bims-caglex 2025-04-06 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2025–04–06
28 papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

Telomeres in skin aging.
Deguelin promotes longevity and healthspan through C. elegans fmo-4.
Targeting IGF1-Induced Cellular Senescence to Rejuvenate Hair Follicle Aging.
NIA Caenorhabditis Intervention Testing Program: identification of robust and reproducible pharmacological interventions that promote longevity across experimentally accessible, genetically diverse populations.
Counteracting Skin Aging In Vitro by Phytochemicals.
Inhibition of Ferroptosis Delays Aging and Extends Healthspan Across Multiple Species.
The rodent aging interventions database (RAID): a data visualization tool for all studies reporting rodent lifespan extension.
Youthful Brain-Derived Extracellular Vesicle-Loaded GelMA Hydrogel Promotes Scarless Wound Healing in Aged Skin by Modulating Senescence and Mitochondrial Function.
Mesenchymal stem cell-specific Sirt1 overexpression prevents sarcopenia induced by 1,25-dihydroxyvitamin D deficiency.
Intermittent fasting applied in combination with astaxanthin alleviates D-galactose-induced aging in rats: Comparison in oxidative stress, immune response, and metabolomics.
Senescent Endothelial Cells in Cerebral Microcirculation Are Key Drivers of Age-Related Blood-Brain Barrier Disruption, Microvascular Rarefaction, and Neurovascular Coupling Impairment in Mice.
Doxifluridine promotes host longevity through bacterial metabolism.
Determination via an Integration Strategy of the Potential Dermal ECM Reconstruction Mechanism by Which the WAW Formula Alleviates Skin Aging.
Life-long microbiome rejuvenation improves intestinal barrier function and inflammaging in mice.
Vorinostat attenuates UVB-induced skin senescence by modulating NF-κB and mTOR signaling pathways.
Mild activation of the mitochondrial unfolded protein response increases lifespan without increasing resistance to stress.
Poria cocos Polysaccharide Delays Aging by Enhancing the Antioxidant Ability and Suppressing the Expression of the Branched-Chain Amino Acid Transferase-Encoding Gene in Drosophila melanogaster.
Harnessing Immune Rejuvenation: Advances in Overcoming T Cell Senescence and Exhaustion in Cancer Immunotherapy.
Regeneration leads to global tissue rejuvenation in aging sexual planarians.
Melatonin hyalurosomes as a powerful antioxidant for combating skin damage induced by UV radiation.
Amelioration of aging-induced muscular decline by black soybean (Rhynchosia nulubilis) and black rice (Oryza sativa L.) extracts.
Engineered Extracellular Vesicles Derived from Juvenile Mice Enhance Mitochondrial Function in the Aging Bone Microenvironment and Achieve Rejuvenation.
Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity.
Simvastatin ameliorates senescence-induced mitochondrial dysfunction in vascular smooth muscle cells.
Alternate Day Fasting Enhances Intestinal Epithelial Function During Aging by Regulating Mitochondrial Metabolism.
Exploring Anti-Aging Potential of Dendrobium Species and Novel Microemulsion Delivery of Dendrobium kentrophyllum Extract for Anti-Aging Effect.
Targeting LKB1-AMPK-SIRT1-induced autophagy and mitophagy pathways improves cerebrovascular homeostasis in APP/PS1 mice.
In Vitro, Ex Vivo, Instrumental, and Clinical Assessment of a Novel Anti-aging Serum Targeting Oxidative Stress.

Biogerontology. 2025 Mar 30. 26(2): 83

Telomeres in skin aging.

Zibin Liu, Chang Sun, Zhaofeng Zhang, Yanfei Jiang, Chunyue Zhao.

  Skin aging is influenced by both intrinsic and extrinsic factors. The gradual manifestation of changes in telomere length and telomerase activity, as crucial indicators of aging, elucidates the underlying mechanism of skin aging. This review aims to comprehensively analyze the association between telomeres and aging, along with their impact on skin biological function. Firstly, we summarize the structure and function of telomeres and their role in cell division. Subsequently, we discuss the mechanisms through which telomere regulation contributes to aging processes while analyzing its involvement in skin aging by elaborating on biological markers. Furthermore, this paper presents a summary of recent research progress that reveals the correlation between telomere length and skin aging as well as model building methods; it also proposes telomere length as a potential indicator for predicting skin aging. Finally, anti-aging strategies based on telomere protection are discussed including drug therapy and lifestyle adjustments. This paper provides a systematic overview of the role played by telomeres in the field of skin aging for the first time, offering new perspectives and ideas for future prevention and treatment.

Keywords:  Anti-aging strategies; Cell aging; Skin aging; Telomerase; Telomeres

DOI:  https://doi.org/10.1007/s10522-025-10228-9
MicroPubl Biol. 2025 ;2025

Deguelin promotes longevity and healthspan through C. elegans fmo-4.

Angela M Tuckowski, Shijiao Huang, Kelly Chambers, Brandon Buscher, Scott F Leiser.

There are multiple approaches to longevity interventions in Caenorhabditis elegans , including genetic factors that are necessary or sufficient for lifespan extension and pharmacological agents that modify physiology to extend lifespan. Many pharmacological interventions act through known genetic pathways to promote longevity. Here, we show that the mitochondrial complex I inhibitor, deguelin, promotes lifespan extension and healthspan in an fmo-4- dependent manner. Our results confirm that deguelin increases lifespan and indicate that deguelin induces and requires multiple FMO enzymes to extend lifespan in C. elegans , suggesting these enzymes may promote longevity in a coordinated fashion.

DOI: https://doi.org/10.17912/micropub.biology.001548
Aging Cell. 2025 Mar 30. e70053

Targeting IGF1-Induced Cellular Senescence to Rejuvenate Hair Follicle Aging.

Yang Wang, Jian Yang, Yue Luo, Zhiqiang Zhao, Yawen Yuan, Juan Li, Yang Liu, Yong Yi, Xiaoke Xu, Yuankunyu Lan, Juan Zou, Qintong Li, Liang Wang, Yang Pan, Yuanhan Yang, Muzhao Xiong, Min Wu, Jinsong Li, Weiyuxin Li, Yujun Zhang, Yang Cao, Yi Zhu, Zhi-Xiong Jim Xiao.

  The insulin-like growth factor-1 (IGF-1) signaling pathway is known as a potent aging modifier, disruption of which consistently associates with lifespan extension across diverse species. Despite this established association, the mechanisms by which IGF-1 signaling modulates organ aging remain poorly understood. In this study, we assessed age-related changes in IGF-1 expression across multiple organs in mice and identified a more prominent increase in skin IGF-1 levels with aging-a phenomenon also observed in human skin. To explore the consequences of elevated IGF-1, we developed transgenic mice ectopically expressing human IGF-1 in the epidermis, driven by the bovine keratin 5 promoter (IGF-1 Tg). These mice exhibited premature aging of hair follicles, as evidenced by accelerated hair graying and loss. Single-cell RNA sequencing analyses of dorsal skin highlighted an upsurge in cellular senescence markers and the senescence-associated secretory phenotype (SASP) in hair follicle stem cells (HFSCs), alongside a decline in hair growth and HFSC exhaustion. Our findings indicate that excessive IGF-1 triggers HFSC senescence, thereby disrupting hair follicle homeostasis. Remarkably, interventions in IGF-1 signaling via downstream mechanisms-specifically blocking Ac-p53 activation via SIRT1 overexpression or senolytic treatment for senescent cell clearance, or reducing IGF-1 through dietary restriction-significantly reduced senescence markers, mitigated premature hair follicle aging phenotypes, and restored the stem cell pool. Our findings provide fundamental insights into the biological processes of hair aging and highlight the therapeutic promise of targeted interventions to rejuvenate aged HFSCs and promote hair follicle health.

