Review
Biochemistry & Molecular Biology
Harvey Boughey, Mateusz Jurga, Sherif F. El-Khamisy
Summary: As we age, DNA mutations can lead to cellular dysfunction and aging, while naked mole rats show minimal biological decline and neurodegeneration despite their long lifespan.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Woei-Yaw Chee, Yuriko Kurahashi, Junhyeong Kim, Kyoko Miura, Daisuke Okuzaki, Tohru Ishitani, Kentaro Kajiwara, Shigeyuki Nada, Hideyuki Okano, Masato Okada
Summary: The study explores the unique mechanisms of cholesterol metabolism in naked mole-rat cells, which may contribute to their anti-senescent properties and longevity. Beta-catenin is identified as a key player in regulating cholesterol metabolism to offset senescence in naked mole-rats.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Stephan Emmrich, Alexandre Trapp, Frances Tolibzoda Zakusilo, Maggie E. Straight, Albert K. Ying, Alexander Tyshkovskiy, Marco Mariotti, Spencer Gray, Zhihui Zhang, Michael G. Drage, Masaki Takasugi, Jan-Henning Klusmann, Vadim N. Gladyshev, Andrei Seluanov, Vera Gorbunova
Summary: Research on naked mole rats' hematopoietic system found unique characteristics, such as an increased quiescent stem cell compartment, absence of age-related decline, and neotenic traits, which contribute to their longevity.
Article
Biology
Zhizhong Zheng, Rong Hua, Guoqiang Xu, Hui Yang, Peng Shi
Summary: This study provides new insights into the molecular basis of subterranean adaptations and highlights the importance of gene losses in mammalian evolution.
Article
Agriculture, Dairy & Animal Science
Kaori Oka, Masanori Yamakawa, Yoshimi Kawamura, Nobuyuki Kutsukake, Kyoko Miura
Summary: Naked mole-rats are long-lived rodents that exhibit delayed aging and resistance to age-related diseases. They live in underground colonies in hypoxic environments and have attracted significant interest from researchers in zoology and biomedicine.
ANNUAL REVIEW OF ANIMAL BIOSCIENCES
(2023)
Article
Multidisciplinary Sciences
Alison J. Barker, Grigorii Veviurko, Nigel C. Bennett, Daniel W. Hart, Lina Mograby, Gary R. Lewin
Summary: Naked mole-rats use specific vocalizations to transmit information about group membership, creating unique colony dialects. The integrity of these dialects is partially controlled by the queen and can be affected by changes in queen leadership. Pups raised in foreign colonies learn the vocal dialect of their adoptive colonies, showing the flexibility and vertical transmission of vocal signatures.
Article
Multidisciplinary Sciences
Csaba Kerepesi, Margarita Meer, Julia Ablaeva, Vince G. Amoroso, Sang-Goo Lee, Bohan Zhang, Maxim Gerashchenko, Alexandre Trapp, Sun Hee Yim, Ake T. Lu, Morgan E. Levine, Andrei Seluanov, Steve Horvath, Thomas J. Park, Vera Gorbunova, Vadim N. Gladyshev
Summary: The study reveals that naked mole-rats, despite having no increased mortality with age, experience epigenetic aging. By conducting bisulfite sequencing on the blood of over 100 naked mole-rats, researchers observe age-related methylome remodeling and loss of methylome information, indicating the aging process. An epigenetic clock is developed to accurately predict the age of naked mole-rats. These animals age at a much slower rate than mice but faster than humans, consistent with their known maximum lifespans.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Zhihui Zhang, Xiao Tian, J. Yuyang Lu, Kathryn Boit, Julia Ablaeva, Frances Tolibzoda Zakusilo, Stephan Emmrich, Denis Firsanov, Elena Rydkina, Seyed Ali Biashad, Quan Lu, Alexander Tyshkovskiy, Vadim N. Gladyshev, Steve Horvath, Andrei Seluanov, Vera Gorbunova
Summary: Abundant high-molecular-mass hyaluronic acid (HMM-HA) contributes to cancer resistance and longevity in naked mole-rats. A study showed that overexpressing the naked mole-rat hyaluronic acid synthase 2 gene (nmrHas2) in mice resulted in increased hyaluronan levels, reduced incidence of cancer, extended lifespan, and improved healthspan. The beneficial effects were mediated by HMM-HA and not specific to the nmrHas2 gene, suggesting that the longevity mechanism observed in naked mole-rats can be transferred to other species.
