Article
Geriatrics & Gerontology
Lachlan Cribb, Allison M. Hodge, Chenglong Yu, Sherly X. Li, Dallas R. English, Enes Makalic, Melissa C. Southey, Roger L. Milne, Graham G. Giles, Pierre-Antoine Dugue
Summary: Limited evidence exists on the link between inflammation and epigenetic aging. This study found that most inflammation-related markers were associated with epigenetic aging cross-sectionally, but the association weakened after 11 years of follow-up. Epigenetic aging and inflammaging were both independently associated with mortality and can be used together to predict mortality.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Review
Cell Biology
Ying Lyu, Yejing Ge
Summary: Skin, the largest organ in the human body, undergoes aging processes such as wrinkling and hair graying, which are associated with epigenetic and metabolic deregulations. In the skin epithelium, the epigenome and metabolome play important roles in shaping cell lineage plasticity and regulating stem cell function during aging. This review summarizes recent studies on the molecular mechanisms of hair follicle degeneration, comparing findings from skin with model organisms and adult stem cells from other tissues.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maria Elisa Giuliani, Veronica Barbi, Giorgia Bigossi, Serena Marcozzi, Robertina Giacconi, Maurizio Cardelli, Francesco Piacenza, Fiorenza Orlando, Elena Ciaglia, Monica Cattaneo, Alessia Mongelli, Carlo Gaetano, Mauro Provinciali, Annibale Alessandro Puca, Marco Malavolta
Summary: This study found that the homozygous genotype of the Longevity-Associated Variant (LAV) in BPIFB4 is enriched in long-living individuals and gene transfer of LAV-BPIFB4 in aged mice showed improvements in aging biomarkers and health. These findings support the use of LAV-BPIFB4 gene therapy to induce beneficial effects on epigenetic mechanisms associated with aging and frailty in humans.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Natalia A. Prado, Janine L. Brown, Joseph A. Zoller, Amin Haghani, Mingjia Yao, Lora R. Bagryanova, Michael G. Campana, Jesus E. Maldonado, Ken Raj, Dennis Schmitt, Todd R. Robeck, Steve Horvath
Summary: Age-associated DNA-methylation profiles have been used to develop highly accurate biomarkers of age (epigenetic clocks) for African and Asian elephants. These clocks were developed using novel DNA methylation profiles of known age samples, and can be used for conservation efforts where accurate estimates of age are needed. Epigenome-wide association studies identified age-related CpGs and their proximal genes, revealing their importance in cellular differentiation, organismal development, metabolism, and circadian rhythms.
Article
Biochemistry & Molecular Biology
Zulfiya G. Guvatova, Anastasiya A. Kobelyatskaya, Elena A. Pudova, Irina V. Tarasova, Anna V. Kudryavtseva, Olga N. Tkacheva, Irina D. Strazhesko, Alexey A. Moskalev
Summary: This study estimated the epigenetic age of long-lived individuals and found that their epigenetic age was significantly lower than their chronological age, indicating a slowing of aging. However, there were no significant differences in epigenetic age between healthy long-lived individuals and those with frailty, and no differences in epigenetic age were observed based on sex. The study emphasizes the need for further research on the epigenetic status of centenarians.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Yun-Hsiang Lo, Wan-Yu Lin
Summary: This study comprehensively investigates the associations between cardiovascular health and four epigenetic clocks. The findings suggest that ideal cardiovascular health is associated with lower levels of biological aging, reducing the risk of aging-related disorders.
CLINICAL EPIGENETICS
(2022)
Article
Oncology
Xue-Yong Chang, Wan-Yu Lin
Summary: This study comprehensively investigates the role of five measures of epigenetic age acceleration (EAA) in mediating the associations of smoking with health outcomes in an Asian population. The results show that the second-generation epigenetic clocks (GrimEAA, DunedinPACE, and PhenoEAA) significantly mediate smoking associations with diabetes-related outcomes. In contrast, the first-generation epigenetic clocks (HannumEAA and IEAA) do not significantly mediate any associations of smoking variables with the four health outcomes. Cigarette smoking can directly and indirectly deteriorate human health through DNA methylation changes in aging-related CpG sites.
