bims-caglex 2025-03-23 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2025–03–23
35 papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

Senescent cells as a target for anti-aging interventions: From senolytics to immune therapies.
Sex, senescence, senolytics, and cognition.
Senolytics Reduce Endothelial Cell DNA Damage and Telomere Dysfunction Despite Reductions in Telomere Length.
A Xanthine Derivative With Novel Heat Shock Protein 90-Alpha Inhibitory and Senolytic Properties.
Determination of health status during aging using bending and pumping rates at various survival rates in Caenorhabditis elegans.
Plant polysaccharides with anti-aging effects and mechanism in evaluation model Caenorhabditis elegans.
[Research progress of the anti-aging effect mechanism of acupuncture and moxibustion in recent ten years].
Nanovaccine loaded with seno-antigen target senescent cells to improve metabolic disorders of adipose tissue and cardiac dysfunction.
Impact of a water-soluble soy extract on inflammation and gut microbiota in physiologically aged mice.
Inhibition of the metalloprotease ADAM19 as a novel senomorphic strategy to ameliorate gut permeability and senescence markers by modulating senescence-associated secretory phenotype (SASP).
Glutaminase-responsive nano-carrier for precise rejuvenation of senescent cells by restoring autophagy in chronic kidney disease treatment.
Evaluation of Anti-aging Agents Using the D-Galactose-Induced Accelerated Aging Model.
Salutary effects of transdermal curcumin on multiple indices of health span in rodent models of normal aging and hypertension.
Exploration of the mechanism and therapy of ovarian aging by targeting cellular senescence.
Prevention of cardiovascular disease for healthy aging and longevity: A new scoring system and related "mechanisms-hallmarks-biomarkers".
Polyphenol extracts from rambutan peel promote longevity via the attenuation of the Toll/Imd pathway.
Targeted Partial Reprogramming as a Novel Therapeutic Strategy for Age-Related Decline.
Caloric restriction reprograms adipose tissues in rhesus monkeys.
The role of retinal pigment epithelial senescence and the potential of senotherapeutics in age-related macular degeneration.
Germline expression of Imp-L2 in Drosophila females enhances reproductive activity and longevity.
The Codonopsis pilosula water extract improves testicular inflammatory aging in D-galactose induced aging mice by modulating the CLEC7A/inflammasome pathway.
Effects of a natural ingredients-based intervention targeting the hallmarks of aging on epigenetic clocks, physical function, and body composition: a single-arm clinical trial.
Water extract of Humulus japonicus improves age‑related cognitive decline by inhibiting acetylcholinesterase activity and the acetylcholine signaling pathway.
Nanoparticle-Driven Skeletal Muscle Repair and Regeneration Through Macrophage-Muscle Stem Cell Interaction.
How to promote healthy aging across the life cycle.
The cyclic metabolic switching theory of intermittent fasting.
Noncoding RNAs evolutionarily extend animal lifespan.
Astaxanthin: a nature's versatile compound utilized for diverse applications and its therapeutic effects.
Circuit training intervention for cognitive function, gut microbiota, and aging control: study protocol for a longitudinal, open-label randomized controlled trial.
Transgenerational inheritance of mitochondrial hormetic oxidative stress mediated by histone H3K4me3 and H3K27me3 modifications.
Hybrid Fillers Personal Experience of Premixing Calcium Hydroxylapatite and Hyaluronic Acid for Natural Face Reshaping.
Adherence to the cMIND and AIDD diets and their associations with anxiety in older adults in China.
Correction to: Yo-Yo Dieting Delays Male Drosophila melanogaster Aging Through Enhanced Mitochondrial Function, Relative to Sustained High-Calorie Diet Feeding.
PoWeR elicits intracellular signaling, mitochondrial adaptations, and hypertrophy in multiple muscles consistent with endurance and resistance exercise training.
Elucidating the mechanisms of Shenwu Capsule in improving the cognitive decline in aging based on the UPLC-Q-TOF-MS, network pharmacology, and experimental validation.

J Transl Int Med. 2025 Feb;13(1): 33-47

Senescent cells as a target for anti-aging interventions: From senolytics to immune therapies.

Tianlu Esther Fu, Zhongjun Zhou.

  Aging and age-related diseases are major drivers of multimorbidity and mortality worldwide. Cellular senescence is a hallmark of aging. The accumulation of senescent cells is causally associated with pathogenesis of various age-associated disorders. Due to their promise for alleviating age-related disorders and extending healthspan, therapeutic strategies targeting senescent cells (senotherapies) as a means to combat aging have received much attention over the past decade. Among the conventionally used approaches, one is the usage of small-molecule compounds to specifically exhibit cytotoxicity toward senescent cells or inhibit deleterious effects of the senescence-associated secretory phenotype (SASP). Alternatively, there are immunotherapies directed at surface antigens specifically upregulated in senescent cells (seno-antigens), including chimeric antigen receptor (CAR) therapies and senolytic vaccines. This review gives an update of the current status in the discovery and development of senolytic therapies, and their translational progress from preclinical to clinical trials. We highlight the current challenges faced by senotherapeutic development in the context of senescence heterogeneity, with the aim of offering novel perspectives for future anti-aging interventions aimed at enhancing healthy longevity.

Keywords:  age-related diseases; cellular senescence; immune therapy; seno-antigens; small molecules

DOI:  https://doi.org/10.1515/jtim-2025-0005
Front Aging Neurosci. 2025 ;17 1555872

Sex, senescence, senolytics, and cognition.

Thomas C Foster, Ashok Kumar.

  This review focuses on sexual dimorphism in cellular senescence and senolytic treatment in relation to brain health and age-related cognitive decline. The stressors of aging, DNA damage, inflammation, and oxidative stress induce cell senescence, a hallmark of aging. Senescent cells change their function and molecular profile and are primed to release pro-inflammatory cytokines. The functional changes include the activation of cell signals to prevent cell death. The release of pro-inflammatory cytokines from peripheral senescent cells during middle age induces senescence of neighbor cells and heightens the level of systemic inflammation, contributing to neuroinflammation. In response to neuroinflammation and oxidative stress, some neurons alter their physiology, decreasing neuronal excitability and synaptic transmission. Senescent neurophysiology is protective against cell death due to excitotoxicity, at the expense of a loss of normal cell function, contributing to age-related cognitive decline. The level of peripheral cell senescence and systemic inflammation may underlie sexual dimorphism in the prevalence, symptoms, and pathogenesis of age-related diseases, including neurodegenerative diseases. Sex differences have been observed for senescence of astrocytes, microglia, and peripheral cells, including those involved in innate and adaptive immune responses. Interventions that remove senescent cells, such as senolytic drugs, can reduce or ameliorate some of the aging-related loss of function. Similarities and differences in senolytic responses of males and females depend on the system examined, the treatment regimen, the level of senescent cell burden, and the age when treatment is initiated. Estrogen impacts several of these factors and influences the transcription of genes promoting growth, proliferation, and cell survival programs in a manner opposite that of senolytic drugs. In addition, estrogen has anti-aging effects that are independent of cell senescence, including rapidly modifying senescent neurophysiology. Thus, it is important to recognize that, in addition to sex differences in cell senescence, there are other sexually dimorphic mechanisms that contribute to the aging process. The results indicate that senolytics interact with fundamental biology, including sex hormones.

Keywords:  aging; cellular senescence; senolytic treatment; sex differences; sex hormone

DOI:  https://doi.org/10.3389/fnagi.2025.1555872
Aging Biol. 2023 ;pii: e20230007. [Epub ahead of print]1

Senolytics Reduce Endothelial Cell DNA Damage and Telomere Dysfunction Despite Reductions in Telomere Length.

Samuel I Bloom, Eric Tuday, Torikul Islam, Venkateswara R Gogulamudi, Lisa A Lesniewski, Anthony J Donato.

