-Hsuan Yen, Ying-Wei Chen, Vijesh Kumar Yadav, Chi-Tai Yeh, Kuang-Tai Kuo, and Tung-Cheng Chang from Taipei’s National Defense Medical Center, Taipei Medical University, Taipei Medical University Shuang-Ho Hospital, and National Taitung University used the ULCAN portal and noted an elevated PROX1 level in advanced colon adenocarcinoma, linking to a poor prognosis. Their assays determined the impact of PROX1 overexpression on CRC cell properties, while co-culture experiments spotlighted the PROX1-CAF relationship. Molecular expressions were validated by qRT-PCR and Western blots, with in vivo studies further solidifying the observations.

“Our study emphasized the connection between PROX1 and α-SMA in CAFs.”

Elevated PROX1 in CRC samples correlated with increased α-SMA in tumors. PROX1 modulation influenced the behavior of specific CRC cells, with its overexpression fostering invasiveness. Kaplan-Meier evaluations demonstrated a link between PROX1 or α-SMA and survival outcomes. Consequently, PROX1, alone or with α-SMA, emerges as a CRC prognostic marker. Co-culture and animal experiments further highlighted this relationship.

PROX1 appears crucial in modulating CRC behavior and therapeutic resistance within the TME by influencing CAFs, signifying the combined PROX1/α-SMA gene as a potential CRC prognostic marker. The concept of developing inhibitors targeting this gene set emerges as a prospective therapeutic strategy. However, this study is bound by limitations, including potential challenges in clinical translation, a focused exploration on PROX1/α-SMA potentially overlooking other significant molecular contributors, and the preliminary nature of the inhibitor development proposition.

“As we advance in this field, the development and clinical validation of small-molecule inhibitors targeting PROX1/α-SMA become imperative, paving the way to refine and optimize CRC therapeutic interventions.”

DOI - https://doi.org/10.18632/aging.205447

Corresponding author - Tung-Cheng Chang - [email protected]

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​​.

BUFFALO, NY- February 6, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 2, entitled, “Epigenetic drift underlies epigenetic clock signals, but displays distinct responses to lifespan interventions, development, and cellular dedifferentiation.”

Changes in DNA methylation with age are observed across the tree of life. The stereotypical nature of these changes can be modeled to produce epigenetic clocks capable of predicting chronological age with unprecedented accuracy. Despite the predictive ability of epigenetic clocks and their utility as biomarkers in clinical applications, the underlying processes that produce clock signals are not fully resolved, which limits their interpretability.

In this new study, researchers Emily M. Bertucci-Richter, Ethan P. Shealy, and Benjamin B. Parrott from the University of Georgia developed a computational approach to spatially resolve the within read variability or “disorder” in DNA methylation patterns and test if age-associated changes in DNA methylation disorder underlie signals comprising epigenetic clocks.

“Herein, we apply novel read-based strategies to resolve age-associated epigenetic disorder across the mouse genome.”

The team found that epigenetic clock loci are enriched in regions that both accumulate and lose disorder with age, suggesting a link between DNA methylation disorder and epigenetic clocks. They then developed epigenetic clocks that are based on regional disorder of DNA methylation patterns and compare their performance to other epigenetic clocks by investigating the influences of development, lifespan interventions, and cellular dedifferentiation. The researchers identified common responses as well as critical differences between canonical epigenetic clocks and those based on regional disorder, demonstrating a fundamental decoupling of epigenetic aging processes.

“Collectively, we identify key linkages between epigenetic disorder and epigenetic clocks and demonstrate the multifaceted nature of epigenetic aging in which stochastic processes occurring at non-random loci produce predictable outcomes.”

DOI - https://doi.org/10.18632/aging.205503

Corresponding author - Emily M. Bertucci-Richter - [email protected]

Sign up for free Altmetric alerts about this article -

https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205503

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

Keywords - aging, epigenetic aging, epigenetic drift, epigenetic rejuvenation, lifespan, DNA methylation

About Aging-US

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

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

Facebook - https://www.facebook.com/AgingUS/

X - https://twitter.com/AgingJrnl

Instagram - https://www.instagram.com/agingjrnl/

YouTube - https://www.youtube.com/@AgingJournal

LinkedIn - https://www.linkedin.com/company/aging/

Pinterest - https://www.pinterest.com/AgingUS/

Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

Media Contact

18009220957

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and heterogeneous form of cancer that affects thousands of individuals worldwide. The prognosis for HNSCC patients can vary greatly, depending on factors such as tumor stage and site. The tumor microenvironment (TME) plays a crucial role in tumorigenesis and disease progression, with cellular senescence being a key component. Senescent cells, characterized by cell-cycle arrest, have been shown to have both tumor-suppressive and tumor-promoting effects. However, the prognostic significance of senescence-related TME genes in HNSCC remains poorly understood.