CLINICAL EPIGENETICS
(2023)
Article
Biochemistry & Molecular Biology
Marisol Fernandez-Ortiz, Ramy K. A. Sayed, Yolanda Roman-Montoya, Maria Angeles Rol de Lama, Jose Fernandez-Martinez, Yolanda Ramirez-Casas, Javier Florido-Ruiz, Iryna Rusanova, Germaine Escames, Dario Acuna-Castroviejo
Summary: This study investigated the impact of aging and NLRP3 expression on the cardiac circadian system, and found that melatonin can restore the rhythmicity of clock genes affected by age or NLRP3 activation, suggesting it as a promising therapy to placate inflammaging and restore circadian rhythm in heart muscle.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Shuai Wang, Yanke Lin, Lu Gao, Zemin Yang, Jingpan Lin, Shujing Ren, Feng Li, Jing Chen, Zhigang Wang, Zhiyong Dong, Pinghua Sun, Baojian Wu
Summary: Growing evidence suggests that circadian clock and obesity are intertwined, but the underlying mechanism is poorly understood. This study investigated the link between circadian clock and obesity, and found that obesity causes perturbance of the circadian clock in white adipose tissue (WAT). Reduced levels of glutamine and methionine in obese WAT were associated with decreased histone acetylation and methylation at the Bmal1 promoter. It was also found that impaired expression of PPAR-gamma in obesity led to downregulation of SLC1A5, resulting in reduced uptake of glutamine and methionine. These findings suggest that PPAR-gamma integrates obesity and adipocyte clock, promoting a vicious cycle between circadian disruption and obesity development.
Review
Cell Biology
Letizia Li Piani, Paola Vigano', Edgardo Somigliana
Summary: The increasing global life expectancy has led to more research on aging. Biological age, which takes into account both intrinsic and environmental factors, has gained more attention compared to chronological age. Epigenetic clocks, which are based on DNA methylation patterns and can estimate biological age, have gained significant attention in fertility research, particularly in terms of the relationship between epigenetic aging and women's infertility. Understanding this relationship may provide valuable insights into infertility mechanisms and pregnancy outcomes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Edward J. Calabrese, Naomi Osakabe, Rosanna Di Paola, Rosalba Siracusa, Roberta Fusco, Ramona 'Amico, Daniela Impellizzeri, Salvatore Cuzzocrea, Tilman Fritsch, Ali S. Abdelhameed, Uwe Wenzel, Claudio Franceschi, Vittorio Calabrese
Summary: This commentary provides a novel synthesis on the concept of hormesis, which proposes that adaptive responses to low levels of stress can enhance health and protect against degenerative diseases and aging. It emphasizes the quantitative limits of biological plasticity and the importance of integrating anti-oxidant, anti-inflammatory, and cellular repair responses. The hormetic dose response defines the capacity for adaptation and protection in biological systems.
AGEING RESEARCH REVIEWS
(2023)
Article
Multidisciplinary Sciences
Adiv A. Johnson, Nicole S. Torosin, Maxim N. Shokhirev, Trinna L. Cuellar
Summary: Epigenetic aging clocks are computational models that use DNA methylation sites to predict age. Researchers reviewed 11 existing clocks applied to buccal tissue and found that two were exclusively trained on adults and had moderate accuracy. They also generated a predictor using 130 common CpGs in an adult methylomic dataset, accurately estimating age and identifying health-related differences.
Article
Nutrition & Dietetics
Eva Untersmayr, Annette Brandt, Larissa Koidl, Ina Bergheim
Summary: The intestinal barrier, composed of various components, plays a critical role in health and disease, as well as during aging. Understanding the changes in the barrier function can provide insights into strategies for disease prevention in the elderly. Improving overall barrier function will be an important approach for promoting healthy aging in the future.
Article
Cell Biology
Jacob C. Johnson, Allyson S. Munneke, Haley M. Richardson, Christi M. Gendron, Scott D. Pletcher
Summary: Across taxa, sensory perception, including light, modulates aging in response to ecological cues. In Drosophila melanogaster, living in constant darkness significantly extends lifespan without affecting behavior or circadian rhythms. Flies lacking eyes or photoreceptor neurons are not affected by light, while transgenic activation of these neurons replicates the effects of environmental light on lifespan. The correlation between light and lifespan is not related to intensity, duration, or frequency of light-dark transitions, and high-intensity light reduces lifespan independently of non-specific damaging effects.
Article
Evolutionary Biology
Katharina J. Peters, Livia Gerber, Luca Scheu, Riccardo Cicciarella, Joseph A. Zoller, Zhe Fei, Steve Horvath, Simon J. Allen, Stephanie L. King, Richard C. Connor, Lee Ann Rollins, Michael Krutzen
Summary: The use of epigenetic clocks allows accurate age determination and sex prediction for Indo-Pacific bottlenose dolphins, providing a non-invasive method for extracting life history information.
EVOLUTIONARY APPLICATIONS
(2023)
Article
Oncology
Tanja Bozic, Chao-Chung Kuo, Jan Hapala, Julia Franzen, Monika Eipel, Uwe Platzbecker, Martin Kirschner, Fabian Beier, Edgar Jost, Christian Thiede, Wolfgang Wagner
Summary: The study proposed an alternative method to estimate MRD based on AML-associated DNA methylation patterns, which could reliably distinguish malignant and healthy samples by identifying abnormal DNAm patterns. However, since healthy samples may also contain abnormal-classified DNAm reads, the approach does not yet reliably differentiate between MRD positive and negative samples.