Aging results in cellular damage that can induce cell cycle arrest known as cellular senescence. Endothelial cells are one of the first cell types to become senescent in advancing age and contribute to age-related cardiovascular diseases. Drugs known as senolytics reduce endothelial cell senescence in cell culture. From a translational perspective, a key question is whether this occurs in vivo and if remaining cells appear healthier and display fewer hallmarks of cellular aging. In this study, we treated old mice with the senolytic cocktail dasatinib and quercetin (D+Q) or a vehicle control. In 24-month-old mice, D+Q treatment reduced p21 gene expression in carotid artery endothelial cells, indicative of reductions in senescence. In lung endothelial cells, we examined DNA damage, telomere dysfunction (DNA damage signaling at telomeres), and telomere length, which are hallmarks of aging associated with senescence and other deleterious effects on cellular function. D+Q treatment resulted in fewer endothelial cells with DNA damage and dysfunctional telomeres. Surprisingly, D+Q reduced endothelial cell telomere length, yet this did not result in critically short telomeres and thus telomere dysfunction. Mice have longer telomeres than humans; therefore, future studies on the effect of senolytics on telomere length are warranted. Collectively, this study provides important evidence on the effect of senolytics, including that they clear senescent endothelial cells in vivo, which reduces DNA damage and telomere dysfunction. These data indicate that the clearing of senescent endothelial cells in old age leaves behind a population of cells that exhibit fewer hallmarks of vascular aging.

DOI: https://doi.org/10.59368/agingbio.20230007
Aging Cell. 2025 Mar 17. e70047

A Xanthine Derivative With Novel Heat Shock Protein 90-Alpha Inhibitory and Senolytic Properties.

Sandra Atlante, Luca Cis, Davide Pirolli, Michela Gottardi Zamperla, Veronica Barbi, Antonello Mai, Clemens Zwergel, Serena Marcozzi, Maria Elisa Giuliani, Giorgia Bigossi, Giovanni Lai, Fiorenza Orlando, Robertina Giacconi, Fabrizia Lattanzio, Giulia Matacchione, Chiara Giordani, Massimo Bracci, Fabiola Olivieri, Federico Boschi, Paola Tabarelli De Fatis, Giovanni Battista Ivaldi, Marco Malavolta, Antonella Farsetti, Maria Cristina De Rosa, Carlo Gaetano.

  The accumulation of senescent cells contributes to aging and related diseases; therefore, discovering safe senolytic agents-compounds that selectively eliminate senescent cells-is a critical priority. Heat shock protein 90 (HSP90) inhibitors (HSP90i), traditionally investigated for cancer treatment, have shown potential as senolytic agents. However, inhibitors face formulation, toxicity, and cost challenges. To overcome these limitations, we employed a virtual screening approach combining structure-based prefiltering with a ligand-based pharmacophore model to identify novel, potentially safe HSP90 alpha isoform inhibitors exhibiting senolytic properties. This strategy identified 14 candidate molecules evaluated for senolytic activity in primary human fetal pulmonary fibroblasts. Four compounds exhibited significant HSP90i and senolytic activity, including two novel compounds, namely K4 and K5. The latter, 1-benzyl-3-(2-methylphenyl)-3,7-dihydro-1H-purine-2,6-dione, structurally related to the xanthinic family, emerged as a promising, well-tolerated senolytic agent. K5 demonstrated senolytic activity across various cellular senescence models, including human fibroblasts, mesenchymal stem cells, and breast cancer cells. It was also effective in vivo, extending lifespan in Drosophila and reducing senescence markers in geriatric mice. Additionally, the xanthinic nature of K5 implicates a multimodal action, now including the inhibition of HSP90α, that might enhance its efficacy and selectivity towards senescent cells, Senolytic index SI > 1320 for IMR90 cells, and SI > 770 for WI38 cells, underscoring its therapeutic potential. These findings advance senolytic therapy research, opening new avenues for safer interventions to combat age-related inflammaging and diseases, including cancer, and possibly extend a healthy lifespan.

Keywords:   drosophila ; HSP90α inhibitors; aging; senescence; senolytics; xanthine

DOI:  https://doi.org/10.1111/acel.70047
Sci Rep. 2025 Mar 17. 15(1): 9057

Determination of health status during aging using bending and pumping rates at various survival rates in Caenorhabditis elegans.

Junhyo Cho, Jiakai Lu, Daeyoung Kim, Yeonhwa Park.

  Alongside recognizing the importance of extending lifespan, an emerging focus has appeared on improving health in longevity, defined as healthspan. Aging is a process for all animal species; however, due to the time limitation in aging studies, Caenorhabditis elegans is an established model used for studying aging. In the current study, we evaluated various markers of muscle functions and determined that bending or pharyngeal pumping rate can represent worms' healthiness. A new concept named 'dynamic-scaled value' was developed, rescaling health markers to the corresponding markers in the control group at the same survival rate. Using these dynamic-scaled values of bending or pumping rates, we determined the health status of various treatments, including whether health improvement over aging depended on lifespan extension. Co-treatment of cranberry juice with Lactobacillus plantarum significantly improved health status during the mid-late life stage, while cranberry juice alone did not improve compared to the control. The dynamic-scaled value can be used as a complementary indicator to the quality-adjusted values to determine the health status. In addition, the dynamic-scaled values would allow us to compare results from others based on adjustments using their respective controls and relatively simple measurements to obtain the results.

Keywords:   C. elegans ; Lactobacillus plantarum ; Aging; Cranberry; Healthy aging

DOI:  https://doi.org/10.1038/s41598-025-93876-8
Int J Biol Macromol. 2025 Mar 18. pii: S0141-8130(25)02820-X. [Epub ahead of print] 142268

Plant polysaccharides with anti-aging effects and mechanism in evaluation model Caenorhabditis elegans.

Jian Ji, Honglin Yan, Yongli Ye, Zhongjia Huang, Yuting Wang, Jiadi Sun, Lina Sheng, Yinzhi Zhang, Xiulan Sun.

  Aging in human evolution leads to function decline and immune weakening, causing severe problems. Plant polysaccharides, as a key source of dietary fiber, play vital roles in enhancing intestinal health, regulating blood glucose, lowering cholesterol, and offer promising strategies for aging prevention. This review begins by examining the characteristics and applications of polysaccharides and elucidates the mechanisms of anti-aging effect of plant polysaccharides. It focuses on nematodes as an ideal anti - aging model, expounding their aging indicator evaluation methods, highlighting key pathways and molecules for aging inhibition, and elaborating on related plant polysaccharides. As polysaccharide anti - aging research mainly focuses on plants, this study aims to support their use against aging. C. elegans provides new anti - aging insights, but limited understanding of plant polysaccharide structure challenges structure - activity analysis. The review presents C. elegans - based strategies and plant polysaccharide challenges for further research. In summary, this review proposes novel strategies developed by Caenorhabditis elegans in anti-aging research as well as the challenges facing plant polysaccharides, providing insights for further research on anti-aging plant polysaccharides.

Keywords:  Anti-aging; Caenorhabditis elegans; Pathway; Plant polysaccharides

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.142268
Zhen Ci Yan Jiu. 2025 Mar 25. pii: 1000-0607(2025)03-0349-08. [Epub ahead of print]50(3): 349-356

[Research progress of the anti-aging effect mechanism of acupuncture and moxibustion in recent ten years].

Tze-Jieh Wee, Xue-Kun Liu, Li Hu.

  The aging of the population is one of the most concerns in the medical circle. Exploring the safe and effective anti-aging protocol is important in the study. The paper summarized the relevant articles for the anti-aging effect mechanism of acupuncture and moxibustion in recent 10 years from 9 aspects such as resisting oxidation and free radical damage, and regulating body immunity, neuroendocrine function, cell autophagy, aging-related gene expression, the deacetylase (Sirtuins) family, telomere with telomerase, epigenetic and iron metabolism. It is pointed out that acupuncture-moxibustion refers to the holistic therapy for anti-aging, characterized as multiple targets, multiple channels and full dimensions. The multidisciplinary cross-over study should be conduced on the basis of the dual regulatory effect of acupuncture and moxibustion, combined with modern life science and artificial intelligence technology, which is significant to reveal the scientific mechanism of acupuncture and moxibustion for anti-aging.

