Review
Biochemistry & Molecular Biology
Fabian Schmitt, Gunter P. Eckert
Summary: The study of aging is an important topic, and choosing the right model is crucial. The nematode C. elegans is a well-established model in aging research and has significant advantages in studying bioenergetics and secondary plant metabolites.
Article
Biochemistry & Molecular Biology
Ava Handley, Qiuli Wu, Tessa Sherry, Rebecca Cornell, Roger Pocock
Summary: This study reveals that excess dietary glucose leads to reduced insulin-1 expression in the BAG glutamatergic sensory neurons in C. elegans. The transcription factor ETS-5 directly controls the expression of INS-1 in these neurons and is down-regulated by glucose. Furthermore, INS-1 acts exclusively through the BAG neurons to inhibit fat storage via the insulin-like receptor DAF-2.
Article
Nutrition & Dietetics
Nkwachukwu Oziamara Okoro, Arome Solomon Odiba, Qi Yu, Bin He, Guiyan Liao, Cheng Jin, Wenxia Fang, Bin Wang
Summary: Dendrobium officinale, a widely used medicinal herb, has gained attention for its polysaccharide content and its potential medicinal properties. In this study, the anti-aging potential of polysaccharides extracted from D. officinale grown in different environments was investigated using Caenorhabditis elegans as a model. The findings showed that greenhouse-grown D. officinale polysaccharides had the optimal effect of extending lifespan and enhancing stress resistance. These results provide valuable information for the cultivation and medicinal applications of D. officinale.
Article
Pharmacology & Pharmacy
Junli Ma, Zekun Liu, Xinxin Gao, Yiyang Bao, Ying Hong, Xiaofang He, Weize Zhu, Yan Li, Wenjin Huang, Ningning Zheng, Lili Sheng, Ben Zhou, Hongzhuan Chen, Houkai Li
Summary: Accumulating evidence suggests that gut microbiota plays a role in aging-related disorders, but the mechanism of gut dysbiosis-related changes during aging is still unclear. In this study, gut microbiota remodeling through fecal microbiota transplantation (FMT) improved aging-related disorders in old mice, particularly protecting the liver and improving glucose sensitivity, inflammation, antioxidant capacity, and intestinal barrier. FMT increased the abundance of A.muciniphila and supplementation with A.muciniphila had similar benefits. Acetic acid, a short chain fatty acid, was consistently reversed by FMT and intervention with acetic acid had beneficial effects on both C. elegans and aging mice. Overall, this study demonstrated that gut microbiota remodeling improved aging-related disorders through A.muciniphila and its derived acetic acid, suggesting it as a potential strategy for healthy aging.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Nutrition & Dietetics
Xinlu Guo, Junjie Luo, Jingyi Qi, Xiya Zhao, Peng An, Yongting Luo, Guisheng Wang
Summary: The increasing elderly proportion of the population poses burdens on society, the economy, and the medical field. Polysaccharides have gained attention for their potential use in anti-aging therapies due to their natural and efficient biological properties, including antioxidant, anti-inflammatory, and immune regulatory activities.
Article
Environmental Sciences
Pei -Ling Yen, Cai-Ru Yang, Mei-Lun Huang, Ting -An Lin, Vivian Hsiu-Chuan Liao
Summary: This study aims to evaluate the effects of chronic DEHP exposure on innate immunosenescence in C. elegans. The length of the exposure period significantly impacts DEHP-induced age-related declines, which is linked to immunosenescence and oxidative stress. DEHP exposure increases the expression of riok-1, a human RIO kinase homolog, which is associated with DEHP-induced HLH-30/TFEB translocation.
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2023)
Article
Biochemical Research Methods
Jiunn-Liang Lin, Wei-Liang Kuo, Yi-Hao Huang, Tai-Lang Jong, Ao-Lin Hsu, Wen-Hsing Hsu
Summary: Caenorhabditis elegans is a popular model for aging studies due to its short lifespan. Methods for measuring the physiological age of C. elegans are needed for antiaging drug screening. With image processing and convolution neural networks, the physiological age of C. elegans can be measured with an average testing MAE of 1.58 days.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2021)
Article
Environmental Sciences
Chi-Wei Huang, Wan-Ru Liao, Chun Ming How, Pei-Ling Yen, Chia-Cheng Wei
Summary: The study found that ZEN significantly decreased locomotive behaviors in C. elegans. Lifespan and aging markers were also adversely affected by ZEN, which increased ROS levels and downregulated antioxidant genes. Long-term exposure to ZEN induced aging-related decline in C. elegans, associated with oxidative stress and inhibition of antioxidant defense.
ENVIRONMENTAL POLLUTION
(2021)
Article
Biology
Xinwei Yu, Matthew S. Creamer, Francesco Randi, Anuj K. Sharma, Scott W. Linderman, Andrew M. Leifer
Summary: A method called fDNC, based on the transformer network architecture, is proposed for automated tracking and identifying neurons in C. elegans. This method predicts neural correspondence quickly without requiring straightening or transforming the animal into a canonical coordinate system, making it suitable for future real-time applications.