Article
Medical Laboratory Technology
Stephanie Sontag, Ledio Bocova, Wouter H. G. Hubens, Selina Nuechtern, Matthis Schnitker, Thomas Look, Kema M. Schroeder, Birgit Pluemaekers, Vithurithra Tharmapalan, Martina Wessiepe, Thomas Kraus, Jan Kramer, Lothar Rink, Steffen Koschmieder, Wolfgang Wagner
Summary: The study further optimized and validated targeted DNAm assays for leukocyte deconvolution using blood samples from healthy donors, ring trial participants, and patients with hematological diseases. Results showed that relative leukocyte quantification correlated with conventional blood counts using pyrosequencing or ddPCR, but outliers in epigenetic leukocyte counts were observed in some patients, especially those with hematopoietic malignancies. Further optimization of assays is needed for accurate absolute quantification.
CLINICAL CHEMISTRY
(2022)
Article
Medicine, Legal
J. Becker, P. Boehme, A. Reckert, S. B. Eickhoff, B. E. Koop, J. Blum, T. Guenduez, M. Takayama, W. Wagner, S. Ritz-Timme
Summary: The study directly compared age-associated DNA methylation patterns in German and Japanese donors, finding significant differences in certain CpG sites. However, the age prediction models based on multiple robust CpG sites did not reveal relevant differences between the two populations, suggesting the need for further research to ensure high quality age estimation.
INTERNATIONAL JOURNAL OF LEGAL MEDICINE
(2022)
Article
Oncology
Elmo W. I. Neuberger, Stephanie Sontag, Alexandra Brahmer, Keito F. A. Philippi, Markus P. Radsak, Wolfgang Wagner, Perikles Simon
Summary: Physical activity leads to an increase in cell-free DNA, with the majority of this DNA originating from granulocytes, which could compromise the accuracy of liquid biopsy.
CLINICAL EPIGENETICS
(2022)
Article
Engineering, Biomedical
Roman Goetzke, Giulio Abagnale, Burcu Yesilyurt, Lucia Salz, Olivia Cypris, Philipp Glueck, Sven Liesenfelder, Kira Zeevaert, Zhiyao Ma, Ronghui Li, Ivan G. Costa, Angelika Lampert, Vivek Pachauri, Uwe Schnakenberg, Martin Zenke, Wolfgang Wagner, Mohamed H. Elsafi Mabrouk, Marcelo A. S. Toledo
Summary: Colonies of induced pluripotent stem cells (iPSCs) exhibit self-organization and transition into 3D aggregates. This transition is characterized by gradual upregulation of specific genes and the formation of embryoid bodies (EBs). The use of polydimethylsiloxane (PDMS) pillars or micro-contact printing of vitronectin plays a role in spatial confinement and the formation of controlled size EBs without enzymatic or mechanical treatment.
Article
Medicine, Legal
F. Mayer, J. Becker, C. Reinauer, P. Boehme, S. B. Eickhoff, B. Koop, T. Guenduez, J. Blum, W. Wagner, S. Ritz-Timme
Summary: This study investigates the application of age estimation based on DNA methylation in healthy children and children with growth disorders. The findings suggest that growth disorders can impact epigenetic age predictions and CpGs in genes involved in growth and development should be avoided in age prediction models for children.
INTERNATIONAL JOURNAL OF LEGAL MEDICINE
(2022)
Article
Cell & Tissue Engineering
Marco Schmidt, Kira Zeevaert, Mohamed H. Elsafi Mabrouk, Roman Goetzke, Wolfgang Wagner
Summary: Quality control of induced pluripotent stem cells is challenging, and determining trilineage differentiation potential is crucial for validating their pluripotent state. In this study, GermLayerTracker, a combination of site-specific DNA methylation assays, was developed as a biomarker for early germ layer specification. Specific CG dinucleotides (CpGs) with characteristic DNA methylation patterns were identified in the pluripotent state and during differentiation into endoderm, mesoderm, and ectoderm. The GermLayerTracker can be used for quality control of pluripotent cells and to estimate lineage-specific commitment during initial differentiation events.
Review
Biochemistry & Molecular Biology
Deepika Puri, Wolfgang Wagner
Summary: Reprogramming towards pluripotency can rejuvenate cells, reversing age-associated molecular features and evading replicative senescence. However, complete reprogramming can lead to loss of cellular identity and risk of teratoma formation. Limited exposure to reprogramming factors can partially reset epigenetic ageing clocks while maintaining cellular identity. The relationship between rejuvenation and pluripotency, as well as alternative rejuvenation approaches, are discussed in this review.