Keywords:  Acupuncture and moxibustion; Anti-aging; Mechanism of aging

DOI:  https://doi.org/10.13702/j.1000-0607.20230910
Hum Vaccin Immunother. 2025 Dec;21(1): 2479229

Nanovaccine loaded with seno-antigen target senescent cells to improve metabolic disorders of adipose tissue and cardiac dysfunction.

Kexin Zhang, Qiliang Yin, Yucen Ma, Mengyu Cao, Lingwei Li, Xinliang Jin, Jiyan Leng.

  The buildup of senescent cells exacerbates metabolic disorders in adipose tissue and contributes to aging-related cardiac dysfunction. Targeted clearance of senescent cells can markedly ameliorate these aging-related diseases. Here, we developed a novel nanovaccine (GK-NaV) loaded with seno-antigen that is self-assembled from the fusion of cationic protein (K36) and seno-antigen peptide (Gpnmb). The GK-NaV could be highly engulfed by bone marrow-derived dendritic cells (BMDCs) and efficiently present antigens on the cellular surface, thereby promoting DCs maturation and activation of CD8+T cells in vitro. Following subcutaneous immunization, GK-NaV not only exhibited a noticeable antigen depot effect but also markedly activated specific cellular immune responses, enhancing the immunoreactivity and cytotoxic effects of CD8+T cells. Consequently, the targeted anti-aging immunity triggered by GK-NaV demonstrated the ability to selectively eliminate senescent adipocytes and cardiomyocytes in high-fat diet (HFD)-induced progeroid mice, leading to a significant improvement in age-related metabolic disorders in adipose tissue and cardiac dysfunction. Hence, our findings indicate that immunization with GK-NaV targeting seno-antigens may represent a promising strategy for novel senolytic therapies.

Keywords:  Nanovaccine; cardiac dysfunction; metabolic disorders; senescent cells; seno-antigen

DOI:  https://doi.org/10.1080/21645515.2025.2479229
Biosci Biotechnol Biochem. 2025 Mar 17. pii: zbaf032. [Epub ahead of print]

Impact of a water-soluble soy extract on inflammation and gut microbiota in physiologically aged mice.

Kenji Watanabe, Yuka Kamei, Miki Igarashi, Shuichi Shibuya, Takahiko Shimizu, Ikuo Kimura, Mitsuo Maruyama.

  Soy isoflavones are involved deeply in our diet as beneficial to the health. It is known to have anti-inflammatory and antioxidant effects and also to be effective in alleviating various lifestyle diseases, as well as the maintenance of endocrine function especially with age-related diseases such as osteoporosis. Here we investigated the impact of age-dependent changes with the intestinal microbiota in physiologically aged C57BL/6 N by free drinking water with soluble soybean-derived isoflavone glycosides (SIFs) for 4 weeks. Consequently, Akkermansia muciniphila (A. muciniphila) species represented age-dependent increase with SIF treatment, subsequently, generally age-dependent decreased goblet cells are retained in the large intestine. These results invoke that SIF plays a beneficial role on intestinal barrier function to maintain the large intestine homeostasis. Interestingly, we also revealed that SIF had an alleviating effect on age-dependent bone loss. Taken together, SIF has fruitful effect on the intestinal environment and maintenance of homeostasis in physiological aging.

Keywords:  cellular senescence; microbiome; murine intestine; short chain fatty acids; soy isoflavones

DOI:  https://doi.org/10.1093/bbb/zbaf032
Aging (Albany NY). 2025 Mar 20. null

Inhibition of the metalloprotease ADAM19 as a novel senomorphic strategy to ameliorate gut permeability and senescence markers by modulating senescence-associated secretory phenotype (SASP).

Sudipta Bar, Tyler A U Hilsabeck, Blaine Pattavina, José Alberto López-Domínguez, Nathan Basisty, Joanna Bons, Mark Watson, Birgit Schilling, Judith Campisi, Pankaj Kapahi, Amit Sharma.

  Accumulation of DNA damage can accelerate aging through cellular senescence. Previously, we established a Drosophila model to investigate the effects of radiation-induced DNA damage on the intestine. In this model, we examined irradiation-responsive senescence in the fly intestine. Through an unbiased genome-wide association study (GWAS) utilizing 156 strains from the Drosophila Genetic Reference Panel (DGRP), we identified meltrin (the drosophila orthologue of mammalian ADAM19) as a potential modulator of the senescence-associated secretory phenotype (SASP). Knockdown of meltrin resulted in reduced gut permeability, DNA damage, and expression of the senescence marker β-galactosidase (SA-β-gal) in the fly gut following irradiation. Additionally, inhibition of ADAM19 in mice using batimastat-94 reduced gut permeability and inflammation in the gut. Our findings extend to human primary fibroblasts, where ADAM19 knockdown or pharmacological inhibition decreased expression of specific SASP factors and SA-β-gal. Furthermore, proteomics analysis of the secretory factor of senescent cells revealed a significant decrease in SASP factors associated with the ADAM19 cleavage site. These data suggest that ADAM19 inhibition could represent a novel senomorphic strategy.

Keywords:  SASP; aging; drosophila; senescence

DOI:  https://doi.org/10.18632/aging.206224
Int J Pharm. 2025 Mar 13. pii: S0378-5173(25)00305-9. [Epub ahead of print]674 125469

Glutaminase-responsive nano-carrier for precise rejuvenation of senescent cells by restoring autophagy in chronic kidney disease treatment.

Wentao Zhou, Caini Yu, Tingting Meng, Qi Jiang, Fangying Yu, Hong Yuan.

  Cellular senescence disrupts tissue homeostasis and diminishes physiological integrity, leading to the accumulation of senescent cells (SCs) in multiple senescence-associated diseases such as chronic kidney disease (CKD). Treatment of SCs has been approved to be a feasible approach to these diseases. However, curing SCs in different cell types remains challenging. In this study, we leveraged the high expression of glutaminase (GLS) in SCs to develop a drug delivery system utilizing γ-poly glutamic acid (γ-PGA) conjugated with octadecylamine (ODA) to encapsulate rapamycin (RP), resulting in a GLS-responsive drug delivery system, designated as RPPO. In a model of drug induced senescence, the γ-PGA component of RPPO was degraded by cellular GLS, facilitating the release of encapsulated RP and rejuvenating SCs by restoring the autophagic capacity. Additionally, in a model of CKD in mice, RPPO enhanced recovery by rejuvenating SCs, reducing fibrosis, and alleviating inflammation. Thus, this senescent cell-responsive drug delivery system presents a novel approach for the treatment of CKD.

Keywords:  Cellular senescence; Chronic kidney disease; Glutaminase; Rapamycin; γ-Poly glutamic acid

DOI:  https://doi.org/10.1016/j.ijpharm.2025.125469
Methods Mol Biol. 2025 Mar 20.

Evaluation of Anti-aging Agents Using the D-Galactose-Induced Accelerated Aging Model.

Serdar Bora Bayraktaroğlu, Raife Dilek Turan, Neslihan Pakize Taşlı, Fikrettin Şahin.

  The aging population is rapidly increasing, emphasizing the importance of understanding aging mechanisms and developing effective anti-aging therapies. This chapter investigates the efficacy of novel anti-aging agents, including exosomes and boron compounds, using the D-galactose-induced accelerated aging model. Both in vitro (skin organoid models) and in vivo (rat models) systems are employed to explore cellular, molecular, and histological changes. This comprehensive analysis provides critical insights into the potential of these agents in reversing age-associated pathologies.

Keywords:  Accelerated model; Aging aging; Anti-aging applications; D-Galactose; Reactive oxygen species

DOI:  https://doi.org/10.1007/7651_2025_609
Geroscience. 2025 Mar 15.