Keywords:  IGF‐1; SIRT1; cellular senescence; dietary restriction; hair follicles; p53; senolytics

DOI:  https://doi.org/10.1111/acel.70053
Geroscience. 2025 Apr 03.

NIA Caenorhabditis Intervention Testing Program: identification of robust and reproducible pharmacological interventions that promote longevity across experimentally accessible, genetically diverse populations.

Monica Driscoll, Christine A Sedore, Brian Onken, Anna L Coleman-Hulbert, Erik Johnson, Patrick C Phillips, Gordon Lithgow.

  A core facet of the National Institute on Aging's mission is to identify pharmacological interventions that can promote human healthy aging and long life. As part of the comprehensive effort toward that goal, the NIA Division of Biology of Aging established the Caenorhabditis Intervention Testing Program (CITP) in 2013. The C. elegans model (with an ~ 21 day lifespan) has led the field in dissection of longevity genetics and offers features that allow for relatively rapid testing and for the potential elaboration of biological mechanisms engaged by candidate geroprotectants. CITP builds on this foundation by utilizing a genetically diverse set of intervention test strains so that "subjects" represent genetic diversity akin to that that between mouse and humans. Another distinctive aspect of the CITP is a dedicated focus on reproducibility of longevity outcomes as labs at three independent test sites confirm positive outcomes. The overall goal of the Caenorhabditis Intervention Testing Program (CITP) is to identify robust and reproducible pro-longevity interventions affecting genetically diverse cohorts in the Caenorhabditis genus. A strong Data Collection Center supports data collection and dissemination. Pharmacological interventions tested by CITP can be nominated by the general public, directed by in-house screens, or supported by published scientific literature. As of December 2024, CITP tested > 75 compounds and conducted > 725,000 animal assays over 891 trials. We identified 12 compounds that confer a ≥ 20% increase in median lifespan to reproducibly and robustly extend lifespan across multiple strains and labs. Five of these interventions have pro-longevity impact reported in the mouse literature (most CITP positive interventions are not tested yet in mouse). As part of the celebration of the 50th Anniversary of the NIA, we review the development history and accomplishments of the CITP program, and we comment on translation and the promise of advancing understanding of fundamental aging biology that includes the pharmacological intervention/health interface.

Keywords:   C. elegans ; Genetic diversity; Genetic model; Healthy aging; Pharmacological interventions; Pro-longevity; Reproducibility

DOI:  https://doi.org/10.1007/s11357-025-01627-4
J Cell Mol Med. 2025 Apr;29(7): e70530

Counteracting Skin Aging In Vitro by Phytochemicals.

Sara Cruciani, Giuseppe Garroni, Diletta Serra, Fikriye Fulya Kavak, Rosanna Satta, Fernanda Martini, Mauro Tognon, Carlo Ventura, Margherita Maioli.

  The skin is the most extensive organ in the human body. Photo exposure to ultraviolet (UV) rays causes several damages to skin cells, including premature skin aging, the onset of possible DNA mutations, and the risk of developing cancers, including melanoma. Protecting skin from the damaging effects of sun exposure through the application of creams and filters is important to prevent irreversible damages. Several natural extracts and biomolecules with antioxidant activity are widely used in the production of dietary supplements or topical products, for the prevention and treatment of skin affections. Within this context, we pre-treated human skin fibroblasts (HFF1), skin-isolated stem cells (SSCs) and keratinocytes (HaCaT) with two creams containing a specific solar protection factor (SPF) for 72 h and then exposed the cells to UV light. Gene expression analysis was performed for the key cell cycle regulators (p16, p19, p21, p53 and TERT). Cell senescence was assessed by colorimetric assays of beta-galactosidase and antioxidant potential, revealing the ability of treated cells to counteract free radical production as a result of oxidative stress. Finally, possible mutations in DNA induced by photo exposure were studied. The results obtained demonstrated that the tested products elicit positive effects on all skin cell populations, preserving them from photo exposure damages and premature senescence, being also able to increase the DNA repairing mechanisms and inducing a youngest phenotype.

Keywords:  antioxidants; bioactive molecules; cell senescence; fibroblasts; gene expression; repairing mechanisms; skin aging; stem cells

DOI:  https://doi.org/10.1111/jcmm.70530
Adv Sci (Weinh). 2025 Mar 31. e2416559

Inhibition of Ferroptosis Delays Aging and Extends Healthspan Across Multiple Species.

Hai-Jun Fu, Xing-Yue Zhou, Da-Lian Qin, Qan Qiao, Qiao-Zhi Wang, Shi-Ying Li, Yun-Fei Zhu, Ya-Ping Li, Jiang-Min Zhou, Hui Cai, Fei-Hong Huang, Lu Yu, Long Wang, An-Guo Wu, Jian-Ming Wu, Xiao-Gang Zhou.

  Ferroptosis, a form of iron-dependent cell death, plays a pivotal role in age-related diseases; yet, its impact on cellular senescence and healthspan in mammals remains largely unexplored. This study identifies ferroptosis as a key regulator of cellular senescence, showing that its inhibition can significantly delay aging and extend healthspan across multiple species. During cellular senescence, ferroptosis is progressively exacerbated, marked by increased lipid peroxidation, oxidative stress, and diminished glutathione peroxidase 4 (GPX4) levels. Ferroptosis inducers such as Erastin and RSL3 accelerate senescence; while, inhibitors such as liproxstatin-1 (Lip-1) and ferrostatin-1 (Fer-1) effectively mitigate both chemically and replicatively induced senescence. In vivo, Fer-1 extends lifespan and healthspan in Caenorhabditis elegans, enhances motor function, preserves tissue integrity, and mitigates cognitive decline in both prematurely and naturally aged mice. These effects are attributed to Fer-1's upregulation of GPX4 and inhibition of ferroptosis. Notably, long-term Fer-1 treatment (over 6 months) does not adversely affect body weight or induce aging-related tissue damage but rejuvenates hematological parameters. These findings establish ferroptosis as a critical player in aging dynamics and highlight its inhibition as a promising strategy to extend healthspan and lifespan, providing valuable insights for translational approaches to combat aging and age-related decline.

Keywords:  cellular senescence; ferroptosis; ferrostatin‐1; glutathione peroxidase 4; healthspan

DOI:  https://doi.org/10.1002/advs.202416559
Aging (Albany NY). 2025 Mar 27. 17

The rodent aging interventions database (RAID): a data visualization tool for all studies reporting rodent lifespan extension.

