bims-caglex 2025-09-07 papers

MedComm (2020). 2025 Sep;6(9): e70369

Epigenetic Regulation of Aging and its Rejuvenation.

Yongpan An, Qian Wang, Ke Gao, Chi Zhang, Yanan Ouyang, Ruixiao Li, Zhou Ma, Tong Wu, Lifan Zhou, Zhengwei Xie, Rui Zhang, Guojun Wu.

Aging increases the global burden of disease, yet its molecular basis remains incompletely understood. Recent studies indicate that reversible epigenetic drift-spanning DNA methylation clocks, histone codes, three-dimensional chromatin, and noncoding RNA networks-constitutes a central regulator of organismal decline and age-related diseases. How these epigenetic layers interact across different tissues-and how best to translate them into therapeutic strategies-are still open questions. This review outlines the specific mechanisms by which epigenetic changes influence aging, highlighting their impact on genomic instability, stem-cell exhaustion, and mitochondrial dysfunction. We critically evaluate emerging rejuvenation strategies-partial OSKM reprogramming, CRISPR-dCas9 epigenome editing, NAD⁺/sirtuin boosters, HDAC inhibitors, microbiota transfer, and precision lifestyle interventions-detailing their efficacy in resetting epigenetic age and restoring tissue homeostasis. Integrating single-cell multiomics and second-generation epigenetic clocks, we propose a roadmap for translating these insights into safe, personalized antiaging medicine.

Keywords: aging; emerging rejuvenation strategies; epigenetic clocks; epigenetic mechanisms; epigenetic rejuvenation

DOI: https://doi.org/10.1002/mco2.70369

Cell Mol Life Sci. 2025 Aug 31. 82(1): 328

Interrogating the regulatory epigenome of cellular senescence.

Dimitris-Foivos Thanos, Orestis A Ntintas, Emmanouil I Athanasiadis, Angelos Papaspyropoulos, Russell Petty, Vassilis G Gorgoulis.

Chromatin, the spatial organizer of genomic DNA, is hierarchically folded into higher-order structures to facilitate DNA compaction, enabling genome surveillance. Understanding the organization and function of the three-dimensional (3D) genome is critical to profile chromatin accessibility and functional interactions that govern gene regulation across multiple biological processes, including aging and one of its hallmarks, cellular senescence. Cellular senescence constitutes a defensive stress response to various intrinsic and extrinsic stimuli, preserving cellular and organismal homeostasis through a generally irreversible cell cycle arrest. In this review article we discuss epigenetic alterations occurring to DNA and chromatin that drive and fuel the onset of this complex phenomenon. As such, we describe major large-scale chromatin events, including the formation of higher-order chromatin structures and the 3D spatial alterations of the genome that occur during senescence. We also discuss global heterochromatin loss, deficiencies in nuclear lamins, the depletion of core histones and their modifications, as well as the epigenetic regulation of the senescence-associated secretory phenotype (SASP), all of which serve key roles in the epigenome of senescent cells. To clearly demonstrate the significance of epigenetic modifications, data from a computational meta-analysis are presented, aiming to further underpin key epigenetic mechanisms occurring in senescent cells. Last, we highlight promising epigenetic modulators implemented in therapeutic strategies for senescent cell detection and elimination, possibly leading to significant clinical advances against various age-related diseases as well as the delay and prevention of the aging onset.

Keywords: Cellular senescence; Chromatin; Epigenetic modulators; Epigenetics

DOI: https://doi.org/10.1007/s00018-025-05848-w

Pharmacol Rep. 2025 Sep 02.

Epigenetic modulation in cancer drug discovery: promising targets and clinical applications.

Sundaram Vickram, Shofia Saghya Infant, Manikandan Sivasubramanian, Saravanan Anbalagan, Mathan Muthu Chinnakannu Marimuthu, Hitesh Chopra.

Epigenetic modulation has emerged as a central strategy that can change the fate of tumour cells to offer more rational and precise approaches by modulating reversible changes in chromatin structure, regulating gene expression without altering DNA sequence. Many reports have indicated the contributions of abnormal epigenetic alterations, particularly DNA methylation and histone modification patterns, as well as their association with non-coding RNA interactions during cancer emergence, development or resistance to standard therapies. Ongoing studies on various inhibitors also demonstrate encouraging preclinical results and potent inhibitory activity. Furthermore, combining epigenetic medicines with conventional treatment approaches such as chemotherapy and radiotherapy is proven to improve therapeutic efficacy in resistant cases of various malignancies. This article also briefly reviews RNA modifications (epitranscriptomics, such as m6A and m5C), novel acetylation modifications, chromosomal interaction studies, and the role of AlphaFold. The present review further illustrates these translational challenges and future opportunities in epigenetic drug development, while shedding light on the necessity of developing predictive biomarkers capable of informing personalized therapies to reduce off-target effects. The ability to target epigenetic modulators has the potential to improve patient outcomes and increase treatment options when coupled with traditional guidelines, as evidenced by on-going clinical trials and FDA approvals.

Keywords: Bromodomain-containing proteins (BRDs); Cancer drug discovery; Epigenetic inhibitors; Epigenetic modulation; Histone methyltransferases (HMTs); RNA modifications

DOI: https://doi.org/10.1007/s43440-025-00770-1