Salutary effects of transdermal curcumin on multiple indices of health span in rodent models of normal aging and hypertension.

Kai Mao, Ruixuan Wang, Kateryna Karpoff, Daniel Kerr, Probal Banerjee, Joel M Friedman, Derek M Huffman.

  Geroscience has helped to usher in a new and exciting era of aging drug development and evaluation of novel and repurposed agents, as well as natural compounds purported to target one or more aging hallmarks. Among the latter, curcumin has long been pursued as a promising strategy but has failed to provide convincing evidence in human trials. Oral intake is the typical route of administration tested for the vast majority of gerotherapeutic candidates, including curcumin, but efficacy is dependent upon good oral bioavailability and pharmacokinetics. However, unlike FDA-approved oral medications, many natural compounds, such as curcumin, have poor oral bioavailability, which may explain their limited success in translation. To overcome these inherent limitations, we tested a novel solvent-based formulation of concentrated curcumin (VASCEPTOR®), developed for effective skin penetration and delivery of high amounts of bioactive curcuminoids directly to the circulation on aging and age-related conditions. We demonstrate that short-term topical treatment (7.5 mg per dose) with VASCEPTOR® twice per week can improve both vascular health in a rat model of hypertension, while a late-life intervention in aged mice improves multiple indices of health span, including improved exercise tolerance, motor coordination, diastolic function (p < 0.05), a reduction in frailty status (p < 0.05) and expression of some age-related markers in tissues, particular heart and kidney. Thus, these data suggest that the therapeutic potential of curcumin can potentially be dramatically enhanced by topical delivery and, along with other promising candidates, should be prioritized for further development, testing and deployment to potentially target some manifestations of aging in humans.

Keywords:  Aging; Curcumin; Frailty; Hypertension; Inflammation

DOI:  https://doi.org/10.1007/s11357-025-01607-8
Life Med. 2025 Feb;4(1): lnaf004

Exploration of the mechanism and therapy of ovarian aging by targeting cellular senescence.

Weicheng Tang, Kaichen Wang, Yourong Feng, Kuan-Hao Tsui, Keshav K Singh, Michael B Stout, Shixuan Wang, Meng Wu.

  The ovary is a crucial gonadal organ that supports female reproductive and endocrine functions. Ovarian aging can result in decreased fertility and dysfunction across multiple organs. Research has demonstrated that cellular senescence in various cell types within the ovary can trigger a decline in ovarian function through distinct stress responses, resulting in ovarian aging. This review explores how cellular senescence may contribute to ovarian aging and reproductive failure. Additionally, we discuss the factors that cause ovarian cellular senescence, including the accumulation of advanced glycation end products, oxidative stress, mitochondrial dysfunction, DNA damage, telomere shortening, and exposure to chemotherapy. Furthermore, we discuss senescence in six distinct cell types, including oocytes, granulosa cells, ovarian theca cells, immune cells, ovarian surface epithelium, and ovarian endothelial cells, inside the ovary and explore their contribution to the accelerated ovarian aging. Lastly, we describe potential senotherapeutics for the treatment of ovarian aging and offer novel strategies for ovarian longevity.

Keywords:  cellular senescence; granulosa cells; oocyte; ovarian aging; senotherapy

DOI:  https://doi.org/10.1093/lifemedi/lnaf004
Ageing Res Rev. 2025 Mar 15. pii: S1568-1637(25)00073-X. [Epub ahead of print]107 102727

Prevention of cardiovascular disease for healthy aging and longevity: A new scoring system and related "mechanisms-hallmarks-biomarkers".

Chunsong Hu.

  Healthy "environment-sleep-emotion-exercise-diet" intervention [E(e)SEEDi] lifestyle can improve the quality of life, prolong aging and promote longevity due to improvement of human immunity and prevention of cardiovascular diseases (CVD). Here, the author reviewed the associations between these core elements with CVD and cardiovascular aging, and developed a new scoring system based on the healthy E(e)SEEDi lifestyle for prediction and evaluation of life expectancy. These core factors are assigned 20 points each (120 points in total), and a higher score predicts healthier aging and longevity. The E(e)SEEDi represents "a tree of life" bearing the fruits of longevity as well as "a rocket of anti-ageing" carrying people around the world on a journey of longevity. In conclusion, the E(e)SEEDi can delay aging and increase the life expectancy due to the role of a series of cellular and molecular "mechanisms-hallmarks-biomarkers". It's believed that the novel scoring system has a huge potential and beautiful prospects.

Keywords:  Aging; Cardiovascular disease; E(e)SEEDi lifestyle; Longevity; Mechanisms-hallmarks-biomarkers

DOI:  https://doi.org/10.1016/j.arr.2025.102727
Food Funct. 2025 Mar 17.

Polyphenol extracts from rambutan peel promote longevity via the attenuation of the Toll/Imd pathway.

Jian-Cong Huang, Xue-Kun Pan, Shun-Cai Li, Wen-Hui Zeng, Yu-Jie Zhong, Hong-Yu Pan, Yong-Liang Zhuang.

Rambutan peel is rich in polyphenols such as ellagic acid, corilagin, geraniin, quercetin, and rutin, which contribute to its diverse health benefits, including antioxidant, antimicrobial, antiviral, anti-inflammatory, hypoglycemic, and potential anticancer properties. The polyphenols present in the rambutan peel demonstrate potential for delaying cellular aging by mitigating oxidative stress within cells. Moreover, no study has systematically explored the anti-aging effects and the underlying mechanisms of polyphenols derived from rambutan peel. Drosophila melanogaster has often been used in aging studies to reveal the mechanisms of aging onset and development. Using Drosophila melanogaster as an in vivo aging model, the aim of the present study was to probe whether rambutan peel polyphenol extracts (RPPEs) exert a lifespan extending effect in vivo and to gain insights into the mechanism of action. Results highlighted that the optimized concentration of RPPEs for the anti-aging treatment in Drosophila melanogaster was 5 mg mL-1. In addition, RPPEs extended the lifespan of Drosophila melanogaster in a manner that was related to the dose and gender. Meanwhile, RPPEs improved the climbing ability and sleep and maintained the antioxidant capacity of aged Drosophila. RPPEs also ameliorated intestinal barrier damage in aging Drosophila. Transcriptome sequencing analysis showed that RPPEs extended the lifespan of Drosophila by down-regulating the Toll/IMD signaling pathway.

DOI: https://doi.org/10.1039/d4fo06353h
Ageing Res Rev. 2025 Mar 15. pii: S1568-1637(25)00077-7. [Epub ahead of print] 102731

Targeted Partial Reprogramming as a Novel Therapeutic Strategy for Age-Related Decline.

Eli Adashi, Max Rose.

Cellular reprogramming has emerged as a promising strategy for the amelioration of age-associated cellular phenotypes. In-vivo reprogramming approaches, however, have been limited by a lack of specificity and oncogenic risk. Recent breakthroughs have addressed these limitations, constituting a significant progression toward the development of safe and effective therapeutics for age-related pathologies.

DOI: https://doi.org/10.1016/j.arr.2025.102731
bioRxiv. 2025 Mar 05. pii: 2025.03.03.641286. [Epub ahead of print]

Caloric restriction reprograms adipose tissues in rhesus monkeys.

Josef P Clark, Timothy W Rhoads, Sean J McIlwain, Michael A Polewski, Derek Pavelec, Ricki J Colman, Rozalyn M Anderson.

Caloric restriction (CR) is a dietary intervention that delays the onset of age-related diseases and enhances survival in diverse organisms, and although changes in adipose tissues have been implicated in the beneficial effects of CR the molecular details are unknown. Here we show shared and depot-specific adaptations to life-long CR in subcutaneous and visceral adipose depots taken from advanced age male rhesus monkeys. Differential gene expression and pathway analysis identified key differences between the depots in metabolic, immune, and inflammatory pathways. In response to CR, RNA processing and proteostasis-related pathways were enriched in both depots but changes in metabolic, growth, and inflammatory pathways were depot-specific. Commonalities and differences that distinguish adipose depots are shared among monkeys and humans and the response to CR is highly conserved. These data reveal depot-specificity in adipose tissue adaptation that likely reflects differences in function and contribution to age-related disease vulnerability.

