bims-caglex 2026-05-03 papers

Dermatol Ther (Heidelb). 2026 Apr 25.

Epigenetic Skin Aging and Its Reversal to Improve Skin Longevity across Ethnicities and Phototypes Using a Dihydromyricetin-Containing Serum: Results from a Prospective, Single-Cohort Study.

Minyue Qi, Paula Pitta, Katrin Wegner, Boris Kristof, Yan Feng, Günter Raddatz, Manuel Rodríguez-Paredes, Julia Gallinger, Rungsima Wanitphakdeedecha, Marc Winnefeld, Lilia Guadanhim, Cheri Frey, Frank Lyko, Cassandra Falckenhayn, Elke Grönniger.

INTRODUCTION: Skin aging is driven by intrinsic and extrinsic factors. Epigenetic alterations are one primary hallmark of aging and powerful biomarkers of biological skin age. To investigate epigenetic skin aging mechanisms and their regulation as a skin longevity approach across diverse ethnicities and phototypes, we assessed epidermal methylomes from white, African, and Asian donors.
METHODS: We collected epidermis samples from 17 multi-ethnic donors with diverse phototypes using a newly established tape-stripping method followed by array-based DNA methylation profiling to investigate the robustness of DNA methylation clocks across diverse ethnic backgrounds. Additionally, we conducted a clinical study with 60 participants representing Fitzpatrick phototypes I-VI. Diverse clinical parameters and biological skin age of the volunteers were determined at baseline and after applying a serum containing the natural epigenetic inhibitor dihydromyricetin (DHM) for 8 weeks to investigate skin longevity effects across phototypes.
RESULTS: Data analysis revealed that age-dependent DNA hypermethylation is conserved across populations and affects genes essential for keratinocyte vitality and longevity. A newly developed epidermal methylation clock accurately predicted biological age in multi-ethnic cohorts, confirming the robustness of epigenetic age estimation across phototypes. Topical application of a DHM-containing serum significantly reduced epidermal DNA methylation age. Epigenetic rejuvenation was associated with clinical improvements, including reduced skin roughness and wrinkle visibility and occupancy, and increased dermal echogenicity.
CONCLUSIONS: Together, these findings establish that epigenetic aging signatures are conserved across ethnicities and that targeted modulation using a DHM-containing topical formulation can reverse biological skin age while improving structural and visible signs of aging. This work provides the clinical evidence supporting epigenetic rejuvenation as a viable strategy for skin longevity across diverse populations.

Keywords: DNA methylation; Dihydromyricetin; Epigenetic age clock; Rejuvenation; Skin of color

DOI: https://doi.org/10.1007/s13555-026-01764-4

Mech Ageing Dev. 2026 Apr 23. pii: S0047-6374(26)00038-2. [Epub ahead of print]231 112186

Embryonic stem cell-derived extracellular vesicles alleviate ovarian dysfunction.

Xiang Li, Ru Ma, Mantong Zhao, Yu Guo, Xuemin Hu, Jinfeng Liu, Huaxin Yu, Zongjin Li, Xue Du, Na Liu.

BACKGROUND: Premature ovarian insufficiency (POI) causes irreversible follicular depletion and infertility, and current treatments do not reliably preserve fertility after gonadotoxic chemotherapy. Recent work suggests extracellular vesicles from embryonic stem cells (ESC-EVs) can promote tissue regeneration, but it is unknown whether ESC-EVs can prevent or reverse POI, and which cellular programs they engage to restore ovarian function.
METHODS: Here we tested ESC-EVs in a cyclophosphamide (Cy)-induced POI mouse model. We evaluated ovarian function by monitoring estrous cyclicity, follicle quantification, fertility, histology, fibrosis, and cellular senescence. We isolated granulosa cells for transcriptomic profiling to define ESC-EV-driven molecular changes.
RESULTS: ESC-EV treatment restored estrous cyclicity and improved fertility in Cy-induced mice, recovered follicle numbers, reduced stromal fibrosis and senescence marker expression, and activated estrogen‑responsive and gametogenesis gene programs. Granulosa cell transcriptomes showed reversal of Cy‑induced dysregulation of POI‑related genes (Figla, Nobox, Gdf9, Bmp15, Bcl2, Nfe2l2) and modulation of Nrf2 and DNA damage-response pathways.
CONCLUSIONS: ESC‑EVs rejuvenate the granulosa-oocyte niche by attenuating fibrosis and senescence and reactivating folliculogenic and estrogen‑responsive programs, thereby restoring ovarian function in a chemotherapy‑induced POI model. These results identify ESC‑EVs as a promising cell‑free regenerative approach for fertility preservation and ovarian rejuvenation.

Keywords: Embryonic stem cells; Extracellular vesicles; Ovarian aging; Premature ovarian insufficiency

DOI: https://doi.org/10.1016/j.mad.2026.112186

Aging Dis. 2026 Apr 29.

Peanut Procyanidin A Delays Hematopoietic Stem Cells Aging through Cox5a.