Article
Biochemistry & Molecular Biology
Hoi-Shan Wong, David A. Freeman, Yufeng Zhang
Summary: Evolutionary medicine is a rapidly developing field that utilizes non-traditional model organisms to gain valuable insights. The unique characteristics of naked mole-rats have attracted attention from various research areas, but their translational study to human research can be challenging. Damaraland molerats share common traits with naked mole-rats but have a higher degree of similarity to humans in certain physiological aspects, making them an alternative model organism for bridging the gap in biomedical research.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY
(2022)
Article
Computer Science, Artificial Intelligence
Rohit Salgotra, Supreet Singh, Urvinder Singh, Seyedali Mirjalili, Amir H. Gandomi
Summary: This paper proposes a hybrid algorithm MpNMRA, which combines the strengths of marine predator algorithm (MPA) and naked mole-rat algorithm (NMRA) to solve high-dimensional problems. Experimental results show that the proposed algorithm performs excellently in benchmark tests, as well as in solving real-world optimization problems and training multi-layer perceptrons.
EXPERT SYSTEMS WITH APPLICATIONS
(2023)
Article
Immunology
Ekaterina A. Gorshkova, Ekaterina O. Gubernatorova, Ekaterina M. Dvorianinova, Taisiya R. Yurakova, Maria V. Marey, Olga A. Averina, Susanne Holtze, Thomas B. Hildebrandt, Alexey A. Dmitriev, Marina S. Drutskaya, Mikhail Yu. Vyssokikh, Sergei A. Nedospasov
Summary: The immune system of the naked mole-rat possesses unique cellular composition and the ability of transcriptional and metabolic reprogramming in macrophages. However, the M1 phenotype of naked mole-rat macrophages shows species-specific signatures compared to murine M1.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Neurosciences
Hang Cheng, Matthew E. Pamenter
Summary: Naked mole-rat brain mitochondria exhibit greater tolerance to hypoxia and ischemia compared to mice, maintaining respiratory capacity and membrane integrity while avoiding redox disruptions. These findings suggest that naked mole-rats may serve as a natural model for investigating evolutionary solutions to ischemic pathology.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Multidisciplinary Sciences
M. Morevati, M. L. Mace, S. Egstrand, A. Nordholm, C. Doganli, J. Strand, J. L. Rukov, S. B. Torsetnes, V Gorbunova, K. Olgaard, E. Lewin
Summary: The Naked Mole Rat (NMR) serves as an interesting model for studying biomarkers of longevity due to its long lifespan. Research shows that the expression of the aging-suppressor gene Klotho is similar in both the kidneys of NMR and Rattus Norvegicus (RN), but with significant expression in the liver of NMR compared to RN. This suggests a potential role of hepatic extrarenal expression of Klotho as a longevity-related factor.
SCIENTIFIC REPORTS
(2021)
Article
Evolutionary Biology
Savandara Besse, Raphael Poujol, Julie G. Hussin
Summary: Naked mole-rats, the longest-lived rodents, exhibit strong resistance to oxidative stress and protein homeostasis, combating aging. Research has found differences between naked mole-rat and mouse proteins in aggregation propensity and mutation tolerance, potentially linked to the naked mole-rat's ability to delay aging.