DOI: https://doi.org/10.1101/2025.03.03.641286
Surv Ophthalmol. 2025 Mar 13. pii: S0039-6257(25)00053-0. [Epub ahead of print]

The role of retinal pigment epithelial senescence and the potential of senotherapeutics in age-related macular degeneration.

Yingying Chen, Feipeng Jiang, Yue Zeng, Meixia Zhang.

  Age-related macular degeneration (AMD) is a leading cause of visual impairment in the aging population. Evidence showing the presence of cellular senescence in retinal pigment epithelium (RPE) of patients with AMD is growing. Senescent RPE play a pivotal role in its pathogenesis. The senescent RPE suffers from structural and functional alterations and disruption of the surrounding microenvironment due to the development of the senescence-associated secretory phenotype, which contributes to metabolic dysfunctions and inflammatory responses in the retina. Senotherapeutics, including senolytics, senomorphics and others, are novel treatments targeting senescent cells and are promising treatments for AMD. As senotherapeutic targets are being developed, it is promising that the burden of AMD could be decreased.

Keywords:  Age-related macular degeneration; Retinal pigment epithelium; Senescence; Senolytics; Senotherapeutics

DOI:  https://doi.org/10.1016/j.survophthal.2025.03.004
Anim Cells Syst (Seoul). 2025 ;29(1): 31-40

Germline expression of Imp-L2 in Drosophila females enhances reproductive activity and longevity.

Sujin Noh, Sungjoon Na, Xinge Song, Seogang Hyun.

  The Imaginal morphogenesis protein-Late 2 (Imp-L2) in Drosophila is recognized as a functional homolog of the insulin-like growth factor (IGF) binding protein family. In this study, we report that Imp-L2 expression in germline cells during oogenesis simultaneously enhances both fecundity and lifespan in female Drosophila. Loss of Imp-L2, either through knockout or germline-specific knockdown, resulted in decreased reproductive activity, as evidenced by reduced ovary size and fecundity, along with a higher proportion of infertile flies. Conversely, overexpression of Imp-L2 specifically in germline cells enhanced reproductive activity. Imp-L2 appears to regulate germline stem cell proliferation and differentiation independently of IGF signaling. Interestingly, germline-specific knockdown of Imp-L2 shortened the lifespan of female flies, whereas its overexpression extended it. Thus, Imp-L2 expression in the germline promotes both reproductive activity and longevity, presenting an exception to the typical trade-off between reproduction and lifespan.

Keywords:  Drosophila; Imp-L2; Insulin-like growth factor binding protein; lifespan; reproductive aging

DOI:  https://doi.org/10.1080/19768354.2025.2480150
J Ethnopharmacol. 2025 Mar 18. pii: S0378-8741(25)00329-0. [Epub ahead of print] 119645

The Codonopsis pilosula water extract improves testicular inflammatory aging in D-galactose induced aging mice by modulating the CLEC7A/inflammasome pathway.

Jing Wang, Xuechan Li, Caihong Li, Lijun Liu, Zhenjuan Wang, Juan Feng.

   AIM OF THE STUDY: Aging-induced testicular inflammation impairs male fertility. The purpose of this study was to investigate the effectiveness and mechanism of C. pilosula water extract (CPWE) in preventing testicular inflammation in D-galactose-induced aging mice.
MATERIALS AND METHODS: The "The Plant List" database (www.theplantlist.org) provided verified plant taxonomy. D-galactose was intraperitoneally injected to induce an aging mice model, with high, medium, and low dosages of CPWE used as pharmacological interventions. The concentrations of superoxide dismutase (SOD), malondialdehyde (MDA), testosterone and in mouse serum or testicle samples after CPWE treatment were quantified using biochemical method. Hematoxylin and eosin (HE) staining was employed to assess the morphological features of testicular tissues, whereas immunohistochemical (IHC) analysis and enzyme-linked immunosorbent assay (ELISA) were conducted to evaluate the presence and levels of inflammatory cytokines interleukin-6 (IL-6) and interleukin-1β (IL-1β) within testicular samples of mice. Differentially expressed genes were identified using transcriptome sequencing; the genes and pathways regulated by CPWE, as well as immune cell infiltration, were examined using bioinformatics analysis. The expression of target gene and pathway-related protein was confirmed using real-time quantitative PCR and Western blotting.
RESULTS: Treatment with CPWE alleviated the pathological alterations in the testicular tissues of aged mice, increased the concentrations of SOD and testosterone in the serum, and decreased the levels of MDA, IL-6 and IL-1β in the testes. The expression of C-C motif chemokine ligand 21a (Ccl21a) and C-C motif chemokine ligand 27b (Ccl27b) genes was downregulated after treatment with CPWE. The protein levels associated with the C-type lectin domain family 7, member A (CLEC7A)/inflammasome signaling pathway, including IL-1β, Caspase 8 (CASP8), and nuclear factor-kappa B (NF-κB), were found to be downregulated after treatment with CPWE. T cells, B cells, and macrophages showed a strong association with aging and the modulatory effects of CPWE.
CONCLUSIONS: The results indicate that CPWE regulates the CLEC7A/inflammasome pathway, thereby inhibiting inflammasomes activation and reducing the expressions of proinflammatory cytokines such as IL-6 and IL-1β, as well as chemokines such as Ccl21a and Ccl27b, providing substantial protection against age-related testicular inflammatory injury.

Keywords:  Aging; CLEC7A/inflammasome pathway; Codonopsis pilosula; D-galactose; Testicular inflammation

DOI:  https://doi.org/10.1016/j.jep.2025.119645
Aging (Albany NY). 2025 Mar 14. null

Effects of a natural ingredients-based intervention targeting the hallmarks of aging on epigenetic clocks, physical function, and body composition: a single-arm clinical trial.

Natalia Carreras-Gallo, Rita Dargham, Shealee P Thorpe, Steve Warren, Tavis L Mendez, Ryan Smith, Greg Macpherson, Varun B Dwaraka.

  Aging interventions have progressed in recent years due to the growing curiosity about how lifestyle impacts longevity. This study assessed the effects of SRW Laboratories' Cel System nutraceutical range on epigenetic methylation patterns, inflammation, physical performance, body composition, and epigenetic biomarkers of aging. A 1-year study was conducted with 51 individuals, collecting data at baseline, 3 months, 6 months, and 12 months. Participants were encouraged to walk 10 minutes and practice 5 minutes of mindfulness daily. Significant improvements in muscle strength, body function, and body composition metrics were observed. Epigenetic clock analysis showed a decrease in biological age with significant reductions in stem cell division rates. Immune cell subset analysis indicated significant changes, with increases in eosinophils and CD8T cells and decreases in B memory, CD4T memory, and T-regulatory cells. Predicted epigenetic biomarker proxies (EBPs) showed significant changes in retinol/TTHY, a regulator of cell growth, proliferation, and differentiation, and deoxycholic acid glucuronide levels, a metabolite of deoxycholic acid generated in the liver. Gene ontology analysis revealed significant CpG methylation changes in genes involved in critical biological processes related to aging, such as oxidative stress-induced premature senescence, pyrimidine deoxyribonucleotide metabolic process, TRAIL binding, hyaluronan biosynthetic process, neurotransmitter loading into synaptic vesicles, pore complex assembly, collagen biosynthetic process, protein phosphatase 2A binding activity, and activation of transcription factor binding. Our findings suggest that the Cel System supplement range may effectively reduce biological age and improve health metrics, warranting further investigation into its mechanistic pathways and long-term efficacy.

