Review
Cell Biology
Agata Tyczewska, Alicja Rzepczak, Daria Sobanska, Kamilla Grzywacz
Summary: Aging is a gradual decline of various functions of organisms resulting in diminished abilities to protect against environmental damage and reinforce physiological harmony. Recent studies have shown that the mechanisms of lifespan regulation are conserved throughout evolution. This review focuses on the emerging roles of tRNA-associated processes in aging and lifespan regulation, including tRNA metabolism, epitranscriptome, and tRNA-derived fragments. Understanding the basic mechanisms of aging could lead to the development of new diagnostics and treatments for aging-related diseases.
AGEING RESEARCH REVIEWS
(2023)
Review
Nutrition & Dietetics
Diogo Carregosa, Sara Mota, Sofia Ferreira, Beatriz Alves-Dias, Natasa Loncarevic-Vasiljkovic, Carolina Lage Crespo, Regina Menezes, Rita Teodoro, Claudia Nunes dos Santos
Summary: The rise of neurodegenerative diseases in an aging population poses significant health, social, and economic consequences. Diets rich in (poly)phenols have been shown to have health benefits in preventing cognitive decline and neurodegenerative diseases. The role of gut microbiota in metabolizing (poly)phenols and the potential brain effects of low molecular weight (poly)phenol metabolites still require further research.
Review
Cell Biology
Anja Wagner, Markus Schosserer
Summary: RNA modifications play a regulatory role in gene expression, but the underlying molecular mechanisms and physiological consequences are still poorly understood. This review systematically examines different types of RNA modifications, analysis methods, challenges in the field, and associations with human diseases. Furthermore, evidence is compiled for the connection between RNA modification enzymes and lifespan in yeast, worms, and flies.
AGEING RESEARCH REVIEWS
(2022)
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
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)
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
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
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
Biology
Manish Pandey, Sakshi Bansal, Sudipta Bar, Amit Kumar Yadav, Nicholas S. Sokol, Jason M. Tennessen, Pankaj Kapahi, Geetanjali Chawla
Summary: In fruit flies, two neuronally enriched and highly conserved microRNAs, miR-125 and let-7, have been shown to mediate the response to dietary restriction (DR) that extends lifespan. MiR-125 functions in neurons, while its target gene chinmo modulates fat metabolism and longevity in both neurons and the fat body. Chinmo exerts its DR effects by regulating the expression of several proteins, indicating a potential avenue for miR-125 and its downstream effectors as drug candidates for late-onset diseases and biomarkers for healthy aging in humans.
Editorial Material
Biochemistry & Molecular Biology
Patrick J. Hu
Summary: The study in C. elegans model showed that a conserved insulin-like signaling pathway plays an important role in shaping the phylogenetic composition of the gut microbiome.
Article
Cell Biology
David H. Meyer, Bjoern Schumacher
Summary: Aging clocks separate biological age from chronological age, with recent research showing that methylation markers can estimate biological age accurately. A new approach using temporal scaling and binarization of C. elegans transcriptomes has been developed to predict biological age, showing potential for wide application in genetic, nutritional, environmental, and therapeutic interventions in the aging process.
Editorial Material
Biochemistry & Molecular Biology
Erin J. Cram
Summary: Cells release extracellular vesicles containing proteins, lipids, and RNAs to communicate with other cells and remove damaged components. In C. elegans, neuronal cells release large extracellular vesicles called exophers to clear damaged organelles and protein aggregates. Researchers have now shown that embryos in the uterus can stimulate body wall muscle cells to release exophers loaded with yolk, which are then absorbed by oocytes to nourish the next generation of embryos.
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
Anatomy & Morphology
Jil Messerer, Christoph Wrede, Julia Schipke, Christina Brandenberger, Mahmoud Abdellatif, Tobias Eisenberg, Frank Madeo, Simon Sedej, Christian Muhlfeld
Summary: Aging is associated with dysfunctional mitochondria, and spermidine treatment can normalize the number and morphology of mitochondria in aged hearts.