Maximus V Peto, Anthony J Floyd, Ben Zealley, Aubrey D N J de Grey.

  Numerous studies have investigated the effects of various interventions on the lifespans of mice and rats. The design of future rodent lifespan extension experiments might consider experimental parameters used in earlier investigations, but finding and reviewing all previous experiments requires a substantial resource investment. Additionally, when studied collectively, the results of previous investigations might suggest fundamental mechanisms causing age-related degeneration. Here, we report our efforts to find and aggregate data from all research reports of lifespan extension in mice or rats, which we call the "Rodent Aging Interventions Database" (RAID). We identified studies for inclusion using complex PubMed queries and by nomination from our colleagues in the field. The relevant data from each study was manually extracted and recorded in a table. A publicly available, web-based software tool was then created to enable users to visualize and filter this data in a convenient manner. Our current dataset, covering publications up to October 2022, includes 121 unique studies reporting on 212 distinct intervention protocols that extended lifespan in mice or rats. We intend to periodically update our dataset as new rodent lifespan studies are reported. RAID is publicly available at https://levf.org/raid.

Keywords:  databases; life extension; longevity; mice; rats

DOI:  https://doi.org/10.18632/aging.206228
Research (Wash D C). 2025 ;8 0644

Youthful Brain-Derived Extracellular Vesicle-Loaded GelMA Hydrogel Promotes Scarless Wound Healing in Aged Skin by Modulating Senescence and Mitochondrial Function.

Yuzhu Wu, Jiajie Mao, Yanyan Zhou, Gaoying Hong, Haiyan Wu, Zihe Hu, Xiaoyuan Huang, Jue Shi, Zhijian Xie, Yanhua Lan.

Slow wound healing in the elderly has attracted much attention recently due to the associated infection risks and decreased longevity. The "brain-skin axis" theory suggests that abnormalities in the brain and nervous system can lead to skin degeneration because abnormal mental states, like chronic stress, can have negative physiological and functional effects on the skin through a variety of processes, resulting in delayed wound healing and accelerated skin aging. However, it remains unclear whether maintaining a youthful brain has beneficial effects on aged skin healing. In light of this, we identified youthful brain-derived extracellular vesicles (YBEVs) and created a composite GelMA hydrogel material that encourages scarless wound healing in aged skin. We found that YBEVs reduce the expression of senescence, senescence-associated secretory phenotypes, and inflammation-associated proteins, and even restore dysfunction in senescent cells. Furthermore, by encouraging collagen deposition, angiogenesis, epidermal and dermal regeneration, and folliculogenesis, we demonstrated that YBEV-containing composite hydrogels accelerated scarless wound healing in skin wounds of aged rats. The pro-repairing speed and effect of this composite hydrogel even matched that of young rats. Subsequent proteomic analysis revealed the presence of numerous proteins within YBEVs, some of which may play a role in the regulation of skin energy intake, particularly through oxidative phosphorylation and mitochondrial function. In conclusion, the findings suggest that maintaining a youthful brain could potentially alleviate skin aging, and the proposed YBEVs-GelMA hydrogel emerges as a promising strategy for addressing age-related impairments in skin healing.

DOI: https://doi.org/10.34133/research.0644
Aging (Albany NY). 2025 Mar 31. null

Mesenchymal stem cell-specific Sirt1 overexpression prevents sarcopenia induced by 1,25-dihydroxyvitamin D deficiency.

Haiyun Chen, Biqi Ren, Jing Wang, Xingchen Liu, Xiangjiao Yi, David Goltzman, Dengshun Miao.

  Sarcopenia, characterized by an age-related decline in skeletal muscle mass and function, is closely linked to vitamin D deficiency. This study examines the role of Sirtuin 1 (Sirt1) and its regulation by vitamin D in preventing sarcopenia. Utilizing wild-type, 1α-hydroxylase knockout (1α(OH)ase-/-), and Sirt1 transgenic (Sirt1Tg) 1α(OH)ase-/- mice, we investigated muscle Sirt1 levels, muscle mass, fiber type, and senescence markers. Our results demonstrated that 1,25-Dihydroxyvitamin D (1,25(OH)2D3) upregulated Sirt1 and myogenic factor MyoD1 expression in C2C12 myoblasts via VDR-mediated transcription. Sirt1 overexpression in mesenchymal stem cells (MSCs) significantly mitigated muscle mass reduction, improved fiber cross-sectional area, and increased type II fiber numbers in 1α(OH)ase-/- mice. Mechanistically, 1,25(OH)2D3 promoted muscle cell health by enhancing Sirt1 expression, which in turn reduced muscle cell senescence and the senescence-associated secretory phenotype (SASP) through decreased levels of acetylated nuclear p53 and p65, maintaining their cytoplasmic localization. Additionally, Sirt1 overexpression accelerated muscle regeneration post-injury by increasing embryonic myosin heavy chain expression and cell proliferation. These findings underscore the therapeutic potential of targeting vitamin D and Sirt1 pathways to prevent sarcopenia, suggesting that supplementation with active vitamin D and consequent Sirt1 activation could be effective strategies for managing age-related muscle wasting.

Keywords:  Myod1; Sirt1; active vitamin D; muscle regeneration; sarcopenia

DOI:  https://doi.org/10.18632/aging.206232
J Food Sci. 2025 Apr;90(4): e70170

Intermittent fasting applied in combination with astaxanthin alleviates D-galactose-induced aging in rats: Comparison in oxidative stress, immune response, and metabolomics.

Zhiqing Chen, Jie Xiao, Kaixin Zhao, Yulu Lao, Han Liu, Yong Cao, Xiaojuan Liu.

  Effective anti-aging strategies involving dietary restriction and antioxidant supplementation are gaining increasing research attention, while the health effects of their combined intervention are rarely reported. In this study, for the first time, we investigated the anti-aging effects and underlying mechanisms of intermittent fasting (IF), astaxanthin (AX), and their combination in D-galactose-induced aging rats. Our results demonstrated that these three treatments effectively inhibited malondialdehyde levels and improved the activity of endogenous antioxidant enzymes in the brain, liver, and serum of aging rats. Simultaneously, the combination of IF and AX had a synergistic effect on the recovery of brain mitochondrial injury as evidenced by permeability transition pore openness, membrane potential, respiratory chain complex enzyme activity, and cortical and hippocampal lesions. Notably, the combination significantly increased the levels of Immunoglobulin M (55.66 ± 3.23%), immunoglobulin G (34.41 ± 2.65%), and IL-2 (23.49 ± 1.78%) compared with the model group. Moreover, AX reduced the accumulation of pro-inflammatory factor IL-6 (23.06 ± 2.02%), while the combination induced more remarkable reduction in the accumulation of IL-1β (35.92 ± 3.06%) in the serum. Considering the serum metabolomics analysis, we hypothesized that IF and AX played a positive role in the regulation of the nervous system, which was associated with the differential metabolites lysope 16:0, N-Acety-L-tyrosine, and L-Alanyl-L-Lysine. This research reveals that the combination therapy provided synergistic anti-aging efficacy by enhancing resistance to oxidative stress, ameliorating mitochondrial dysfunction, and restoring the immune system. These findings might have significant implications for further studies on the exploration of effective anti-aging therapy.