Keywords:  aging; epigenetic age change; epigenetic biomarker proxies; hallmarks of aging; nutraceutical longevity interventions; physiological age change

DOI:  https://doi.org/10.18632/aging.206221
Mol Med Rep. 2025 May;pii: 131. [Epub ahead of print]31(5):

Water extract of Humulus japonicus improves age‑related cognitive decline by inhibiting acetylcholinesterase activity and the acetylcholine signaling pathway.

Ju-Eun Kim, Kyeong-Seon Min, Jun Go, Hye-Yeon Park, Young-Keun Choi, In-Bok Lee, Jaewon Shin, Hyun-Ju Cho, Hong-Sik Kim, Dae Youn Hwang, Won-Keun Oh, Kyoung-Shim Kim, Chul-Ho Lee.

  The aging process is associated with a decline in certain cognitive abilities, including learning and memory. This age‑related cognitive decline is associated with a reduction in neurogenesis and alterations in the cholinergic system. Humulus japonicus (HJ), an ornamental plant in the family Cannabaceae, has been reported to exert beneficial effects against neurodegenerative pathophysiologies in mouse models of disorders such as Alzheimer's and Parkinson's disease. Despite the increasingly aging populations of numerous societies, no study has yet investigated the effects of HJ on cognitive decline associated with normal aging. The present study therefore aimed to examine the protective potential of HJ water (HJW) extract against age‑related cognitive decline and scopolamine‑induced cognitive impairment. The analyses revealed that the oral administration of HJW markedly improved novel objective recognition and spatial learning in the novel object recognition and Morris water maze tests, respectively, in aged mice. The administration of 600 mg/kg HJW further increased neurogenesis and CA1 thickness in the hippocampi of aged mice. In scopolamine‑induced cognitive impairment, administration of 400 or 600 mg/kg HJW markedly increased novel object recognition performance in scopolamine‑treated mice. The inhibitory effect of HJW on acetylcholinesterase (AChE) and the activation effects of HJW on the calcium/calmodulin‑dependent kinase (CaMK)IIα‑cAMP response element‑binding protein (CREB) and AKT‑glycogen synthase kinase‑3 β (GSK3β) pathways were further demonstrated. Overall, these results indicate that HJW administration improves cognitive function through the regulation of AChE activity and CaMKIIα‑CREB and AKT‑GSK3β pathways.

Keywords:  Humulus japonicus; acetylcholine; aging; cognitive function; scopolamine‑induced model

DOI:  https://doi.org/10.3892/mmr.2025.13496
Small. 2025 Mar 20. e2412611

Nanoparticle-Driven Skeletal Muscle Repair and Regeneration Through Macrophage-Muscle Stem Cell Interaction.

Lining Xu, Yingyu Zhang, Dingding Wang, Quanzhong Ren, Yi Wang, Zetong Zang, Anyi Guo, Jianxun Guo, Ling Wang, Renxian Wang, Yajun Liu.

  Macrophages are key innate immune cells in the muscle environment of sarcopenia patients, significantly influencing muscle stem cell (MuSC) proliferation and differentiation. However, prolonged activation of macrophages can hinder muscle recovery. In this study, it synthesizes lipoic acid-modified gold nanoparticles (LA-Au NPs) of varying sizes to evaluate their biocompatibility and immunomodulatory effects. The findings demonstrate that LA-Au NPs exhibit excellent biocompatibility with macrophages and promoted M2 polarization in a size-dependent manner. Mechanistically, LA-Au NPs facilitated metabolic reprogramming in macrophages by enhancing lysosomal autophagy and mitochondrial oxidative phosphorylation. Furthermore, macrophages are shown to chemotax toward MuSCs, regulating their proliferation via the chemokine system, inhibiting MuSC apoptosis, and enhancing differentiation under inflammatory conditions. In vivo studies have confirmed the safety and efficacy of LA-Au NPs in sarcopenia mice. To further enhance the effectiveness of LA-Au NPs, it investigates a delivery strategy that involves preconditioning macrophages with LA-Au NPs (Mac@Au NPs). Compared to the direct injection of LA-Au NPs, Mac@Au NPs demonstrate significantly greater benefits for muscle repair. This highlights the potential of macrophage therapy as a promising strategy for effective muscle regeneration and therapeutic intervention in sarcopenia.

Keywords:  gold nanoparticles; immunometabolism; macrophages; muscle stem cells; skeletal muscle regeneration

DOI:  https://doi.org/10.1002/smll.202412611
Eur J Intern Med. 2025 Mar 18. pii: S0953-6205(25)00090-1. [Epub ahead of print]

How to promote healthy aging across the life cycle.

Camilla Cocchi, Maria Beatrice Zazzara, Elena Levati, Riccardo Calvani, Graziano Onder.

  The global rise in aging populations is challenging healthcare systems, especially in developed countries. Despite advancements in healthcare and living standards, the extension of lifespan has not been matched by an equivalent improvement in healthspan, leading to a higher prevalence of chronic diseases and disabilities in older adults. This review examines strategies to promote healthy aging throughout the life cycle, emphasizing the importance of a comprehensive strategy that integrates individual, healthcare, and environmental approaches. Individual strategies include lifestyle factors like diet, physical activity, and social connections. Healthcare approaches focus on improving health literacy, vaccinations, and screenings. Environmental approaches aim to mitigate climate change, reduce pollution, and design longevity-ready cities. A comprehensive strategy combining individual approaches, public health measures, innovative policies, and community support is essential for helping populations live longer, healthier, and more independent lives. Looking forward, this will be complemented by personalized approaches, focusing on individual traits and biological backgrounds. The key to this lies in geroscience, which studies the biological and molecular mechanisms of aging and how they contribute to age-related diseases and functional decline, aiming to design targeted interventions to slow aging and improve quality of life. Artificial intelligence will play a key role in analyzing these complex factors and creating innovative solutions. In conclusion, aging is shaped by various factors, requiring more than one solution. A combination of comprehensive and personalized strategies can bridge the gap between public health measures and personalized care, offering the scientific insights needed to slow aging and enhance quality of life.

Keywords:  Geroscience; Healthy aging; Lifestyle interventions; Longevity; Personalized medicine

DOI:  https://doi.org/10.1016/j.ejim.2025.03.003
Nat Metab. 2025 Mar 14.

The cyclic metabolic switching theory of intermittent fasting.

Mark P Mattson.

Intermittent fasting (IF) and ketogenic diets (KDs) have recently attracted much attention in the scientific literature and in popular culture and follow a longer history of exercise and caloric restriction (CR) research. Whereas IF involves cyclic metabolic switching (CMS) between ketogenic and non-ketogenic states, KDs and CR may not. In this Perspective, I postulate that the beneficial effects of IF result from alternating between activation of adaptive cellular stress response pathways during the fasting period, followed by cell growth and plasticity pathways during the feeding period. Thereby, I establish the cyclic metabolic switching (CMS) theory of IF. The health benefits of IF may go beyond those seen with continuous CR or KDs without CMS owing to the unique interplay between the signalling functions of the ketone β-hydroxybutyrate, mitochondrial adaptations, reciprocal activation of autophagy and mTOR pathways, endocrine and paracrine signalling, gut microbiota, and circadian biology. The CMS theory may have important implications for future basic research, clinical trials, development of pharmacological interventions, and healthy lifestyle practices.

DOI: https://doi.org/10.1038/s42255-025-01254-5
Glob Med Genet. 2025 Jun;12(2): 100034

Noncoding RNAs evolutionarily extend animal lifespan.

Anyou Wang.