GENOME BIOLOGY AND EVOLUTION
(2022)
Article
Multidisciplinary Sciences
Adeline Augereau, Marco Mariotti, Melanie Pousse, Doria Filipponi, Frederick Libert, Benjamin Beck, Vera Gorbunova, Eric Gilson, Vadim N. Gladyshev
Summary: The study reveals that the naked mole rat TRF1 supports maximal glycolytic capacity under low oxygen, showing increased nuclear localization and association with telomeres, and protecting them from replicative stress. The evolutionary gain of metabolic function in naked mole rat TRF1 is attributed to specific amino acid changes in the protein's homodimerization domain, while it also accelerates telomere shortening. This evolutionary strategy highlights an adaptation of telomere biology for metabolic control in extreme environments.
Article
Biochemistry & Molecular Biology
Bowen Song, Xuan Wang, Zhanmin Liang, Jiongming Ma, Daiyun Huang, Yue Wang, Joao Pedro de Magalhaes, Daniel J. Rigden, Jia Meng, Gang Liu, Kunqi Chen, Zhen Wei
Summary: Recent advances in epitranscriptomics have revealed the functional associations between RNA modifications (RMs) and multiple human diseases. This study presents an updated database, RMDisease v2.0, which identifies RM-associated genetic variants that may affect different types of RNA modifications in various organisms. These variants, including disease- and trait-associated genetic variants, may function through perturbations of epitranscriptomic markers. RMDisease v2.0 serves as a valuable resource for studying the genetic drivers of phenotypes in the epitranscriptome layer circuitry.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Oncology
Ines Marin, Olga Boix, Andrea Garcia-Garijo, Isabelle Sirois, Adria Caballe, Eduardo Zarzuela, Irene Ruano, Camille Stephan-Otto Attolini, Neus Prats, Jose A. Lopez-Dominguez, Marta Kovatcheva, Elena Garralda, Javier Munoz, Etienne Caron, Maria Abad, Alena Gros, Federico Pietrocola, Manuel Serrano
Summary: Senescent cells possess various features that make them highly efficient in stimulating dendritic cells and antigen-specific CD8 T cells, including the release of alarmins, activation of IFN signaling, enhanced MHC class I machinery, and presentation of specific self-peptides. Immunization with senescent cancer cells induces strong antitumor protection mediated by DCs and CD8 T cells, surpassing the effectiveness of immunization with cancer cells undergoing immunogenic cell death. Furthermore, induction of senescence in human primary cancer cells enhances their ability to activate autologous antigen-specific tumor-infiltrating CD8 lymphocytes. This study highlights the potential of exploiting senescent cancer cells to develop efficient and protective CD8-dependent antitumor immune responses.
Article
Cell Biology
Dominic F. Bennett, Anita Goyala, Cyril Statzer, Charles W. Beckett, Alexander Tyshkovskiy, Vadim N. Gladyshev, Collin Y. Ewald, Joao Pedro de Magalhaes
Summary: Searching for drugs with similar gene expression patterns, rilmenidine was found to extend the lifespan of nematodes and rats, mediated by the I1-imidazoline receptor. This study suggests the potential of rilmenidine as a longevity-promoting drug.