Keywords:  anti‐aging; astaxanthin; immune response; intermittent fasting; oxidative stress

DOI:  https://doi.org/10.1111/1750-3841.70170
Aging Cell. 2025 Apr 01. e70048

Senescent Endothelial Cells in Cerebral Microcirculation Are Key Drivers of Age-Related Blood-Brain Barrier Disruption, Microvascular Rarefaction, and Neurovascular Coupling Impairment in Mice.

Boglarka Csik, Ádám Nyúl-Tóth, Rafal Gulej, Roland Patai, Tamas Kiss, Jordan Delfavero, Raghavendra Y Nagaraja, Priya Balasubramanian, Santny Shanmugarama, Anna Ungvari, Siva Sai Chandragiri, Kiana Vali Kordestan, Mark Nagykaldi, Peter Mukli, Andriy Yabluchanskiy, Sharon Negri, Stefano Tarantini, Shannon Conley, Tae Gyu Oh, Zoltan Ungvari, Anna Csiszar.

  With advancing age, neurovascular dysfunction manifests as impaired neurovascular coupling (NVC), microvascular rarefaction, and blood-brain barrier (BBB) disruption, contributing to vascular cognitive impairment (VCI). Our previous research established a causal link between vascular senescence induced cerebromicrovascular dysfunction and cognitive decline in accelerated aging models. The present study examines whether chronological aging promotes endothelial senescence, adversely affecting neurovascular health, and whether senolytic therapies can enhance neurovascular function and cognitive performance in aged mice. We used transgenic p16-3MR mice to identify and eliminate senescent cells and employed genetic (ganciclovir) and pharmacological (ABT263/Navitoclax) senolytic approaches. Evaluations included spatial memory performance, NVC responses, cortical microvascular density, BBB permeability, and detection of senescent endothelial cells via flow cytometry. Brain endothelial cells exhibited heightened sensitivity to aging-induced senescence, undergoing senescence at a greater rate and earlier than other brain cell types, particularly during middle age. This microvascular endothelial cell senescence was associated with NVC dysfunction, microvascular rarefaction, BBB disruption, and deteriorating cognitive performance. On the other hand, senolytic treatments in aged mice improved NVC responses, BBB integrity, microvascular density, and learning capabilities. Notably, these findings suggest that the most effective time window for senolytic treatment is in middle-aged mice, where early intervention could better prevent neurovascular dysfunction and mitigate age-related cognitive impairment.

Keywords:  aging; blood–brain barrier; cerebral microvascular endothelial cells; neurovascular coupling; senescence; vascular cognitive impairment and dementia

DOI:  https://doi.org/10.1111/acel.70048
PLoS Genet. 2025 Mar 31. 21(3): e1011648

Doxifluridine promotes host longevity through bacterial metabolism.

Rui Wei, Yuling Peng, Yamei Luo, Xinyuan Wang, Zhenzhong Pan, Ran Zhou, Huan Yang, Zongyao Huang, Yaojia Liu, Lunzhi Dai, Yuan Wang, Yan Zhang.

Aging is associated with alternative splicing (AS) defects that have broad implications on aging-associated disorders. However, which drug(s) can rescue age-related AS defects and extend lifespan has not been systematically explored. We performed large-scale compound screening in C. elegans using a dual-fluorescent splicing reporter system. Among the top hits, doxifluridine, a fluoropyrimidine derivative, rescues age-associated AS defects and extends lifespan. Combining bacterial DNA sequencing, proteomics, metabolomics and the three-way screen system, we further revealed that bacterial ribonucleotide metabolism plays an essential role in doxifluridine conversion and efficacy. Furthermore, doxifluridine increases production of bacterial metabolites, such as linoleic acid and agmatine, to prolong host lifespan. Together, our results identify doxifluridine as a potent lead compound for rescuing aging-associated AS defects and extending lifespan, and elucidate drug's functions through complex interplay among drug, bacteria and host.

DOI: https://doi.org/10.1371/journal.pgen.1011648
J Cosmet Dermatol. 2025 Apr;24(4): e70124

Determination via an Integration Strategy of the Potential Dermal ECM Reconstruction Mechanism by Which the WAW Formula Alleviates Skin Aging.

Yingying Lin, Yunhee Chang, Yoojae Maeng, Xiaoxing Liu, Xinke Liu, Hong Meng, Fan Yi.

   BACKGROUND: Traditional Chinese medicine (TCM) treats skin conditions and delays aging using specific formulas. TCM links skin health to internal organ functions: kidney qi deficiency accelerates aging, whereas spleen deficiency leads to dry, loose skin from insufficient qi and blood. The renowned spleen-tonifying and kidney-nourishing formula "Wan An Wan" moisturizes the skin, but its antiageing mechanism remains unclear.
AIMS: The aim of this study was to investigate the development strategy and comprehensive methodological framework for incorporating TCM into cosmetics and to assess the mechanism of action and application potential of the WAW formula in mitigating skin aging.
RESULTS: In vitro experiments revealed that after optimizing the extraction of the active ingredients of the tailored WAW formula, it effectively inhibited NO production and tyrosinase activity and increased filaggrin, AQP, and HAS2 mRNA expression. Moreover, the active ingredients, including morroniside, were also analyzed separately. Mechanistic studies revealed that the tailored WAW formula upregulated the expression of the TGF-β1 gene associated with ECM production and downregulated the expression of the MMP-2/MMP-9 genes associated with ECM degradation, regulating cell behaviors such as migration, adhesion, and proliferation and thereby maintaining the healthy state of the skin.
CONCLUSIONS: In this study, an overall strategy for applying TCM for the development of skin care solutions was established, the potential value of WAW in modern dermatologic applications was revealed, innovative raw materials with comprehensive effects were developed, and new ideas for the fields of cosmetics and dermatology were provided.

Keywords:  ECM; WAW; integration strategy; skin aging; traditional Chinese medical formulas

DOI:  https://doi.org/10.1111/jocd.70124
Microbiome. 2025 Apr 02. 13(1): 91

Life-long microbiome rejuvenation improves intestinal barrier function and inflammaging in mice.

Felix Sommer, Joana P Bernardes, Lena Best, Nina Sommer, Jacob Hamm, Berith Messner, Víctor A López-Agudelo, Antonella Fazio, Georgios Marinos, A Samer Kadibalban, Go Ito, Maren Falk-Paulsen, Christoph Kaleta, Philip Rosenstiel.