  The mechanisms underlying the evolution of lifespan across organisms remain mysterious. This study computes multiple large datasets and reveals that noncoding RNAs (ncRNAs), rather than proteins, drive animal lifespan evolution. Species in the animal kingdom evolutionarily increase their ncRNA length in their genomes, coinciding with trimming of the mitochondrial genome length. This leads to a low energy consumption and longevity. Notably, as species evolve and extend their lifespans, they tend to acquire long-lived ncRNA motifs while simultaneously losing short-lived ones, in contrast to the conservative patterns observed in protein evolution. These longevity-associated ncRNA motifs, such as GGTGCG, are particularly active in crucial tissues including the endometrium, ovaries, testes, and cerebral cortex. The ovary and endometrium carry more activating ncRNAs than the testis, offering insight into why women generally outlive men. Taken together, ncRNAs drive the evolution of the two most important traits of organisms: longevity and reproduction, and they execute many more fundamental functions than those conventionally thought. This discovery provides the foundation for combating longevity and aging.

Keywords:  Aging; Evolution; Extend; Lifespan; Longevity; NcRNA; Noncoding RNAs

DOI:  https://doi.org/10.1016/j.gmg.2024.100034
3 Biotech. 2025 Apr;15(4): 88

Astaxanthin: a nature's versatile compound utilized for diverse applications and its therapeutic effects.

Anjali Bharti, Vinita Hooda, Utkarsh Jain, Nidhi Chauhan.

  Astaxanthin (ASTX), red-colored xanthophyll, also known as the "king of carotenoids" exhibits a strong antioxidant property that can be naturally found in green algae Haematococcus pluvialis, red yeast Phaffia rhodozyma, and various aquatic species including salmon, krill, trout, and fish eggs. Due to their strong antioxidant qualities, ASTX nanoparticles may be crucial in fighting against phytotoxicity caused by heavy metal ions. Similarly, it may also reduce the uptake of heavy metal, i.e. cadmium, and translocation by improving the morpho-physiological profiles of plants. Furthermore, it can also have the ability to scavenge free radicals, therefore, it can protect plants from reactive oxygen species (ROS). Implementing ASTX nanoparticles on crops can also help to achieve higher food production while minimizing toxic effects. Additionally, it can also possess several therapeutic activities including anti-cancerous, anti-diabetic, antioxidant, anti-aging, anti-inflammation, hepatoprotective, and cardiovascular, etc. that can be beneficial to treat various types of diseases in humans and animals. Recently, it has gained more interest in food, agriculture, aquaculture, neutraceuticals, and pharmaceutical industries due to its wide range of applications including food-coloring agents, food supplements, and strong antioxidant property that helps in skin protection, and boosts immune function. However, ASTX possesses poor water solubility and chemical stability so the implementation of ASTX on human health is facing various issues. Therefore, nanoencapsulation of ASTX is very crucial to improve its chemical stability and solubility, ultimately leading to its bioavailability and bioaccessibility. Recently, ASTX has been commercially available with specific dosages in the market mainly in the form of tablets, gels, powders, creams, syrups, etc. The current review mainly highlights the present state of ASTX nanoparticle applications in various fields explaining its natural and synthetic sources, extraction methods, chemical structure, stability, nanoformulations, nano encapsulation, and various commercial aspects.

Keywords:  Antioxidant activity; Nanoastaxanthin; Nanoformulations; Nano encapsulation; Therapeutic applications

DOI:  https://doi.org/10.1007/s13205-025-04241-5
Trials. 2025 Mar 18. 26(1): 94

Circuit training intervention for cognitive function, gut microbiota, and aging control: study protocol for a longitudinal, open-label randomized controlled trial.

Keishi Soga, Michio Takahashi, Akari Uno, Takamitsu Sinada, Kentaro Oba, Keisei Kawashima, Yasuko Tatewaki, Taizen Nakase, Yasuyuki Taki.

BACKGROUND: Long-term exercise is increasingly considered an effective strategy to counteract cognitive decline associated with aging. Previous studies have indicated that circuit training exercises integrating aerobic and resistance modalities positively affect cognitive function. Furthermore, a growing body of evidence suggests that long-term exercise alters the gut microbiota, leading to an optimal environment for cognitive enhancement. Recent empirical evidence suggests that exercise plays a significant role in modulating aging-control factors at the protein level. Although the interaction between exercise and cognitive function is multifaceted, most studies have only examined a direct pathway from exercise to cognitive function. Therefore, this study aims to elucidate the effects of long-term circuit training on cognitive function through a comprehensive analysis of factors such as gut microbiota and proteins related to aging control.
METHODS: A total of fifty-one participants will be randomly assigned to either the circuit training or waitlist control group. The intervention group will participate in a circuit training program developed by Curves Japan Co., Ltd. two to three times weekly for 16 weeks. The control group will continue their usual daily routines without participating in any new active lifestyle program. The participants will undergo cognitive assessments at baseline and after the intervention. Fecal and blood samples for protein analysis will be collected before and after the intervention. The effect of exercise on cognition will be analyzed by comparing the measured outcomes before and after the intervention. The associations among these outcomes will be assessed using a linear mixed model and structural equation modeling approaches.
DISCUSSION: This study aims to provide the first insights into the comprehensive effects of exercise on cognitive function from the perspectives of gut microbiota and aging control. The findings are expected to contribute to improving brain health and combating age-related cognitive decline. Furthermore, the findings may help establish new guidelines for future studies on the relationship between exercise and cognitive function.

DOI: https://doi.org/10.1186/s13063-025-08807-9
Redox Biol. 2025 Mar 14. pii: S2213-2317(25)00111-9. [Epub ahead of print]82 103598

Transgenerational inheritance of mitochondrial hormetic oxidative stress mediated by histone H3K4me3 and H3K27me3 modifications.

Yimin Li, Chongyang Wang, Xiaoxia Fu, Dan Wu, Chenyang He, Wenyu Dai, Xiaoyang Yue, Zhenhuan Luo, Jing Yang, Qin-Li Wan.

  Mitochondrial hormetic oxidative stress (mtHOS) is crucial in physiology and disease; however, its effects on epigenetic inheritance and organism fitness across generations remains elusive. Utilizing the C. elegans as a model, we elucidate that parental exposure to mtHOS not only elicits a lifespan extension in the exposed individuals but also confers this longevity advantage to the progeny through the transgenerational epigenetic inheritance (TEI) mechanism. This transgenerational transmission of lifespan prolongation depends on the activation of the UPRmt and the synergistic action of the transcription factors DAF-16/FOXO and SKN-1/Nrf2. Additionally, the H3K4me3 and H3K27me3 serve as epigenetic mediators, selectively marking and regulating the expression of genes associated with oxidative stress response and longevity determination. Our findings illuminate the mechanisms underlying the implementation and transmission of mtHOS, revealing a sophisticated interplay among oxidative stress response genes and chromatin remodeling that collectively enhances the progeny's adaptive resilience to future challenges.

Keywords:  Caenorhabditis elegans; Histone modification; Longevity; Mitochondrial hormetic oxidative stress; Transgenerational epigenetic inheritance; UPR(mt)

DOI:  https://doi.org/10.1016/j.redox.2025.103598
J Craniofac Surg. 2025 Mar 17.

Hybrid Fillers Personal Experience of Premixing Calcium Hydroxylapatite and Hyaluronic Acid for Natural Face Reshaping.

Massimo Vitale, Elena Zappia, Hassan Galadari, Fernando Felice, Andrea Lazzarotto, Natalia Sukmanskaya, Kyu-Ho Yi.

OBJECTIVE: This retrospective study evaluates the efficacy and safety of premixed calcium hydroxylapatite (CaHA) and hyaluronic acid (HA) hybrid fillers for facial reshaping and rejuvenation, focusing on natural outcomes with long-term follow-up over 12 months.
METHODS: Forty-six patients (ages 45-65) underwent hybrid filler treatments using a 1:1 premixed formulation of CaHA and HA. Injection techniques targeted specific facial zones using cannulas for subdermal delivery. Standardized 3D imaging and the Merz Aesthetics Scale (CR-MASJ) were used to assess lifting effects and volume restoration. The Global Aesthetic Improvement Scale (GAIS) measured patient satisfaction.
RESULTS: Improvements in skin laxity, volume restoration, and facial contouring were noted as early as 3 months post-treatment and sustained through 12 months. Premixed hybrid fillers demonstrated enhanced biostimulatory effects compared with standalone CaHA or HA, promoting neocollagenesis and providing immediate and lasting results. Adverse events were minimal, with no significant complications reported.
CONCLUSION: Premixing CaHA and HA offers a safe, effective, and reproducible technique for natural facial reshaping and rejuvenation. The combination enhances skin quality while providing immediate volumization and long-term collagen stimulation, meeting the aesthetic expectations of patients seeking minimally invasive anti-aging solutions.