Article
Engineering, Biomedical
Jose L. Gerardo-Nava, Jitske Jansen, Daniel Guenther, Laura Klasen, Anja Lena Thiebes, Bastian Niessing, Cedric Bergerbit, Anna A. Meyer, John Linkhorst, Mareike Barth, Payam Akhyari, Julia Stingl, Saskia Nagel, Thomas Stiehl, Angelika Lampert, Rudolf Leube, Matthias Wessling, Francesca Santoro, Sven Ingebrandt, Stefan Jockenhoevel, Andreas Herrmann, Horst Fischer, Wolfgang Wagner, Robert H. Schmitt, Fabian Kiessling, Rafael Kramann, Laura De Laporte
Summary: Recreating human tissues and organs in the petri dish to establish models as tools in biomedical sciences has gained momentum. Transformative materials play an important role in this evolution, as they can be programmed to direct cell behavior and fate. This paper illustrates state-of-the-art developments in in vitro tissue engineering and the challenges related to the design, production, and translation of transformative materials, emphasizing the need for convergence of different technologies to generate functional human tissue models.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Engineering, Biomedical
Prachi Desai, Anshuman Dasgupta, Alexandros Marios Sofias, Quim Pena, Robert Goestl, Ioana Slabu, Ulrich Schwaneberg, Thomas Stiehl, Wolfgang Wagner, Stefan Jockenhoevel, Julia Stingl, Rafael Kramann, Christian Trautwein, Tim H. Bruemmendorf, Fabian Kiessling, Andreas Herrmann, Twan Lammers
Summary: Drug delivery systems (DDS) control drug availability and activity to achieve a balance between therapeutic efficacy and side effects. They overcome biological barriers encountered by drug molecules and are explored for modulating host-material interfaces. This article provides an overview of barriers and interfaces encountered by DDS in different administration routes and highlights material engineering advances for improved disease treatment.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Oncology
Lucia Salz, Alexander Seitz, Daniel Schaefer, Julia Franzen, Tatjana Holzer, Carlos A. Garcia-Prieto, Iris Buerger, Olaf Hardt, Manel Esteller, Wolfgang Wagner
Summary: CAR T cell expansion during culture leads to DNA hypermethylation, which downregulates the expression of genes relevant to T cell function. This hypermethylation signature can predict cell culture time and is associated with reduced long-term survival and therapeutic outcome in CAR T cell products.
Article
Oncology
Ledio Bocova, Wouter Hubens, Cordula Engel, Steffen Koschmieder, Edgar Jost, Wolfgang Wagner
Summary: In this study, researchers demonstrate that hematopoietic stem and progenitor cells (HSPCs) can be estimated by targeted DNA methylation (DNAm) analysis. DNAm levels at specific CpG sites in the genes MYO1D, STK17A, and SP140 were found to correlate with CD34(+) cell numbers in mobilized peripheral blood and blast counts in leukemia. These epigenetic biomarkers could potentially be used to assess stem cell mobilization, HSPC harvesting, or blast count in leukemia.
CLINICAL EPIGENETICS
(2023)
Article
Pharmacology & Pharmacy
Henrike Jacobi, Margherita Vieri, Marlena Buetow, Carolina Y. Namasu, Laura Flueter, Ivan G. Costa, Tiago Maie, Katharina Lindemann-Docter, Nicolas Chatain, Fabian Beier, Michael Huber, Wolfgang Wagner, Martina Crysandt, Tim H. Bruemmendorf, Mirle Schemionek
Summary: The management of chronic myeloid leukemia (CML) has been revolutionized by tyrosine kinase inhibitors (TKIs), which can induce deep molecular responses and lead to treatment-free remission (TFR) in some patients. However, leukemic stem cells (LSCs) often persist and can cause relapse in patients attempting TKI discontinuation. This study shows that the presence of myelofibrosis (MF) at diagnosis is associated with TFR failure.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Oncology
Lara Rieh, Medhanie Mulaw, Katharina Kneer, Meinhard Beer, Ambros Beer, Thomas F. Bart, Vladimir Benes, Johannes Schulte, Matthias Fischer, Klaus-Michael Debatin, Christian Beltinger
Summary: In this study, tumor-associated mt and nuclear circulating variants were detected in a minority of NB patients, but the number and allelic frequency of the circulating variants did not reflect the clinical course of the tumors.
Article
Biotechnology & Applied Microbiology
Zhiyao Ma, Marcelo Augusto Szymanskide Toledo, Paul Wanek, Mohamed H. Elsafi Mabrouk, Francis Smet, Rock Pulak, Simon Pieske, Tobias Piotrowski, Werner Herfs, Christian Brecher, Robert H. Schmitt, Wolfgang Wagner, Martin Zenke
Summary: This article presents an automated platform for efficient and robust cultivation and differentiation of iPS cells into blood cells. By implementing cell cluster sorting and controlling the size of embryoid bodies (EBs), efficient differentiation of iPS cells can be achieved.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
