bims-caglex 2025-08-10 papers

Geroscience. 2025 Aug 06.

EnsembleAge: enhancing epigenetic age assessment with a multi-clock framework.

Amin Haghani, Ake T Lu, Qi Yan, Juan Carlos Izpisua Belmonte, Pradeep Reddy, Victor Cheng, X William Yang, Nan Wang, Khyobeni Mozhui, Kevin Murach, Alejandro Ocampo, Robert W Williams, Mathias Jucker, Carina Bergmann, Jesse R Poganik, Bohan Zhang, Vadim N Gladyshev, Steve Horvath.

Several widely used epigenetic clocks have been developed for mice and other species, but a persistent challenge remains: different mouse clocks often yield inconsistent results. To address this limitation in robustness, we present EnsembleAge, a suite of ensemble-based epigenetic clocks. Leveraging data from over 200 perturbation experiments across multiple tissues, EnsembleAge integrates predictions from multiple penalized models. Empirical evaluations demonstrate that EnsembleAge outperforms existing clocks in detecting both pro-aging and rejuvenating interventions. Furthermore, we introduce EnsembleAge HumanMouse, an extension that enables cross-species analyses, facilitating translational research between mouse models and human studies. Together, these advances underscore the potential of EnsembleAge as a robust tool for identifying and validating interventions that modulate biological aging.

Keywords: Aging biomarkers; Biological age; DNA methylation; EnsembleAge; Epigenetic clocks; Healthspan; Lifespan interventions; MethylGauge dataset; Mouse models; Rejuvenation; Stress response

DOI: https://doi.org/10.1007/s11357-025-01808-1

Int J Nanomedicine. 2025 ;20 9573-9596

Recent Progress in Nano-TCM Active Ingredient Co-Delivery Systems for Inflammation-Mediated Diseases.

Chaoqun Sun, Ju Chen, Shuyou Bai, Wenyu Liao, Junmin Chen, Weixiong Guo, Li Zeng, Lili Yu.

Inflammation is a pivotal pathogenic factor in numerous diseases. Traditional Chinese medicine (TCM) has garnered significant attention due to its rich bioactive compounds with demonstrated anti-inflammatory and antioxidant activities. Nevertheless, clinical translation of TCM is often limited by poor pharmacokinetic properties, including low solubility, rapid clearance, and inadequate biomembrane permeability. Nanocarrier-based delivery systems have emerged as a promising strategy to overcome these limitations and enhance therapeutic outcomes. This review systematically summarizes: (1) the anti-inflammatory mechanisms of key TCM-derived compounds (resveratrol, quercetin, curcumin, honokiol, bergenin, ginsenosides, and berberine); (2) the classification and functional advantages of contemporary nanocarriers; and (3) recent advances in nanoengineered co-delivery systems for TCM active ingredients against inflammation-associated pathologies. Furthermore, we critically analyze persisting challenges and propose future directions to optimize nano-TCM platforms, offering new perspectives for targeted therapy of inflammatory diseases.

Keywords: inflammation-mediated diseases; nano-TCM co-delivery systems; nanocarrier; traditional Chinese medicine

DOI: https://doi.org/10.2147/IJN.S526731

Ageing Res Rev. 2025 Aug 02. pii: S1568-1637(25)00199-0. [Epub ahead of print] 102853

Telomerase Dynamics in Stem Cells: Unraveling the Molecular Nexus of Cellular Aging and Regeneration.

Yanhua Jiang, Yongjian Zhou, Yutao Wang, Zhe Li, Ghulam Md Ashraf, Liang Guo.

The expression levels of telomerase exhibit regulatory heterogeneity across different cell types and various biological stages of cell development. The expression of telomerase is dynamically regulated across cell types and developmental stages, with its activity predominantly determined by the abundance of its catalytic subunit, telomerase reverse transcriptase (TERT). Telomerase levels are typically high in the pluripotent embryonic stem cells, germline cells, and cancer cells, and silenced in the terminally differentiated cells. Minimal telomerase activity is present in the stem and progenitor cells of highly proliferative tissues, although preventing telomere shortening is beyond common sense in the field of biology and cannot be achieved, eventually leading to replicative senescence. While telomerase silencing in somatic cells and adult stem cells acts as a barrier to tumorigenesis by limiting their lifespan, the eventual exhaustion of stem cells pools leads to tissue dysfunction and aging. Telomerase reactivation through telomerase overexpression acted as the potential strategy to reverse stem cells aging and rejuvenate aged or dysfunctional tissues. In this review, we discuss the dynamics of telomere (length, activity, and expression level) in pluripotent and adult stem cells as well as their impact on aging. Notably, we have summarized the recent evidence in the application of mesenchymal stem cells immortalized through exogenous telomerase expression in regenerative medicine.

Keywords: Cellular aging; Cellular regeneration; Stem Cells; Telomerase reverse transcriptase

DOI: https://doi.org/10.1016/j.arr.2025.102853

bioRxiv. 2025 Jul 31. pii: 2025.07.28.667277. [Epub ahead of print]

SkeletAge: Transcriptomics-based Aging Clock Identifies 26 New Targets in Skeletal Muscle Aging.

Muhammad Ali, Fei Li, Manpreet Katari.

Identifying the set of genes that regulate baseline healthy aging - aging that is not confounded by illness - is critical to understating aging biology. Machine learning-based age-estimators (such as epigenetic clocks) offer a robust method for capturing biomarkers that strongly correlate with age. In principle, we can use these estimators to find novel targets for aging research, which can then be used for developing drugs that can extend the healthspan. However, methylation-based clocks do not provide direct mechanistic insight into aging, limiting their utility for drug discovery. Here, we describe a method for building tissue-specific bulk RNA-seq-based age-estimators that can be used to identify the ageprint . The ageprint is a set of genes that drive baseline healthy aging in a tissue-specific, developmentally-linked fashion. Using our age estimator, SkeletAge, we narrowed down the ageprint of human skeletal muscles to 128 genes, of which 26 genes have never been studied in the context of aging or aging-associated phenotypes. The ageprint of skeletal muscles can be linked to known phenotypes of skeletal muscle aging and development, which further supports our hypothesis that the ageprint genes drive (healthy) aging along the growth-development-aging axis, which is separate from (biological) aging that takes place due to illness or stochastic damage. Lastly, we show that using our method, we can find druggable targets for aging research and use the ageprint to accurately assess the effect of therapeutic interventions, which can further accelerate the discovery of longevity-enhancing drugs.

DOI: https://doi.org/10.1101/2025.07.28.667277