Ying Wang, Bingzheng Zhang, Junfei Lu, Lin Liu, Xiaoyu Tang, Changzheng Li, Xi Zeng, Chuqing Fan, Yuncong Qiao, Cheng Chen, Yu Zhang, Jiajia Chen, Zhiyi Li, Yucheng Luo, Guizhi Yang, Juan Shen, Bing Liu.

Hematopoietic stem cells (HSCs) are essential for maintaining blood system homeostasis. Their aging leads to functional decline and increased susceptibility to blood disorders, largely driven by elevated reactive oxygen species (ROS). Here, we identify peanut procyanidin A (PPA) as a potent compound that delays HSC aging by targeting cytochrome c oxidase subunit 5a (Cox5a). Through screening of 234 FDA-approved natural compounds, we found that PPA significantly reduces mitochondrial ROS and improves the function of aged HSCs in mice. Transcriptomic analysis revealed that PPA induces a metabolic shift from oxidative phosphorylation toward glycolysis, reminiscent of a youthful HSC state. Moreover, PPA rescues aging phenotypes in human CD34+ hematopoietic progenitor cells. Our study establishes Cox5a as a druggable target for HSC rejuvenation and highlights PPA as a promising therapeutic candidate for age-related hematopoietic decline.

DOI: https://doi.org/10.14336/AD.2025.1354

Phytomedicine. 2026 Apr 15. pii: S0944-7113(26)00437-X. [Epub ahead of print]156 158202

Tubeimoside Ⅰ targets sodium/potassium ATPase alpha 1 subunit to selectively eliminate senescent cells and alleviate aging-associated abnormalities.

Hao Jiang, Yuanyuan Xue, Zelong Miao, Yajun Zhang, Zhiqiang Li, Limeng Chen, Haiteng Deng.

BACKGROUND: Senescent cells accumulate with age and contribute to age-related diseases, which makes their selective elimination a promising strategy for therapeutic intervention. Tubeimoside I (TBMS1), a natural triterpenoid saponin derived from Bolbostemma paniculatum, has been extensively studied for its anticancer properties. However, its potential role as a senolytics has yet to be determined.
PURPOSE: This study elucidates the anti-aging effects and underlying mechanism of TBMS1 in vivo and in vitro.
METHODS: The anti-aging effects of TBMS1 were evaluated both in vitro and in vivo using CCK-8, senescence-associated β-galactosidase staining, immunofluorescence, flow cytometry, immunohistochemistry, and western blotting. Furthermore, its potential targets and underlying mechanism were investigated through thermal proteome profiling and comprehensive whole-proteome analysis.
RESULTS: We identified that TBMS1 is a senolytic agent. We identified that TBMS1 specifically targeted sodium/potassium-ATPase alpha 1 subunit (ATP1A1), a protein involved in maintaining ion homeostasis, which was highly expressed in senescent cells. TBMS1 modulated ATP1A1 activity, leading to altered intracellular potassium dynamics and disruption of ion homeostasis, which contributed to mitochondrial dysfunction and apoptosis in senescent cells. In vivo, TBMS1 improved motor function, reduced senescence markers, and alleviated tissue damage in both radiation-induced and naturally aged mouse models, without significant toxicity observed.
CONCLUSION: These findings position TBMS1 as a promising and mechanistically distinct senolytic candidate, offering new insights into ion homeostasis modulation as a therapeutic strategy for aging and senescence-related disorders.

Keywords: ATP1A1; Tubeimoside I; ion homeostasis; senescence; senolytics

DOI: https://doi.org/10.1016/j.phymed.2026.158202

Aging Cell. 2026 May;25(5): e70516

Replacement-Based Ageing Interventions for Systemic Rejuvenation: Shaping Longevity Science and Clinical Directions.

Bjorn Fraser Olaisen, Vadim N Gladyshev, Bohan Zhang, Anthony Atala, Kyle M Loh, Vera Gorbunova, Thomas A Rando, Tony Wyss-Coray, Eric Verdin, Alexander Zhavoronkov, Morten Scheibye-Knudsen, Sierra Lore, Daniela Bakula.

Biological and synthetic replacement-based ageing interventions hold substantial potential to reverse many forms of age-related damage simultaneously and extend healthy lifespan beyond what can be achieved with conventional therapeutics. In this Perspective, we discuss recent insights, unmet needs, and emerging trajectories that are catalysing research and clinical development of replacement-based treatments and synergistic strategies for multi-targeted damage removal and export at the molecular, organellar, and cellular levels. The first workshop dedicated to replacement as an ageing intervention at the Aging Research & Drug Discovery 2025 conference helped prioritise key challenges, opportunities, and future directions to address the need for preventive replacement and bioengineering technologies capable of inducing systemic and sustained rejuvenation across cells, tissues, and regulatory networks. We propose a roadmap to guide research and innovation integrating replacement and next-generation damage-removal therapeutics to modulate the ageing process in the whole body, restore biological function, and extend healthy lifespan.

DOI: https://doi.org/10.1111/acel.70516