   BACKGROUND: Alterations in the composition and function of the intestinal microbiota have been observed in organismal aging across a broad spectrum of animal phyla. Recent findings, which have been derived mostly in simple animal models, have even established a causal relationship between age-related microbial shifts and lifespan, suggesting microbiota-directed interventions as a potential tool to decelerate aging processes. To test whether a life-long microbiome rejuvenation strategy could delay or even prevent aging in non-ruminant mammals, we performed recurrent fecal microbial transfer (FMT) in mice throughout life. Transfer material was either derived from 8-week-old mice (young microbiome, yMB) or from animals of the same age as the recipients (isochronic microbiome, iMB) as control. Motor coordination and strength were analyzed by rotarod and grip strength tests, intestinal barrier function by serum LAL assay, transcriptional responses by single-cell RNA sequencing, and fecal microbial community properties by 16S rRNA gene profiling and metagenomics.
RESULTS: Colonization with yMB improved coordination and intestinal permeability compared to iMB. yMB encoded fewer pro-inflammatory factors and altered metabolic pathways favoring oxidative phosphorylation. Ecological interactions among bacteria in yMB were more antagonistic than in iMB implying more stable microbiome communities. Single-cell RNA sequencing analysis of intestinal mucosa revealed a salient shift of cellular phenotypes in the yMB group with markedly increased ATP synthesis and mitochondrial pathways as well as a decrease of age-dependent mesenchymal hallmark transcripts in enterocytes and TA cells, but reduced inflammatory signaling in macrophages.
CONCLUSIONS: Taken together, we demonstrate that life-long and repeated transfer of microbiota material from young mice improved age-related processes including coordinative ability (rotarod), intestinal permeability, and both metabolic and inflammatory profiles mainly of macrophages but also of other immune cells. Video Abstract.

Keywords:  Aging; Lifespan extension; Microbiome; Rejuvenation

DOI:  https://doi.org/10.1186/s40168-025-02089-8
Sci Rep. 2025 Mar 29. 15(1): 10905

Vorinostat attenuates UVB-induced skin senescence by modulating NF-κB and mTOR signaling pathways.

Qianlong Dai, Zhiwei Wang, Xue Wang, Wei Lian, Yuchen Ge, Shujia Song, Fuxing Li, Bingxiang Zhao, Lihua Li, Xiaobo Wang, Min Zhou, Jianjie Cheng.

  Excessive exposure to ultraviolet B (UVB) radiation induces oxidative stress and inflammatory responses, accelerating the senescence process of skin cells. Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is typically administered to patients with peripheral T-cell lymphoma, cutaneous T-cell lymphoma, or multiple myeloma. However, its effect on UVB-induced skin photoaging remains unclear. In this study, we used UVB to induce senescence in human immortalized keratinocyte cell line (HaCaT cells) and skin photoaging in Balb/c mice to investigate the potential of SAHA in mitigating photoaging. First, we established a UVB-induced photoaging model in HaCaT cells. We observed that UVB exposure significantly upregulated the activity of senescence-associated β-galactosidase, p16, p21, IL-1β, IL-6, and matrix metalloproteinases [collagenase (MMP-1), matrix metalloproteinase-3 (MMP-3), and gelatinase (MMP-9)]. Supplementation with SAHA effectively alleviated cellular senescence in HaCaT cells. Next, we used UVB to induce photoaging in Balb/c mouse skin. The study demonstrated that UVB markedly caused skin senescence in Balb/c mice, while SAHA effectively mitigated the changes induced by UVB irradiation. Mechanistically, we found that UVB activated the mammalian target of rapamycin (mTOR) and nuclear factor-κB (NF-κB) signaling pathways, whereas SAHA inhibited the upregulation of both mTOR and NF-κB. In summary, these findings suggest that SAHA may protect against UVB-induced cellular senescence and skin photoaging by inhibiting the mTOR and NF-κB signaling pathways. Therefore, SAHA could be a potential anti-senescence agent for mitigating skin photoaging.

Keywords:  Anti-photoaging; NF-κB; UVB-induced; Vorinostat; mTOR

DOI:  https://doi.org/10.1038/s41598-025-95624-4
Open Biol. 2025 Apr;15(4): 240358

Mild activation of the mitochondrial unfolded protein response increases lifespan without increasing resistance to stress.

Alexa Di Pede, Bokang Ko, Abdelrahman AlOkda, Aura A Tamez González, Shusen Zhu, Jeremy M Van Raamsdonk.

  The mitochondrial unfolded protein response (mitoUPR) is a stress response pathway that responds to mitochondrial insults by altering gene expression to recover mitochondrial homeostasis. The mitoUPR is mediated by the stress-activated transcription factor ATFS-1 (activating transcription factor associated with stress 1). Constitutive activation of ATFS-1 increases resistance to exogenous stressors but paradoxically decreases lifespan. In this work, we determined the optimal levels of expression of activated ATFS-1 with respect to lifespan and resistance to stress by treating constitutively active atfs-1(et17) worms with different concentrations of RNA interference (RNAi) bacteria targeting atfs-1. We observed the maximum lifespan of atfs-1(et17) worms at full-strength atfs-1 RNAi, which was significantly longer than wild-type lifespan. Under the conditions of maximum lifespan, atfs-1(et17) worms did not show enhanced resistance to stress, suggesting a trade-off between stress resistance and longevity. The maximum resistance to stress in atfs-1(et17) worms occurred on empty vector. Under these conditions, atfs-1(et17) worms are short-lived. This indicates that constitutive activation of ATFS-1 can increase lifespan or enhance resistance to stress but not both, at the same time. Overall, these results demonstrate that constitutively active ATFS-1 can extend lifespan when expressed at low levels and that this lifespan extension is not dependent on the ability of ATFS-1 to enhance resistance to stress.

Keywords:  ATFS-1; Caenorhabditis elegans; ageing; genetics; mitochondrial unfolded protein response; stress resistance

DOI:  https://doi.org/10.1098/rsob.240358
J Agric Food Chem. 2025 Apr 03.

Poria cocos Polysaccharide Delays Aging by Enhancing the Antioxidant Ability and Suppressing the Expression of the Branched-Chain Amino Acid Transferase-Encoding Gene in Drosophila melanogaster.

Kai Zhu, Dongsheng Du, Yuxia Shi, Fan Hu, Wenting Zhang, Hang Ni, Eqra Hafeez, Dongsheng Chen.

  Poria cocos polysaccharides (PCP), the main component of Poria cocos, possess a variety of biological activities, including antitumor, immunomodulatory, and antioxidant effects. However, whether PCP has an antiaging effect remains unclear. Here, we studied the beneficial effects and the mechanism of PCP on delaying aging using the Drosophila model. The results showed that the dietary supplementation of PCP significantly extended the lifespan, improved the climbing ability, attenuated intestinal barrier dysfunction, alleviated gastrointestinal acid-base imbalance, and prevented intestinal stem cells (ISCs) hyperproliferation. In addition, PCP notably increased the activities of SOD and CAT and reduced the content of MDA. Furthermore, RNA-Seq showed that PCP supplementation led to the differential expression of 638 genes. KEGG analysis revealed that these differentially expressed genes were strongly enriched in the signaling pathway of cofactor biosynthesis. Among these genes, the expression of the branched-chain amino acid transferase-encoding gene (bcat) was significantly downregulated. The bcat-knockdown prolonged the flies' lifespan, while bcat-overexpression reduced the lifespan. Interestingly, PCP addition can rescue the flies' lifespan in the background of bcat-overexpression. Taken together, our data indicate that PCP delays aging by enhancing the antioxidant ability and suppressing the expression of the bcat gene in Drosophila.