Article
Pharmacology & Pharmacy
Na Li, Xi Li, Yan-Ling Shi, Jian-Mei Gao, Yu-Qi He, Fei Li, Jing-Shan Shi, Qi-Hai Gong
Summary: The study showed that TLB had beneficial effects on C. elegans, significantly reducing ROS and MDA levels while increasing antioxidant enzyme activities. TLB's anti-oxidative effects were mediated by the SKN1/SIRT3/DAF16 signaling pathway, contributing to the prolonged lifespan of C. elegans.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Zhimin Qi, Huihui Ji, Monika Le, Hanmei Li, Angela Wieland, Sonja Bauer, Li Liu, Michael Wink, Ingrid Herr
Summary: Sulforaphane extends the lifespan of C. elegans by modulating the insulin/IGF-1 signaling pathway, promoting healthspan by increasing mobility and appetite while reducing lipofuscin accumulation.
Article
Pharmacology & Pharmacy
Ganlan Zhang, Hui Liu, Ting Xue, Xiangming Kong, Dongmei Tian, Libo Luo, Yanhua Yang, Keqing Xu, Youheng Wei, Ziheng Zhuang
Summary: Aging is a process of degenerative changes that cause diseases and disabilities. Research aims to find drugs that can extend lifespan and treat age-related diseases. Ribavirin has been discovered as a potential drug for aging intervention by inhibiting TOR signaling and activating AMPK. Its anti-aging effect is mediated via AMPK-TOR signaling.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lei Zhou, Jin Liu, Lan-Lan Bu, Duan-Fang Liao, Shao-Wu Cheng, Xi-Long Zheng
Summary: The novel compound curcumin acetylsalicylate (CA) was found to extend the lifespan of Caenorhabditis elegans in a dose-dependent manner, decrease oxidative stress, and increase the expression of antioxidative genes. Activation of the DAF-16 transcription factor by CA may contribute to delaying aging in C. elegans.
Article
Biochemistry & Molecular Biology
Morgan Taylor, Olivia Marx, Adam Norris
Summary: Gene expression is a complex process that involves regulatory layers and their interactions. By conducting a reverse-genetic interaction screen in C. elegans, we discovered strong genetic interactions between ALS-related RBPs (fust-1 and tdp-1) and the homeodomain TF ceh-14, which resulted in fertility defects. Our RNA-Seq analysis revealed that ceh-14 controls transcript levels while fust-1 and tdp-1 have a shared role in exon inhibition, and skipping a specific exon rescued the fertility defects in the double mutants.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Kerry C. Ryan, Zahra Ashkavand, Shaarika Sarasija, Jocelyn T. Laboy, Rohan Samarakoon, Kenneth R. Norman
Summary: Metabolic dysfunction and protein aggregation are common characteristics in age-related neurodegenerative diseases. Mutations in presenilin genes can lead to familial Alzheimer's disease, while loss of SEL-12/presenilin results in hyperactivation of the mTORC1 pathway. This hyperactivation exacerbates proteostasis defects and neuronal dysfunction in sel-12 mutants, highlighting the critical role of presenilin in promoting neuronal health.
Article
Biology
Holly E. Kinser, Matthew C. Mosley, Isaac B. Plutzer, Zachary Pincus
Summary: The study found that individual lifespan variability is high within populations across species and suggested that differences in expression of key regulatory genes are driving factors. Testing showed that gene expression can effectively predict future lifespan, with long-lived and short-lived individuals exhibiting divergent patterns of transgene expression and transcriptional regulation. Additionally, a hierarchy of redundancy in lifespan-predictive ability among different transgenes expressed in distinct tissues was demonstrated.
Review
Oncology
Vida Karimnia, Frank J. Slack, Jonathan P. Celli
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with current clinical trials showing limited improvements in patient survival. Photodynamic therapy (PDT) has emerged as a potential approach for treating pancreatic tumors based on studies indicating its effectiveness in activating photosensitizing agents in target tissues.
Article
Oncology
Christos Miliotis, Frank J. Slack
Summary: In gastric cancer, miR-105-5p has been identified as a key regulator of PD-L1 expression, impacting T cell activation, and could serve as a potential biomarker and target for combination immunotherapy targeting PD-1/PD-L1 interactions.
Article
Multidisciplinary Sciences
Drew Benjamin Sinha, Zachary Scott Pincus
Summary: This study investigates the early-life changes in movement in C. elegans, and finds that movement declines as early as the first two days of adulthood, with high interindividual variability. These findings suggest that movement is a highly dynamic behavior early in life, and factors driving movement decline may begin acting as early as the first day of adulthood.
Article
Multidisciplinary Sciences
Jeffrey R. Haswell, Kaia Mattioli, Chiara Gerhardinger, Philipp G. Maass, Daniel J. Foster, Paola Peinado, Xiaofeng Wang, Pedro P. Medina, John L. Rinn, Frank J. Slack
Summary: This study describes a method to modulate lncRNA expression during human embryonic stem cell differentiation and identifies key lncRNA loci involved in differentiation. A clustering approach was developed to infer mechanisms of action of lncRNA hits, leading to the validation of FOXD3-AS1 as a functional lncRNA essential for pluripotency and differentiation. The cell lines and methodology presented in this study can be adapted to discover and characterize novel regulators of differentiation into any lineage.