Article
Biochemistry & Molecular Biology
Jae-Hyun Yang, Motoshi Hayano, Patrick T. Griffin, Joao A. Amorim, Michael S. Bonkowski, John K. Apostolides, Elias L. Salfati, Marco Blanchette, Elizabeth M. Munding, Mital Bhakta, Yap Ching Chew, Wei Guo, Xiaojing Yang, Sun Maybury-Lewis, Xiao Tian, Jaime M. Ross, Giuseppe Coppotelli, Margarita V. Meer, Ryan Rogers-Hammond, Daniel L. Vera, Yuancheng Ryan Lu, Jeffrey W. Pippin, Michael L. Creswell, Zhixun Dou, Caiyue Xu, Sarah J. Mitchell, Abhirup Das, Brendan L. O'Connell, Sachin Thakur, Alice E. Kane, Qiao Su, Yasuaki Mohri, Emi K. Nishimura, Laura Schaevitz, Neha Garg, Ana-Maria Balta, Meghan A. Rego, Meredith Gregory-Ksander, Tatjana C. Jakobs, Lei Zhong, Hiroko Wakimoto, Jihad El Andari, Dirk Grimm, Raul Mostoslavsky, Amy J. Wagers, Kazuo Tsubota, Stephen J. Bonasera, Carlos M. Palmeira, Jonathan G. Seidman, Christine E. Seidman, Norman S. Wolf, Jill A. Kreiling, John M. Sedivy, George F. Murphy, Richard E. Green, Benjamin A. Garcia, Shelley L. Berger, Philipp Oberdoerffer, Stuart J. Shankland, Vadim N. Gladyshev, Bruce R. Ksander, Andreas R. Pfenning, Luis A. Rajman, David A. Sinclair
Summary: All living things experience increased entropy, resulting in the loss of genetic and epigenetic information. In yeast, this loss occurs due to the relocation of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity and age. Through the ICE system, it is found that faithful DNA repair accelerates aging at multiple levels, including the erosion of the epigenetic landscape and DNA methylation. However, this aging process can be reversed by OSK-mediated rejuvenation, supporting the information theory of aging.
Article
Biochemistry & Molecular Biology
Priyanka Raina, Rodrigo Guinea, Kasit Chatsirisupachai, Ines Lopes, Zoya Farooq, Cristina Guinea, Csaba-Attila Solyom, Joao Pedro de Magalhaes
Summary: Gene co-expression analysis is a powerful method for understanding gene function and regulation. The GeneFriends database provides researchers with updated gene co-expression networks for humans, mice, and other model organisms, based on RNA-seq data. This valuable tool can help researchers decipher the complexity of genomes and assign functions to poorly annotated genes.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yuxin Zhang, Jie Jiang, Jiongming Ma, Zhen Wei, Yue Wang, Bowen Song, Jia Meng, Guifang Jia, Joao Pedro de Magalhaes, Daniel J. Rigden, Daiyun Hang, Kunqi Chen
Summary: Mapping RNA modifications with advanced technologies has revolutionized our understanding of them. Current modification profiling methods are limited and require selective treatments. Direct RNA sequencing enables the direct study of modifications and has the potential to overcome the limitations of previous methods. The DirectRMDB database provides a fresh perspective on RNA modifications and allows exploration of the epitranscriptome in an isoform-specific manner.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemical Research Methods
Marcelo Rodrigues de Holanda Maia, Alexandre Plastino, Alex Freitas, Joao Pedro de Magalhaes
Summary: This paper proposes two new approaches for dealing with data uncertainty. One approach is to select training instances for each model in an ensemble, and the other is to sample features when splitting a node in a Random Forest training. These approaches are applied to classify ageing-related genes and predict drugs' side effects, and the results show that ensembles based on these approaches achieve better predictive performance.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2023)
Article
Multidisciplinary Sciences
Zhihui Zhang, Xiao Tian, J. Yuyang Lu, Kathryn Boit, Julia Ablaeva, Frances Tolibzoda Zakusilo, Stephan Emmrich, Denis Firsanov, Elena Rydkina, Seyed Ali Biashad, Quan Lu, Alexander Tyshkovskiy, Vadim N. Gladyshev, Steve Horvath, Andrei Seluanov, Vera Gorbunova
Summary: Abundant high-molecular-mass hyaluronic acid (HMM-HA) contributes to cancer resistance and longevity in naked mole-rats. A study showed that overexpressing the naked mole-rat hyaluronic acid synthase 2 gene (nmrHas2) in mice resulted in increased hyaluronan levels, reduced incidence of cancer, extended lifespan, and improved healthspan. The beneficial effects were mediated by HMM-HA and not specific to the nmrHas2 gene, suggesting that the longevity mechanism observed in naked mole-rats can be transferred to other species.