Keywords:  Drosophila melanogaster; Poria cocos polysaccharide; antiaging; antioxidant; bcat; intestinal homeostasis

DOI:  https://doi.org/10.1021/acs.jafc.4c12889
Aging Cell. 2025 Apr 03. e70055

Harnessing Immune Rejuvenation: Advances in Overcoming T Cell Senescence and Exhaustion in Cancer Immunotherapy.

Tesfahun Dessale Admasu, John S Yu.

  Immunotherapy has transformed the landscape of cancer treatment, with T cell-based strategies at the forefront of this revolution. However, the durability of these responses is frequently undermined by two intertwined phenomena: T cell exhaustion and senescence. While exhaustion is driven by chronic antigen exposure in the immunosuppressive tumor microenvironment, leading to a reversible state of diminished functionality, senescence reflects a more permanent, age- or stress-induced arrest in cellular proliferation and effector capacity. Together, these processes represent formidable barriers to sustained anti-tumor immunity. In this review, we dissect the molecular underpinnings of T cell exhaustion and senescence, revealing how these dysfunctions synergistically contribute to immune evasion and resistance across a range of solid tumors. We explore cutting-edge therapeutic approaches aimed at rewiring the exhausted and senescent T cell phenotypes. These include advances in immune checkpoint blockade, the engineering of "armored" CAR-T cells, senolytic therapies that selectively eliminate senescent cells, and novel interventions that reinvigorate the immune system's capacity for tumor eradication. By spotlighting emerging strategies that target both exhaustion and senescence, we provide a forward-looking perspective on the potential to harness immune rejuvenation. This comprehensive review outlines the next frontier in cancer immunotherapy: unlocking durable responses by overcoming the immune system's intrinsic aging and exhaustion, ultimately paving the way for transformative therapeutic breakthroughs.

Keywords:  CAR‐T; T cell exhaustion; T cell senescence; immune checkpoints; immune rejuvenation; immunosenescence; immunotherapy; senolytic therapy; solid tumors

DOI:  https://doi.org/10.1111/acel.70055
Nat Aging. 2025 Apr 03.

Regeneration leads to global tissue rejuvenation in aging sexual planarians.

Xiaoting Dai, Xinghua Li, Alexander Tyshkovskiy, Cassandra Zuckerman, Nan Cheng, Peter Lin, David Paris, Saad Qureshi, Leonid Kruglyak, Xiaoming Mao, Jayakrishnan Nandakumar, Vadim N Gladyshev, Scott Pletcher, Jacob Sobota, Longhua Guo.

The possibility of reversing the adverse impacts of aging could significantly reduce age-related diseases and improve quality of life in older populations. Here we report that the sexual lineage of the planarian Schmidtea mediterranea exhibits physiological decline within 18 months of birth, including altered tissue architecture, impaired fertility and motility, and increased oxidative stress. Single-cell profiling of young and older planarian heads uncovered loss of neurons and muscle, increase of glia, and revealed minimal changes in somatic pluripotent stem cells, along with molecular signatures of aging across tissues. Remarkably, amputation followed by regeneration of lost tissues in older planarians led to reversal of these age-associated changes in tissues both proximal and distal to the injury at physiological, cellular and molecular levels. Our work suggests mechanisms of rejuvenation in both new and old tissues concurring with planarian regeneration, which may provide valuable insights for antiaging interventions.

DOI: https://doi.org/10.1038/s43587-025-00847-9
J Liposome Res. 2025 Apr 01. 1-16

Melatonin hyalurosomes as a powerful antioxidant for combating skin damage induced by UV radiation.

Mariam Zewail, Haidy Abbas, Merhan E Ali, Shaimaa Makled.

  Extrinsic skin aging is caused by chronic skin photodamage. The present study aims to inspect the role of nanoencapsulation of melatonin (MEL) in hyalurosomes in combating UVB-induced skin damage to take advantage of the hydrating penetration enhancing and antiaging effects of hyaluronic acid along with the powerful antioxidant effects of MEL. Measurement of particle size, zeta potential, encapsulation efficiency and in vitro MEL release were carried out. The in vivo photoprotective effects of MEL were tested in rats. A histopathological examination was conducted, and antioxidant and anti-inflammatory markers were measured along with estimating the expression of P38 MAPK, P-ERK and P-JNK. Particle size and zeta potential of MEL hyalurosomes were 285.9 nm and -26.3 mV with 95% entrapment efficiency and provided a sustained release profile for 48h. In vivo, results revealed the superior effect of MEL hyalurosomes in protecting skin against UVB-induced damage and reducing the levels of inflammatory mediators like TNF-α and IL6 compared with MEL suspension. However, they had a prominent role in increasing the levels of antioxidants. These findings may be accredited to the effect of nanoencapsulation in enhancing skin penetration and deposition of MEL besides the effect of hyaluronic acid as a powerful antiaging tool.

Keywords:  UVB; Wrinkles; anti-aging; hyaluronic acid; melatonin; vesicular systems

DOI:  https://doi.org/10.1080/08982104.2025.2484732
Front Immunol. 2025 ;16 1554941

Amelioration of aging-induced muscular decline by black soybean (Rhynchosia nulubilis) and black rice (Oryza sativa L.) extracts.

Hyejeong Park, Seungmin Yu, Wooki Kim.

  Aging leads to a decline in the mass and function of skeletal muscles, a condition known as sarcopenia. It was previously reported that aging-related alterations in protein degradation, chronic inflammation, and deterioration of mitochondrial metabolism affect the acceleration of muscle atrophy in the elderly. However, the detailed mechanism or substantial causes for age-related muscle loss are still lacking, yet exercise or an increment in dietary protein intake are suggested as effective approaches to mitigate muscle atrophy. This study aims to investigate the regulatory effect of black soybean (Rhynchosia nulubilis) and black rice (Oryza sativa L.) mixture extract (BBME), which are rich in protein and bioactive compounds, in 12-month-old aged mice and L6 myotubes. BBME was orally administered at 300 and 600 mg/kg/day (low and high doses) for 12 weeks, and its effects on systemic glucose homeostasis and skeletal muscle metabolism were evaluated. Consequently, BBME at a high dose marginally ameliorated muscle loss and significantly improved glucose metabolism. BBME also reduced cellular senescence markers and enhanced mitochondrial biogenesis in aged skeletal muscles. Additionally, BBME exerted insulin-like activity by promoting glucose metabolism in L6 myotubes. These findings suggest the potential of BBME as a functional food ingredient in alleviating aging-induced muscle loss by modulating mitochondrial activity and glucose metabolism.

Keywords:  diet; energy metabolism; mitochondria; phytochemical; sarcopenia

DOI:  https://doi.org/10.3389/fimmu.2025.1554941
ACS Nano. 2025 Apr 04.

Engineered Extracellular Vesicles Derived from Juvenile Mice Enhance Mitochondrial Function in the Aging Bone Microenvironment and Achieve Rejuvenation.

Jiaqian Zheng, Yipeng Ren, Junhua Ke, Guanglin Zhu, Zhen Wang, Xuetao Shi, Yingjun Wang.