DOI: https://doi.org/10.1097/SCS.0000000000011232
Front Nutr. 2025 ;12 1548072

Adherence to the cMIND and AIDD diets and their associations with anxiety in older adults in China.

Yana Qi, Xinyu Xue, Ningsu Chen, Jie Gong, Dongyu Mu, Kai Zhao, Mengnan Zhao, Youping Li, Lei Shi, Jiajie Yu.

   Introduction: Anxiety is highly prevalent among older adults, and dietary interventions targeting nutrition may offer effective, practical strategies for preventing mental disorders. This study aimed to explore the association between the cMIND diet, anti-inflammatory dietary diversity (AIDD), and the risk of anxiety in older adults.
Methods: A cross-sectional analysis was conducted using data from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS). Anxiety symptoms were assessed using the Generalized Anxiety Disorder (GAD-7) scale, while adherence to the cMIND diet and AIDD was evaluated through a food frequency questionnaire. Univariable and multivariable logistic regression analyses were performed to examine associations between dietary patterns and anxiety risk, with odds ratios (ORs) and 95% confidence intervals (CIs) reported. Random forest analysis was used to identify key factors influencing anxiety, and sensitivity analyses were conducted to test the robustness of the results.
Results: A total of 13,815 participants aged 65 and older were included, with 1,550 (11.2%) identified with anxiety. Multivariable logistic models indicated that adherence to the cMIND diet or higher AIDD was associated with a 16-26% reduced risk of anxiety, with the adjusted ORs (95% CIs) for the cMIND diet ranging from 0.75 (0.64-0.87) to 0.75 (0.61-0.91), and for AIDD from 0.74 (0.62-0.88) to 0.84 (0.73-0.96). Sensitivity analyses confirmed the stability of these findings. Depression and sleep quality were identified as the most important factors contributing to anxiety, while diet was one of the few modifiable factors.
Conclusion: This study provides evidence supporting the association between diet and anxiety in older adults, highlighting the potential of promoting healthy dietary patterns and targeted nutritional interventions as effective strategies for improving mental health in the aging population.

Keywords:  China; anti-inflammatory dietary diversity; anxiety; cMIND diet; older

DOI:  https://doi.org/10.3389/fnut.2025.1548072
J Gerontol A Biol Sci Med Sci. 2025 Mar 07. pii: glaf013. [Epub ahead of print]80(4):

Correction to: Yo-Yo Dieting Delays Male Drosophila melanogaster Aging Through Enhanced Mitochondrial Function, Relative to Sustained High-Calorie Diet Feeding.

DOI: https://doi.org/10.1093/gerona/glaf013
J Appl Physiol (1985). 2025 Mar 18.

PoWeR elicits intracellular signaling, mitochondrial adaptations, and hypertrophy in multiple muscles consistent with endurance and resistance exercise training.

Christian J Elliehausen, Szczepan S Olszewski, Dennis M Minton, Audrey L Spiegelhoff, Carolyn G Shult, Wenyuan G Zhu, Troy A Hornberger, Adam R Konopka.

  Physical activity guidelines recommend both endurance and resistance exercise to improve and maintain overall health. Recently, progressive weighted wheel running (PoWeR), a voluntary, progressive, and high-volume exercise paradigm, was posited as a singular prototype of combined endurance and resistance exercise in mice as evident by enhanced capillarization and hypertrophy of select plantar flexor muscles. Despite growing interest in this model, it remains incompletely characterized if PoWeR resembles the acute and chronic responses to resistance and/or endurance exercise in humans. Therefore, the purpose of this study was to assess canonical signaling events, mitochondrial bioenergetics, and cellular adaptations across multiple extensor and flexor muscles of the fore- and hindlimbs that may be conducive for whole-body functional improvements as traditionally observed in humans. 8-weeks of PoWeR (~8km/day) improved glucose metabolism, exercise capacity, body composition, and bone mineral density as well as increased mass, myofiber CSA, and oxidative myofiber type distribution in the soleus, plantaris, and FDL. Using two ex-vivo high-resolution flourorespirometry protocols that model in vivo physiological conditions, PoWeR decreased mitochondrial ADP sensitivity which was accompanied by greater mitochondrial H2O2 emissions, respiration, conductance, and protein content in the vastus lateralis, gastrocnemius, and triceps in muscle-specific fashion. Three days of short-term PoWeR stimulated mTORC1 and AMPK signaling in soleus, plantaris and/or FDL in line with the hypertrophic and metabolic adaptations observed with long-term training. Collectively, these data support PoWeR as a suitable paradigm in mice to model the acute signaling and chronic adaptations associated with endurance and resistance exercise in humans.

Keywords:  Hypertrophy; mTOR; metabolism; mitochondria; reactive oxygen species

DOI:  https://doi.org/10.1152/japplphysiol.00872.2024
J Pharm Biomed Anal. 2025 Mar 12. pii: S0731-7085(25)00159-1. [Epub ahead of print]260 116818

Elucidating the mechanisms of Shenwu Capsule in improving the cognitive decline in aging based on the UPLC-Q-TOF-MS, network pharmacology, and experimental validation.

Zizhao Cheng, Shengyao Wang, Xuesi Hua, Li Zhang, Boya Li, Huiling Li, Yunya Bai, Yali Li, Jinping Hao, Jianxiong Wang, Lingyi Zhao, Dan Gao, Lan Zhang.

  Given the growing incidence of dementia-related disorders in the aging population, identifying effective treatments for age-related cognitive decline (ARCD) is crucial. Shenwu Capsule (SWC), shown to have therapeutic efficacy in phase III clinical trials for senile dementia, has unclear mechanisms and active ingredients. Aged mice were administered SWC orally for three months, and behavioral tests, including the Morris water maze, Y maze, and novel object recognition, assessed learning and memory. Neuronal damage was evaluated using histopathology, and the levels of Aβ and phosphorylated tau proteins were measured. UPLC-Q-TOF-MS identified 11 components of SWC capable of crossing the blood-brain barrier (BBB), and network pharmacology was employed to explore their potential mechanisms. Through various detection methods, including transmission electron microscopy, Western blotting, qRT-PCR, ELISA, and immunofluorescence, six key targets (AKT1, TNF, TP53, SRC, EGFR, BCL2) were elucidated. GO and KEGG pathway analyses revealed that the PI3K/Akt signaling pathway plays a crucial role in the pharmacological effects of SWC. SWC was found to suppress neuronal apoptosis by activating the PI3K/Akt/Bcl-2 signaling pathway, as demonstrated by changes in mRNA and protein levels. Histological analysis further showed that SWC treatment restored mitochondrial morphology in the hippocampus of aged mice. Molecular docking simulations confirmed strong binding affinities between the active components and key targets. Psoralidin, a component with strong molecular docking potential, was shown in vitro to activate the PI3K/Akt/Bcl-2 pathway, reduce ROS, decrease apoptosis, improve mitochondrial morphology, and stabilize mitochondrial membrane potential. These protective effects were blocked by the PI3K inhibitor LY294002. Overall, SWC ameliorates ARCD through modulation of the PI3K/Akt/Bcl-2 signaling pathway, with psoralidin identified as a potential active ingredient.

Keywords:  Age-related cognitive decline; Network pharmacology; PI3K/Akt/Bcl-2 signaling pathway; Psoralidin; Shenwu capsule; UPLC-Q-TOF-MS

DOI:  https://doi.org/10.1016/j.jpba.2025.116818