In a new study, researchers Young Chan Lee, Yonghyun Nam, Minjeong Kim, Su Il Kim, Jung-Woo Lee, Young-Gyu Eun, and Dokyoon Kim from Kyung Hee University, Kyung Hee University Hospital at Gangdong, and the University of Pennsylvania aimed to investigate the prognostic significance of senescence-related TME genes in HNSCC and their potential implications for immunotherapy response. They utilized data from The Cancer Genome Atlas (TCGA) to identify two distinct subtypes of HNSCC based on the expression of senescence-related TME genes. The team then constructed a risk model consisting of senescence-related TME core genes (STCGs) and validated its prognostic capability in independent cohorts. Their research paper was chosen as an Aging cover paper and published in Volume 16, Issue 2, entitled, “Prognostic significance of senescence-related tumor microenvironment genes in head and neck squamous cell carcinoma.”

Full blog - https://aging-us.org/2024/02/senescence-related-tme-genes-as-key-prognostic-predictors-in-hnscc/

Paper DOI - https://doi.org/10.18632/aging.205346

Corresponding authors - Young-Gyu Eun - [email protected], and Dokyoon Kim - [email protected]

Sign up for free Altmetric alerts about this article -

https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205346

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

Keywords - aging, cellular senescence, head and neck cancer, immunotherapy, microenvironment, single cell

About Aging-US

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

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

Facebook - https://www.facebook.com/AgingUS/

X - https://twitter.com/AgingJrnl

Instagram - https://www.instagram.com/agingjrnl/

YouTube - https://www.youtube.com/@AgingJournal

LinkedIn - https://www.linkedin.com/company/aging/

Pinterest - https://www.pinterest.com/AgingUS/

Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

Media Contact

18009220957

BUFFALO, NY- January 31, 2024 – A new #research paper was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 2, entitled, “Prognostic significance of senescence-related tumor microenvironment genes in head and neck squamous cell carcinoma.”

The impact of the senescence related microenvironment on cancer prognosis and therapeutic response remains poorly understood. In this new study, researchers Young Chan Lee, Yonghyun Nam, Minjeong Kim, Su Il Kim, Jung-Woo Lee, Young-Gyu Eun, and Dokyoon Kim from Kyung Hee University, Kyung Hee University Hospital at Gangdong, and the University of Pennsylvania investigated the prognostic significance of senescence related tumor microenvironment genes (PSTGs) and their potential implications for immunotherapy response.

Using the Cancer Genome Atlas- head and neck squamous cell carcinoma (HNSC) data, the researchers identified two subtypes based on the expression of PSTGs, acquired from tumor-associated senescence genes, tumor microenvironment (TME)-related genes, and immune-related genes, using consensus clustering. Using the LASSO, they constructed a risk model consisting of senescence related TME core genes (STCGs). The two subtypes exhibited significant differences in prognosis, genetic alterations, methylation patterns, and enriched pathways, and immune infiltration.

“Our risk model stratified patients into high-risk and low-risk groups and validated in independent cohorts.”

The high-risk group showed poorer prognosis and immune inactivation, suggesting reduced responsiveness to immunotherapy. Additionally, the team observed a significant enrichment of STCGs in stromal cells using single-cell RNA transcriptome data. Their findings highlight the importance of the senescence related TME in HNSC prognosis and response to immunotherapy.

“This study contributes to a deeper understanding of the complex interplay between senescence and the TME, with potential implications for precision medicine and personalized treatment approaches in HNSC.”

DOI - https://doi.org/10.18632/aging.205346

Corresponding authors - Young-Gyu Eun - [email protected], and Dokyoon Kim - [email protected]

Sign up for free Altmetric alerts about this article -

https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205346

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

Keywords - aging, cellular senescence, head and neck cancer, immunotherapy, microenvironment, single cell

About Aging-US

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

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

Facebook - https://www.facebook.com/AgingUS/

X - https://twitter.com/AgingJrnl

Instagram - https://www.instagram.com/agingjrnl/

YouTube - https://www.youtube.com/@AgingJournal

LinkedIn - https://www.linkedin.com/company/aging/

Pinterest - https://www.pinterest.com/AgingUS/

Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

Media Contact

18009220957