JOURNAL OF ANATOMY
(2023)
Review
Immunology
Lucillia Bezu, Oliver Kepp, Guido Kroemer
Summary: Intratumoral injection of oncolytic agents or local administration of non-viral oncolytic therapies can activate an anticancer immune response, while local anesthetics injected into malignant lesions also possess antineoplastic effects. Combining local anesthetics with immune checkpoint inhibition can significantly improve overall survival. The molecular and cellular mechanisms underlying the combination therapy's efficacy are summarized.
SEMINARS IN IMMUNOPATHOLOGY
(2023)
Article
Cell Biology
Sol Beccari, Virginia Sierra-Torre, Jorge Valero, Marta Pereira-Iglesias, Mikel Garcia-Zaballa, Federico N. Soria, Laura De Las Heras-garcia, Alejandro Carretero-Guillen, Estibaliz Capetillo-Zarate, Maria Domercq, Paloma R. Huguet, David Ramonet, Ahmed Osman, Wei Han, Cecilia Dominguez, Travis E. Faust, Omar Touzani, Olatz Pampliega, Patricia Boya, Dorothy Schafer, Guillermo Marino, Emmanuelle Canet-Soulas, Klas Blomgren, Ainhoa Plaza-Zabala, Amanda Sierra
Summary: The dysfunction of microglial phagocytosis, resulting in impaired engulfment and degradation, is found in stroke and other brain disorders. This dysfunction is not explained by transcriptional changes but is related to energy depletion triggered by oxygen and nutrient deprivation. Modulating microglial autophagy may be a potential therapeutic strategy for stroke and other brain disorders.
Article
Cell Biology
Maria Castedo, Antoine Lafarge, Guido Kroemer
Summary: Deletion or inhibition of the PARP1 gene protects mice against cerebral ischemia and Parkinson's disease, while PARP1 inhibitors are used to eradicate vulnerable cancer cells. Excessive activation of PARP1 is involved in a specific cell death pathway called parthanatos, and inhibition of PARP1 in cancer cells amplifies DNA damage to a lethal level. Therefore, PARP1 plays a context-dependent role in cell fate decisions. Additionally, PARP1 appears to have an ambiguous role in organismal aging.
Review
Cell Biology
Lucille Ferret, Karla Alvarez-Valadez, Jennifer Riviere, Alexandra Muller, Natalia Bohalova, Luo Yu, Lionel Guittat, Vaclav Brazda, Guido Kroemer, Jean-Louis Mergny, Mojgan Djavaheri-Mergny
Summary: Guanine-quadruplex structures (G4) are formed by guanine-rich DNA and RNA sequences and control gene expression mechanisms. G4 ligands have been developed for potential therapeutic applications in human diseases. Recent evidence suggests that G4 ligands may target cellular components such as lysosomes and mitochondria.
Review
Cardiac & Cardiovascular Systems
Mahmoud Abdellatif, Peter P. Rainer, Simon Sedej, Guido Kroemer
Summary: In this Review, Kroemer and colleagues summarize eight molecular hallmarks of cardiovascular ageing, including disabled macroautophagy, loss of proteostasis, genomic instability, epigenetic alterations, mitochondrial dysfunction, cell senescence, dysregulated neurohormonal signalling and inflammation. Targeting these hallmarks therapeutically can attenuate residual cardiovascular risk in older individuals.
NATURE REVIEWS CARDIOLOGY
(2023)
Article
Multidisciplinary Sciences
Luis Filipe Costa-Machado, Esther Garcia-Dominguez, Rebecca L. McIntyre, Jose Luis Lopez-Aceituno, Alvaro Ballesteros-Gonzalez, Andrea Tapia-Gonzalez, David Fabregat-Safont, Tobias Eisenberg, Jesus Gomez, Adrian Plaza, Aranzazu Sierra-Ramirez, Manuel Perez, David Villanueva-Bermejo, Tiziana Fornari, Maria Isabel Loza, Gonzalo Herradon, Sebastian J. Hofer, Christoph Magnes, Frank Madeo, Janet S. Duerr, Oscar J. Pozo, Maximo-Ibo Galindo, Isabel del Pino, Riekelt H. Houtkooper, Diego Megias, Jose Vina, Mari Carmen Gomez-Cabrera, Pablo J. Fernandez-Marcos
Summary: Reversible mitochondrial stress, known as mitohormesis, improves mitochondrial function and delays aging. In this study, harmol, a beta-carboline compound, was found to induce mitohormesis in peripheral organs, alleviate aging-related phenotypes in mice, and extend lifespan in invertebrate models.