Article
Biochemistry & Molecular Biology
Xuan Wang, Yuxin Zhang, Kunqi Chen, Zhanmin Liang, Jiongming Ma, Rong Xia, Joao Pedro de Magalhaes, Daniel J. Rigden, Jia Meng, Bowen Song
Summary: With the advancement in mapping N7-methylguanosine (m(7)G) RNA methylation sites, a comprehensive resource (m7Ghub v.2.0) has been developed to study m(7)G modification under various physiological contexts. The resource includes the m7GDB database collecting hundreds of thousands of putative m(7)G sites identified in 23 species, the m7GDiseaseDB hosting m(7)G-associated variants including disease-relevant m(7)G-SNPs, and two enhanced analysis modules for interactive analyses.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Bohan Zhang, David E. Lee, Alexandre Trapp, Alexander Tyshkovskiy, Ake T. Lu, Akshay Bareja, Csaba Kerepesi, Lauren K. McKay, Anastasia V. Shindyapina, Sergey E. Dmitriev, Gurpreet S. Baht, Steve Horvath, Vadim N. Gladyshev, James P. White
Summary: Heterochronic parabiosis (HPB) is a technique that has rejuvenation effects on mouse tissues, reducing biological age and improving long-term health. In this study, mice exposed to young circulation through HPB showed reduced epigenetic aging, and this effect lasted even after the removal of youthful circulation. The transcriptomic and epigenomic profiles of these mice indicated a global rejuvenation effect. Furthermore, gene expression changes in the old HPB mice resembled those seen in interventions that extend lifespan. Overall, HPB results in lasting changes in epigenetic and transcriptomic profiles, leading to an extension of lifespan and health span.
Article
Cell Biology
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, David A. Sinclair
Summary: A hallmark of eukaryotic aging is a loss of epigenetic information, a process that can be reversed. By ectopically inducing the Yamanaka factors OCT4, SOX2, and KLF4 (OSK) in mammals, we can restore youthful characteristics without changing cellular identity. Through high-throughput cell-based assays, we have identified six chemical cocktails that can reverse cellular aging and rejuvenate human cells without altering the genome.
Article
Geriatrics & Gerontology
Ines Marin, Manuel Serrano, Federico Pietrocola
Summary: Recent reports provide strong evidence that senescent cells undergo surveillance by CD8 T cell-mediated adaptive immunity in both oncological and non-oncological experimental setups. These findings also reveal the mechanisms of sensitizing senescent cells to CD8 T cell-dependent killing and the mechanisms of senescent cell evasion from CD8 T cell immunosurveillance. Understanding the interplay between cellular senescence and the adaptive immune system could potentially lead to new strategies for mitigating aging and aging-associated diseases.
Article
Biochemical Research Methods
Jaime Martinez de Villarreal, Mark Kalisz, Gabriel Piedrafita, Osvaldo Grana-Castro, Dafni Chondronasiou, Manuel Serrano, Francisco X. Real
Summary: Transposable elements have played a major role in shaping mammalian genomes, but little is known about their cell-type-specific expression. A cost-efficient single-cell-resolution TE expression analytical approach is needed.
Article
Cell Biology
Cyril Lagger, Eugen Ursu, Anais Equey, Roberto A. Avelar, Angela Oliveira Pisco, Robi Tacutu, Joao Pedro de Magalhaes
Summary: Dysregulation of intercellular communication is a hallmark of aging. Here the authors provide a bioinformatics tool to infer changes in cell-cell signaling and an atlas of age-related communication changes in 23 mouse tissues.