  Aging-related bone degeneration and impaired healing capacity remain significant challenges in regenerative medicine, necessitating innovative, efficient, and targeted strategies to restore bone health. Here, we engineered extracellular vesicles (EVs) derived from the serum of pretreated juvenile mice, with the goals of reversing aging, enhancing osteogenic potential, and increasing bioavailability to rejuvenate the aging bone environment. First, we established bone healing models representing different phases of healing to identify the EV type with the highest potential for improving the bone microenvironment in older individuals. Second, we employed DSS6 for bone targeting to enhance the biological effects of the selected EVs in vivo. The engineered EVs effectively targeted bone repair sites and promoted fracture healing more effectively than unmodified EVs in older mice. RNA sequencing revealed that the translocase of outer mitochondrial membrane 7 (Tomm7) is crucial for the underlying mechanism. Silencing Tomm7 significantly diminished the positive regulatory effects of the EVs. Specifically, the engineered EVs may enhance mitochondrial function in aging cells by activating the Tomm7-mediated Pink1/Parkin mitophagy pathway, promoting stemness recovery in aging bone marrow stromal cells (BMSCs) and reversing the adverse conditions of the aging bone microenvironment. Overall, the developed engineered EVs derived from serum from juvenile mice offer an alternative approach for treating aging bones. The identified underlying biological mechanisms provide a valuable reference for precision treatment of aging bones in the future.

Keywords:  aging tissue rejuvenation; bone-targeting; extracellular vesicles; mitophagy; rejuvenation

DOI:  https://doi.org/10.1021/acsnano.4c17989
Mol Brain. 2025 Mar 28. 18(1): 27

Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity.

Mohammed R Shaker, Salam Salloum-Asfar, Rowaida Z Taha, Ibrahim Javed, Ernst J Wolvetang.

  Klotho, a well-known aging suppressor protein, has been implicated in neuroprotection and the regulation of neuronal senescence. While previous studies have demonstrated its anti-aging properties in human brain organoids, its potential to mitigate neurodegenerative processes triggered by β-amyloid remains underexplored. In this study, we utilised human induced pluripotent stem cells (iPSCs) engineered with a doxycycline-inducible system to overexpress KLOTHO and generated 2D cortical neuron cultures from these cells. These neurons were next exposed to pre-aggregated β-amyloid 1-42 oligomers to model the neurotoxicity associated with Alzheimer's disease. Our data reveal that upregulation of KLOTHO significantly reduced β-amyloid-induced neuronal degeneration and apoptosis, as evidenced by decreased cleaved caspase-3 expression and preservation of axonal integrity. Additionally, KLOTHO overexpression prevented the loss of dendritic branching and mitigated reductions in axonal diameter, hallmark features of neurodegenerative pathology. These results highlight Klotho's protective role against β-amyloid-induced neurotoxicity in human cortical neurons and suggest that its age-related decline may contribute to neurodegenerative diseases such as Alzheimer's disease. Our findings underscore the therapeutic potential of Klotho-based interventions in mitigating age-associated neurodegenerative processes.

Keywords:  Alzheimer’s disease; Cortical neurons; Klotho; Neurodegeneration; Neuroprotection; iPSCs; β-amyloid

DOI:  https://doi.org/10.1186/s13041-025-01199-6
Atherosclerosis. 2025 Mar 21. pii: S0021-9150(25)00074-7. [Epub ahead of print]403 119176

Simvastatin ameliorates senescence-induced mitochondrial dysfunction in vascular smooth muscle cells.

C Rossi, C Macchi, C D'Alonzo, M Venturin, M Ruscica, A Corsini, C Battaglia, S Bellosta.

   BACKGROUND AND AIMS: Senescence and mitochondrial dysfunction are two major indicators of aging. Mitochondria are potential drivers of aging phenotypes and dysfunctional mitochondria are associated with several age-related diseases. There is evidence that senescence induces changes in mitochondrial structure, dynamics, and function. Moreover, senescent vascular smooth muscle cells (VSMCs) are present in atherosclerotic plaques and contribute to their instability. The anti-atherosclerotic effects of simvastatin are well known, but recently other benefits, such as promoting mitochondrial quality and senostatic effects, have been hypothesized. We aimed to analyze simvastatin's senostatic effects in senescent VSMCs.
METHODS: We established and characterized mitochondrial dysfunction in doxorubicin-induced senescent VSMCs (doxorubicin) or VSMCs serially passaged to induce replicative senescence (old).
RESULTS: We observed in both senescent models few typical senescence markers such as altered cell morphology, cell cycle inhibitors, laminB1, an accumulation of dysfunctional mitochondria characterized by reduced mitochondrial membrane potential (MMP) and respiration, accumulation of reactive oxygen species (ROS), and an altered mitochondria morphology. Down-regulation of TFAM and TOM70 expression was observed only in old cells suggesting a reduction of mitochondrial biogenesis. Next, we investigated whether simvastatin could ameliorate age-associated phenotypes in senescent VSMCs. Simvastatin 0.1 μM reduces the senescence-associated secretory phenotype (SASP) and ROS production and improves mitochondrial respiration in doxorubicin and old VSMCs. Interestingly, the effects of simvastatin on mitochondrial respiration and SASP were replicated by using a siRNA for the hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, and abolished by adding mevalonic acid, suggesting that these effects are mediated through the inhibition of HMG-CoA reductase.
CONCLUSIONS: Our results suggest that simvastatin controls SASP and exerts potentially beneficial therapeutic effects by ameliorating senescence-induced mitochondrial dysfunction in senescent VSMCs.

Keywords:  Aging; Mitochondrial dysfunction; Senescence; Statins; Vascular smooth muscle cells

DOI:  https://doi.org/10.1016/j.atherosclerosis.2025.119176
Aging Cell. 2025 Apr 01. e70052

Alternate Day Fasting Enhances Intestinal Epithelial Function During Aging by Regulating Mitochondrial Metabolism.

Heng Quan, Yao Lu, Yingying Lin, Peng Xue, Yuning Zhang, Yuqi Wang, Weiru Yu, Xiaoya Lin, Wuqi Yang, Cong Lv, Yafei Zhang, Fazheng Ren, Huiyuan Guo.

  With advancing age, the decline in intestinal stem cell (ISC) function can lead to a series of degenerative changes in the intestinal epithelium, a critical factor that increases the risk of intestinal diseases in the elderly. Consequently, there is an urgent imperative to devise effective dietary intervention strategies that target the alterations in senescent ISCs to alleviate senescence-related intestinal dysfunction. The 28-month-old naturally aging mouse model was utilized to discover that the primary factor contributing to the compromised barrier function and digestive absorption of the small intestine was a decrease in both the number and regenerative capacity of ISCs. The underlying mechanism involves the degeneration of mitochondrial function in ISCs, resulting in insufficient energy supply and decreased metabolic capacity. Additionally, our findings indicate that fasting-refeeding can influence the mitochondrial metabolism of ISCs, and that alternate day fasting (ADF) can facilitate the restoration of both the quantity and regenerative capabilities of ISCs, thereby exhibiting a notable antiaging effect on the small intestine. In conclusion, this study provides new insights into the potential beneficial role of ADF in ameliorating intestinal aging, thereby establishing a foundation for future investigations into dietary interventions aimed at addressing age-related intestinal dysfunction.

