bims-caglex 2026-01-04 papers

Pharmaceutics. 2025 Dec 09. pii: 1585. [Epub ahead of print]17(12):

A State-of-the-Art Overview on (Epi)Genomics and Personalized Skin Rejuvenating Strategies.

Roxana-Georgiana Tauser, Ioana-Mirela Vasincu, Andreea-Teodora Iacob, Maria Apotrosoaei, Bianca-Ștefania Profire, Florentina-Geanina Lupascu, Oana-Maria Chirliu, Lenuta Profire.

This article aims to point out new perspectives opened by genomics and epigenomics in skin rejuvenation strategies which target the main hallmarks of the ageing. In this respect, this article presents a concise overview on: the clinical relevance of the most important clocks and biomarkers used in skin anti-ageing strategy evaluation, the fundamentals, the main illustrating examples preclinically and clinically tested, the critical insights on knowledge gaps and future research perspectives concerning the most relevant skin anti-ageing and rejuvenation strategies based on novel epigenomic and genomic acquisitions. Thus the review dedicates distinct sections to: senolytics and senomorphics targeting senescent skin cells and their senescent-associated phenotype; strategies targeting genomic instability and telomere attrition by stimulation of the deoxyribonucleic acid (DNA) repair enzymes and proteins essential for telomeres' recovery and stability; regenerative medicine based on mesenchymal stem cells or cell-free products in order to restore skin-resided stem cells; genetically and chemically induced skin epigenetic partial reprogramming by using transcription factors or epigenetic small molecule agents, respectively; small molecule modulators of DNA methylases, histone deacetylases, telomerases, DNA repair enzymes or of sirtuins; modulators of micro ribonucleic acid (miRNA) and long-non-coding ribonucleic acid (HOTAIR's modulators) assisted or not by CRISPR-gene editing technology (CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats); modulators of the most relevant altered nutrient-sensing pathways in skin ageing; as well as antioxidants and nanozymes to address mitochondrial dysfunctions and oxidative stress. In addition, some approaches targeting skin inflammageing, altered skin proteostasis, (macro)autophagy and intercellular connections, or skin microbiome, are very briefly discussed. The review also offers a comparative analysis among the newer genomic/epigenomic-based skin anti-ageing strategies vs. classical skin rejuvenation treatments from various perspectives: efficacy, safety, mechanism of action, evidence level in preclinical and clinical data and regulatory status, price range, current limitations. In these regards, a concise overview on senolytic/senomorphic agents, topical nutrigenomic pathways' modulators and DNA repair enzymes, epigenetic small molecules agents, microRNAs and HOTAIRS's modulators, is illustrated in comparison to classical approaches such as tretinoin and peptide-based cosmeceuticals, topical serum with growth factors, intense pulsed light, laser and microneedling combinations, chemical peels, botulinum toxin injections, dermal fillers. Finally, the review emphasizes the future research directions in order to accelerate the clinical translation of the (epi)genomic-advanced knowledge towards personalization of the skin anti-ageing strategies by integration of individual genomic and epigenomic profiles to customize/tailor skin rejuvenation therapies.

Keywords: (epi)genomics; HOTAIR; antioxidants; epigenetic drugs; microRNA; personalized skin rejuvenation; photoageing; regenerative medicine; sirtuins; stem-cell exosomes

DOI: https://doi.org/10.3390/pharmaceutics17121585

bioRxiv. 2025 Dec 15. pii: 2025.12.11.693143. [Epub ahead of print]

Deep learning predicts haematopoietic stem cell ageing from 3D chromatin images.

Pablo Iáñez Picazo, Eva Mejía-Ramírez, Dario Di Bari, Elena Vitali, M Carolina Florian, Paula Petrone.

The functional decline of the haematopoietic system during ageing propagates detrimental effects on the whole organism, ultimately eroding life and healthspan. Quantifying haematopoietic ageing holds great scientific and clinical relevance. Alterations in chromatin architecture are a well-established hallmark of ageing that encode rich and informative signatures of the ageing process, yet they remain largely unexplored as quantitative markers. Here, we present an interpretable deep learning approach based on convolutional neural networks, ChromAgeNet, that learns changes in the spatial features of chromatin architecture during natural aging of Hematopoietic Stem Cells (HSCs). We trained our algorithm on 3D microscope images of DAPI-stained HSC nuclei to discriminate between young and aged murine HSCs, achieving and AUROC of 0.77 ± 0.03. This approach outperforms classical machine learning models trained on handcrafted chromatin features from the same dataset. We then applied explainable artificial intelligence techniques, identifying chromatin entropy, peripheral heterochromatin and chromatin condensates as predictive markers. As a proof of concept, we evaluated the potential of our model as a phenotypic screening tool for aged HSCs treated with epigenetic drugs to detect rejuvenation. Altogether, we demonstrate that changes in chromatin organization can be modeled via machine learning to predict cellular ageing in the hematopoietic compartment. Our developed framework, ChromAgeNet, serves as an interpretable algorithm to unravel the intricate relationship between chromatin changes and cellular ageing, and advance high throughput drug screening for rejuvenation therapies.

DOI: https://doi.org/10.64898/2025.12.11.693143

Aging Cell. 2026 Jan;25(1): e70343

A Histone Code Functionally Linked to Replicative Senescence.

Thomas Suter, Meyer J Friedman, Cagdas Tazearslan, Amir Gamliel, Daria Merkurjev, Kenneth Ohgi, Zhongjun Zhou, Michael G Rosenfeld, Yousin Suh.

Cell states and biological processes are defined by their epigenetic profiles, distinctive composites of DNA- and histone-based chromatin components. However, the specific histone posttranslational modifications that distinguish cellular senescence and the impact of their distribution on transcription, especially with regard to gene length, have not been fully elucidated. Here, we show that promoter loss of symmetric dimethylated H4R3 (H4R3me(2s)) and spreading of trimethylated H3K79 (H3K79me3) across gene bodies are functional features of replicative senescence associated with gene upregulation. We report that highly upregulated genes in replicative senescence exhibit enrichment of H3K79me3 and, in contrast to the characteristic trend of aging cells and tissues, are substantially longer than those that are significantly downregulated. Furthermore, by assessing all expressed genes, we demonstrate that gene body accumulation of H3K79me3 during the transition to replicative senescence constitutes a broader phenomenon that is positively correlated with gene length and expression level genome-wide. Consistently, pharmacological inhibition of H3K79me3 deposition attenuates gene upregulation in replicative senescence. We also document a striking increase in the levels of H3K79me3 as well as a robust H4R3me(2s) to asymmetric dimethylated H4R3 (H4R3me(2as)) epigenetic switch that manifest globally in late-passage cells, suggesting that these histone modifications might represent novel molecular biomarkers of replicative senescence. Finally, we implicate the associated epigenetic regulators, including DOT1L, PRMT1, PRMT5, and JMJD6, as modifiers of cellular lifespan, potentially disclosing unappreciated therapeutic targets for interventions in normal and pathological aging. Collectively, our findings provide novel insights into the histone code that mediates altered transcriptional regulation in replicative senescence.

Keywords: H3K79me3; H4R3me(2as); H4R3me(2s); aging; gene length; histone code; replicative senescence; transcription

DOI: https://doi.org/10.1111/acel.70343