Article
Cell Biology
A. T. Lu, Z. Fei, A. Haghani, T. R. Robeck, J. A. Zoller, C. Z. Li, R. Lowe, Q. Yan, J. Zhang, H. Vu, J. Ablaeva, V. A. Acosta-Rodriguez, D. M. Adams, J. Almunia, A. Aloysius, R. Ardehali, A. Arneson, C. S. Baker, G. Banks, K. Belov, N. C. Bennett, P. Black, D. T. Blumstein, E. K. Bors, C. E. Breeze, R. T. Brooke, J. L. Brown, G. G. Carter, A. Caulton, J. M. Cavin, L. Chakrabarti, I. Chatzistamou, H. Chen, K. Cheng, P. Chiavellini, O. W. Choi, S. M. Clarke, L. N. Cooper, M. L. Cossette, J. Day, J. DeYoung, S. DiRocco, C. Dold, E. E. Ehmke, C. K. Emmons, S. Emmrich, E. Erbay, C. Erlacher-Reid, C. G. Faulkes, S. H. Ferguson, C. J. Finno, J. E. Flower, J. M. Gaillard, E. Garde, L. Gerber, V. N. Gladyshev, V. Gorbunova, R. G. Goya, M. J. Grant, C. B. Green, E. N. Hales, M. B. Hanson, D. W. Hart, M. Haulena, K. Herrick, A. N. Hogan, C. J. Hogg, T. A. Hore, T. Huang, J. C. Izpisua Belmonte, A. J. Jasinska, G. Jones, E. Jourdain, O. Kashpur, H. Katcher, E. Katsumata, V. Kaza, H. Kiaris, M. S. Kobor, P. Kordowitzki, W. R. Koski, M. Kruetzen, S. B. Kwon, B. Larison, S. G. Lee, M. Lehmann, J. F. Lemaitre, A. J. Levine, C. Li, X. Li, A. R. Lim, D. T. S. Lin, D. M. Lindemann, T. J. Little, N. Macoretta, D. Maddox, C. O. Matkin, J. A. Mattison, M. McClure, J. Mergl, J. J. Meudt, G. A. Montano, K. Mozhui, J. Munshi-South, A. Naderi, M. Nagy, P. Narayan, P. W. Nathanielsz, N. B. Nguyen, C. Niehrs, J. K. O'Brien, P. O'Tierney Ginn, D. T. Odom, A. G. Ophir, S. Osborn, E. A. Ostrander, K. M. Parsons, K. C. Paul, M. Pellegrini, K. J. Peters, A. B. Pedersen, J. L. Petersen, D. W. Pietersen, G. M. Pinho, J. Plassais, J. R. Poganik, N. A. Prado, P. Reddy, B. Rey, B. R. Ritz, J. Robbins, M. Rodriguez, J. Russell, E. Rydkina, L. L. Sailer, A. B. Salmon, A. Sanghavi, K. M. Schachtschneider, D. Schmitt, T. Schmitt, L. Schomacher, L. B. Schook, K. E. Sears, A. W. Seifert, A. Seluanov, A. B. A. Shafer, D. Shanmuganayagam, A. V. Shindyapina, M. Simmons, K. Singh, I. Sinha, J. Slone, R. G. Snell, E. Soltanmaohammadi, M. L. Spangler, M. C. Spriggs, L. Staggs, N. Stedman, K. J. Steinman, D. T. Stewart, V. J. Sugrue, B. Szladovits, J. S. Takahashi, M. Takasugi, E. C. Teeling, M. J. Thompson, B. Van Bonn, S. C. Vernes, D. Villar, H. V. Vinters, M. C. Wallingford, N. Wang, R. K. Wayne, G. S. Wilkinson, C. K. Williams, R. W. Williams, X. W. Yang, M. Yao, B. G. Young, B. Zhang, Z. Zhang, P. Zhao, Y. Zhao, W. Zhou, J. Zimmermann, J. Ernst, K. Raj, S. Horvath
Summary: This study demonstrates the development of universal pan-mammalian clocks using DNA methylation profiles, accurately estimating the age of mammalian tissues. The age deviations are correlated with human mortality risk, mouse somatotropic axis mutations, and caloric restriction. The identification and characterization of evolutionarily conserved cytosine methylation patterns related to age highlight the interplay between aging and developmental processes across mammals.