Article
Oncology
Allison R. Baker, Christos Miliotis, Julia Ramirez-Moya, Talia Marc, Ioannis S. Vlachos, Pilar Santisteban, Frank J. Slack
Summary: ADAR1 plays a critical role in triple-negative breast cancer, and its loss leads to reduced cell growth, invasion, and mammosphere formation. ADAR1 regulates both coding and noncoding targets by altering gene expression level, A-to-I editing, and splicing. The study also reveals that several tumor suppressor miRNAs are upregulated upon ADAR1 loss, suppressing cell-cycle progression and invasion.
MOLECULAR CANCER RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Wen Cai Zhang, Nicholas Skiados, Fareesa Aftab, Cerena Moreno, Luis Silva, Paul Joshua Anthony Corbilla, John M. Asara, Aaron N. Hata, Frank J. Slack
Summary: In EGFR-mutant lung cancer, drug-tolerant persister cells (DTPCs) show prolonged survival when receiving EGFR tyrosine kinase inhibitor (TKI) treatments. They are a likely source of drug resistance. This study found that upregulation of miR-21-5p and miR-21-3p tune purine metabolism leading to increased drug tolerance.
CANCER GENE THERAPY
(2022)
Correction
Biotechnology & Applied Microbiology
Wen Cai Zhang, Nicholas Skiados, Fareesa Aftab, Cerena Moreno, Luis Silva, Paul Joshua Anthony Corbilla, John M. Asara, Aaron N. Hata, Frank J. Slack
CANCER GENE THERAPY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Sai Pallavi Pradeep, Shipra Malik, Frank J. Slack, Raman Bahal
Summary: RNA therapeutics have become the next-generation therapy for many diseases, using Watson-Crick base-pairing rules to recognize and modulate target RNA. Antisense oligonucleotides (ASOs) are a powerful approach to treat genetic disorders by altering gene expression. PNAs, with their synthetic DNA mimic structure, have been explored as an effective and safe RNA-targeting platform, demonstrating advances in coding and noncoding RNA targeting for therapeutic applications.
Article
Biochemistry & Molecular Biology
Adrienne Vancura, Alejandro H. Gutierrez, Thorben Hennig, Carlos Pulido-Quetglas, Frank J. Slack, Rory Johnson, Simon Haefliger
Summary: This study has found a bias in the evaluation of evolutionary conservation for cancer-related lncRNAs, raising doubts about its relevance in cancer research.
Article
Cell Biology
Latika Matai, Thalyana Stathis, Jonathan D. Lee, Christine Parsons, Tanvi Saxena, Kovi Shlomchik, Frank J. Slack
Summary: Several microRNAs, such as miR-228 and miR-229-66, have been identified as regulators of aging pathways in C. elegans. These microRNAs interact with transcription factors and are required for normal lifespan and longevity. miR-229-66 is specifically involved in lifespan extension through dietary restriction, reduced insulin signaling, and SKN-1 activation.
Article
Oncology
Urmila Jagtap, Erik S. Anderson, Frank J. Slack
Summary: Circular RNAs (circRNA) have gained significant attention as new components of disease mechanisms and potential biomarkers in various diseases, including cancer. They are highly conserved and show specific expression patterns in different developmental stages and diseases. Numerous studies have identified circRNA expression patterns associated with specific cancer types and patient prognosis. This article provides an overview of registered clinical trials investigating the value of circRNAs as cancer biomarkers and discusses their potential in clinical cancer care. Overall, circRNAs are actively being studied as diagnostic, predictive, and prognostic biomarkers, and their potential as therapeutic targets support ongoing translational and clinical research.
Article
Biochemistry & Molecular Biology
Soo Mi Lee, Michael T. Winters, Ivan Martinez, Frank J. Slack
Summary: The Keystone Symposium 'Small Regulatory RNAs: From Bench to Bedside' focused on the biology and therapeutic applications of small regulatory RNAs. The conference aimed to facilitate the translation of research findings into clinical tools and foster collaboration between academia and industry. It provided a platform for scientists to present and discuss their research in the field of small regulatory RNAs.
Review
Biochemistry & Molecular Biology
Latika Matai, Frank J. Slack
Summary: Aging is associated with protein misfolding diseases and the failure to maintain proteostasis, due to the accumulation of damaged and misfolded proteins and weakened cellular stress response pathways. MiRNAs play important roles in controlling aging and regulating proteostasis and stress responses during aging and age-related diseases. This review focuses on the role of individual miRNAs in age-associated protein folding and degradation, as well as their relationships with organelle-specific stress response pathways.
Article
Cell Biology
Maria Mavrikaki, Jonathan D. Lee, Isaac H. Solomon, Frank J. Slack
Summary: COVID-19 infection is associated with brain aging and emphasizes the value of neurological follow-up in recovered individuals.