NATURE COMMUNICATIONS
(2023)
Article
Nutrition & Dietetics
Julia Martin-Virgala, Sara Fernandez-Villabrille, Beatriz Martin-Carro, Isaac Tamargo-Gomez, Juan F. Navarro-Gonzalez, Carmen Mora-Fernandez, Laura Calleros, Elena Astudillo-Cortes, Noelia Avello-Llano, Guillermo Marino, Adriana S. Dusso, Cristina Alonso-Montes, Sara Panizo, Jorge B. Cannata-Andia, Manuel Naves-Diaz, Natalia Carrillo-Lopez
Summary: This study investigated the potential role of sKlotho as an early biomarker in Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD). The findings indicated that sKlotho is a reliable indicator of kidney alpha-Klotho and may protect against osteogenic differentiation by increasing autophagy. Further studies are needed to explore the mechanisms of this potential protective effect.
Article
Cell Biology
Yaiza Corral Nieto, Sokhna M. S. Yakhine-Diop, Paula Moreno-Cruz, Laura Manrique Garcia, Amanda Gabrielly Pereira, Jose A. Morales-Garcia, Mireia Niso-Santano, Rosa A. Gonzalez-Polo, Elisabet Uribe-Carretero, Sylvere Durand, Maria Chiara Maiuri, Marta Paredes-Barquero, Eva Alegre-Cortes, Saray Canales-Cortes, Adolfo Lopez de Munain, Jordi Perez-Tur, Ana Perez-Castillo, Guido Kroemer, Jose M. Fuentes, Jose M. Bravo-San Pedro
Summary: Using mass spectrometry, this study identified metabolic changes in the liver of mouse models of Parkinson's disease, with the aim of finding new peripheral biomarkers for diagnosis.
Review
Oncology
Andrew Maltez Thomas, Marine Fidelle, Bertrand Routy, Guido Kroemer, Jennifer A. Wargo, Nicola Segata, Laurence Zitvogel
Summary: Many studies have identified Gut OncoMicrobiome Signatures (GOMS) as biomarkers for predicting immune-checkpoint inhibitor (ICI) efficacy. There is an association between oncogenesis and intestinal dysbiosis, and GOMS are shared between patients with various cancer subtypes and individuals with chronic inflammatory disorders. This review discusses these patterns, presents findings from a meta-analysis of GOMS associated with clinical benefit from ICIs, and proposes practical guidelines for incorporating GOMS in decision-making in immuno-oncology.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Oliver Kepp, Peng Liu, Guido Kroemer, Lorenzo Galluzzi
Summary: BCL2 robustly maintains mitochondrial integrity, inhibits immune signaling and cell death, and limits the ability of dendritic cells to initiate adaptive immune responses, suggesting a universal immunosuppressive function for the mitochondrial immune checkpoint.
Article
Oncology
Shuai Zhang, Liwei Zhao, Mengfei Guo, Peng Liu, Sijing Li, Wei Xie, Ai-Ling Tian, Jonathan G. Pol, Hui Chen, Hui Pan, Misha Mao, Yumei Li, Laurence Zitvogel, Yang Jin, Oliver Kepp, Guido Kroemer
Summary: This study identified two small molecule drugs, ikarugamycin and astemizole, with immunotherapeutic potential. Ikarugamycin acts on DCs to enhance their antigen presenting ability, while astemizole activates T cells to strengthen immune response. Both drugs improved the anticancer activity of oxaliplatin.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Peng Liu, Liwei Zhao, Laurence Zitvogel, Oliver Kepp, Guido Kroemer
Summary: The BCL2 inhibitor venetoclax and genetic BCL2 inhibition exert their anticancer effects indirectly by enhancing the immune stimulatory function of dendritic cells and increasing tumor immunosurveillance through a T cell-mediated immune response.
CELL DEATH AND DIFFERENTIATION
(2023)