Keywords:  aging; alternate day fasting; gut; intestinal stem cell; mitochondrial metabolism

DOI:  https://doi.org/10.1111/acel.70052
Nanotechnol Sci Appl. 2025 ;18 157-171

Exploring Anti-Aging Potential of Dendrobium Species and Novel Microemulsion Delivery of Dendrobium kentrophyllum Extract for Anti-Aging Effect.

Suradwadee Thungmungmee, Boonchoo Sritularak, Nakuntwalai Wisidsri, Nattakan Kanana, Nattika Nimmano.

   Purpose: The study aimed to investigate in vitro anti-aging activities of 29 Dendrobium spp. and develop and characterize microemulsions (MEs) for topical application.
Methods: Antioxidant activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), H2O2 scavenging, and ferric reducing antioxidant power (FRAP) assays. The anti-collagenase (MMP-1 and MMP-2) and anti-elastase activities were also evaluated. Cytotoxicity and human intracellular reactive oxygen species (ROS) levels were determined using resazurin reduction and 2',7'-dichlorofluorescin diacetate (DCFDA) assays, respectively. D. kentrophyllum extract-loaded microemulsion (DKME) was then prepared and optimized. The stability of DKME was studied using a heating-cooling cycle.
Results: D. kentrophyllum appeared to be the best candidate anti-aging agent because of its antioxidant, anti-collagenase, and anti-elastase activities. The extract was safe for human skin cells at a concentration of 6.25-100 μg/mL. It also decreased the intracellular ROS-induced ultraviolet B (UVB) irradiation compared to that in the control. DKME comprising Tween 80:ethanol (5:1), water, and isononyl isononanoate showed a suitable appearance, droplet size, polydisperse index, zeta potential, pH, and viscosity. This formulation demonstrated desirable physical and chemical stability, with non-cytotoxic effects.
Conclusion: DKME is considered a promising anti-aging product. However, an in vivo study of this optimized formulation might be evaluated in further study for anti-aging purposes.

Keywords:  Dendrobium kentrophyllum; anti-aging activities; microemulsion; reactive oxygen species

DOI:  https://doi.org/10.2147/NSA.S508582
Free Radic Biol Med. 2025 Apr 01. pii: S0891-5849(25)00195-9. [Epub ahead of print]

Targeting LKB1-AMPK-SIRT1-induced autophagy and mitophagy pathways improves cerebrovascular homeostasis in APP/PS1 mice.

Yawen Li, Tongxing Wang, Hongrong Li, Yuning Jiang, Xiaogang Shen, Ning Kang, Zhifang Guo, Runtao Zhang, Xuan Lu, Tianyu Kang, Mengnan Li, Yunlong Hou, Yiling Wu.

   BACKGROUND: Alzheimer's disease (AD) is the most common and severe degenerative disorder of the central nervous system in the elderly, profoundly impacting patients' quality of life. However, effective therapeutic agents for AD are still lacking. Bazi Bushen (BZBS) is a traditional Chinese herbal compound with potential neuroprotective effects, yet its underlying mechanisms remain poorly understood.
METHODS: In this study, we utilized APP/PS1 transgenic mice to assess the therapeutic efficacy of BZBS. Initially, we evaluated the spatial learning and memory of the mice using the Barnes maze. The brain microcirculation was assessed through a small-animal ultrasound system, two-photon in vivo imaging, and micro-computed tomography angiography. Molecular, biochemical, and pathological analyses were conducted on brain tissues. Through network pharmacology, we identified potential intervention pathways and targets for BZBS in the treatment of AD, which we subsequently validated both in vivo and in vitro. Additionally, we employed molecular virtual docking screening and bio-layer interferometry to elucidate the direct interactions of ginsenoside Rg5 and ginsenoside Ro in BZBS with AMPK and LKB1 proteins.
RESULTS: The BZBS intervention significantly enhanced spatial learning and memory in APP/PS1 mice while decreasing Aβ deposition. Furthermore, BZBS protected cerebrovascular homeostasis and mitigated neuroinflammation, as evidenced by decreased blood-brain barrier permeability, increased expression of tight-junction proteins, and restored cerebral blood flow. Mechanistically, ginsenosides Rg5 and Ro in BZBS directly bind to AMPK and LKB1 proteins, activating the LKB1-AMPK-SIRT1 signaling pathway, promoting autophagy and mitochondrial autophagy, and alleviating oxidative stress damage in endothelial cells.
CONCLUSIONS: BZBS enhances autophagy-related activity, decreases Aβ deposition, and improves endothelial cell homeostasis through the activation of the LKB1-AMPK-SIRT1 signaling pathway, ultimately leading to improved cognitive function in mice with AD. This study highlights the importance of enhancing autophagic activity and maintaining cerebrovascular homeostasis in mitigating cognitive decline in AD, providing evidence and new insights into the application of compound medicines for treating age-related neurological disorders.

Keywords:  Alzheimer’s disease; Bazi Bushen; blood–brain barrier; ginsenosides; mitophagy

DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.03.045
J Cosmet Dermatol. 2025 Apr;24(4): e16664

In Vitro, Ex Vivo, Instrumental, and Clinical Assessment of a Novel Anti-aging Serum Targeting Oxidative Stress.

Sayantani Goswami, Jin Namkoong, Marwa El Hajoui, Ewelina Lesniak, Joanna Wu.

   BACKGROUND: Primarily driven by oxidative stress, aging results from the attrition of cells, aggravated by environmental stressors. Therefore, protection from oxidative stress is the main target of antiaging cosmetics.
AIMS: To evaluate the efficacy of a unique cosmetic serum combining five antioxidants and hyaluronic acid.
METHODS: The inactivation of reactive oxygen species by the serum was evaluated in-tubo. IL-1α release was evaluated using EpiDermTM skin models, while gene expression analysis and elastin fiber length were evaluated on human skin explants. Finally, the effect of twice daily serum application for 28 days was compared to those induced by a control serum, focusing on instrumental and assessor evaluations.
RESULTS: In-tubo, the serum reduces reactive oxygen species by 45.2%. A single topical application on EpiDermTM skin models limits UV-induced ROS-mediated IL-1α release. Compared to untreated explants, HB-EGF (heparin-binding epidermal growth factor) skin homeostasis marker expression increases by 22-fold with treatment. Additionally, the serum increases elastin fiber length by 40.2%. Clinically, twice daily application of the serum over a period of 7 days revealed significant improvements in clinical scoring of skin's wrinkle (-12.8%), smoothness (+12.5%), and radiance (+22.2%). The serum also leads to a rapid and long-lasting increase in skin hydration (30 min: +50.5%, 28 days: +19.9%) and reduced transepidermal water loss (30 min: -7.7%, 28 days: -8.7%). The serum is highly efficacious and well tolerated by the subjects.
CONCLUSION: The serum has antioxidant, soothing, photoprotective, and moisturizing properties that can be explained by the individual properties of its unique blend of actives.

Keywords:  aging; cosmetic; hydration; oxidative stress; skin

DOI:  https://doi.org/10.1111/jocd.16664