bims-caglex 2025-05-11 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2025–05–11
24 papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

Synbiotic pineapple beverage increases life span in Caenorhabditis elegans, ameliorates cognitive impairment, and restores gut microbiome diversity in D-galactose-induced aged C57BL/6 mice.
From telomeres and senescence to integrated longevity medicine: redefining the path to extended healthspan.
PDRN prevents SIRT1 degradation by attenuating autophagy during skin aging.
Berberine Extends Lifespan in C. elegans Through Multi-Target Synergistic Antioxidant Effects.
Maral Root Extract and Its Main Constituent 20-Hydroxyecdysone Enhance Stress Resilience in Caenorhabditis elegans.
Discovery of Non-antibacterial Enrofloxacin Derivatives with Emerging Antiaging Effects through Drug Repurposing and Secondary Development.
Unlocking the Potential of Curcumae Rhizoma Aqueous Extract in Stress Resistance and Extending Lifespan in Caenorhabditis elegans.
Replacement as an aging intervention.
Epimedii Folium and Curculiginis Rhizoma ameliorate age-related cognitive decline and neuroinflammation through modulation of the NLRP3 inflammasome.
Calorie-restriction treatment mitigates the aging in rat liver model.
Dietary and pharmacological energy restriction and exercise for healthspan extension.
Oleoylethanolamine precursor triggers lipolysis during Time-Restricted Intermittent Fasting and promotes longevity and healthy aging of Caenorhabditis elegans.
Terpenes: natural compounds found in plants as potential senotherapeutics targeting senescent mesenchymal stromal cells and promoting apoptosis.
Short- and Long-Term Effects of Adding Topical Cosmetics to a Dermatological Procedure (Thermage): A Randomized Controlled Comparative Study Exploring the Synergistic Effects.
Adherence to EAT-Lancet diet, biological aging and life expectancy in the UK Biobank: a cohort study.
Clinical Case Study Investigating a Longevity Daily Serum for Japanese Women With Facial Skin Aging.
Lactiplantibacillus brownii strain MH-1 prolongs healthspan and improves stress resistance in Caenorhabditis elegans.
Methylation clocks for evaluation of anti-aging interventions.
Multi-omics analysis reveals the attenuation effect of C-phycocyanin on aging-induced subfertility in female mice.
Clinical Evaluation of an Innovative CaHA Bio-Stimulator in Facial Rejuvenation: 1 Year Follow-Up.
Senolytic treatment to rescue hallmarks of senescence in lymph node fibroblasts from patients with rheumatoid arthritis: Implications for premature aging and potential therapeutic intervention in early rheumatoid arthritis.
Longevity concept by regenerative medicine methods synergy: exosome therapy, functional medicine, and advanced multi-wavelengths laser therapy.
Role of Stem Cells in Ageing and Age-related Diseases.
The Effects of Plasma Exosomes of Young Individuals Compared to Old Ones on Age-Related Inflammation and Lineage Differentiation of CD34+ Umbilical Cord Blood Hematopoietic Stem Cells.

Biogerontology. 2025 May 03. 26(3): 99

Synbiotic pineapple beverage increases life span in Caenorhabditis elegans, ameliorates cognitive impairment, and restores gut microbiome diversity in D-galactose-induced aged C57BL/6 mice.

Neelam Anil Revankar, Siddaraju Anusha, Serva Peddha Muthukumar, Pradeep Singh Negi.

  The incidence of age-associated ailments has increased proportionately with the expansion of the aging demographic. This study aimed to evaluate the anti-aging potential of synbiotic pineapple beverage formulated with 100% pineapple juice, 1% inulin, and Lacticaseibacillus rhamnosus ATCC 53103 (10 log CFU) in Caenorhabditis elegans and D-galactose age-induced mice. The synbiotic juice-treated nematodes exhibited a 24.52% increase in their lifespan, accompanied by lower levels of reactive oxygen species and improved structural functions. In vivo studies demonstrated that synbiotic treatment positively influences age-induced mice's cerebellar function and spatial memory. Additionally, the synbiotic beverage containing 8-10 log CFU of Lacticaseibacillus rhamnosus showed a protective effect against hippocampal neuron damage. The control group displayed a higher Firmicutes/Bacteroides (F/B) ratio, whereas the significantly lower F/B ratio in the diseased groups indicated a reversal of microbial imbalance caused by D-galactose exposure. Furthermore, the consumption of synbiotic beverage mitigated telomere shortening in aged mice. The results highlight the anti-aging effects of a pineapple beverage formulated with Lacticaseibacillus rhamnosus and inulin as a synbiotic intervention. This study suggests that dietary interventions incorporating prebiotics and probiotics may serve as promising strategy for combating age-related disorders and promoting healthy aging.

Keywords:   Caenorhabditis elegans ; Lacticaseibacillus rhamnosus ; D-galactose-induced aged mice; Inulin; Pineapple; Synbiotics

DOI:  https://doi.org/10.1007/s10522-025-10239-6
Biogerontology. 2025 May 05. 26(3): 107

From telomeres and senescence to integrated longevity medicine: redefining the path to extended healthspan.

Virginia Boccardi.

  Despite significant advances in aging research, translating these findings into clinical practice remains a challenge. Aging is a complex, multifactorial process shaped by many factors including genetic, metabolic, and environmental factors. While medical advancements have extended lifespan, healthspan remains constrained by cellular senescence, telomere attrition, and systemic inflammation-core hallmarks of biological aging. However, emerging evidence suggests that telomere dynamic is not inevitable but can be influenced by oxidative stress, lifestyle choices, and metabolic regulation. This review examines how telomere-based biomarkers and metabolic interventions can drive personalized longevity medicine, enabling targeted strategies to delay aging. Furthermore, it highlights the integration of geroscience into clinical practice-integrated longevity medicine leveraging biomarker tracking, metabolic therapies, and preventive interventions-to redefine aging as a modifiable process, ultimately extending both lifespan and healthspan.

Keywords:  Aging; Geroscience; Healthspan; Integrate medicine; Longevity; Telomeres

DOI:  https://doi.org/10.1007/s10522-025-10246-7
PLoS One. 2025 ;20(5): e0321005

PDRN prevents SIRT1 degradation by attenuating autophagy during skin aging.

Jingjing Chen, Fanshan Qiu, Jianfeng Shi, Wei Huang, Chenyu Zhao, Qianqian Han.

Polydeoxyribonucleotide (PDRN) is a low molecular weight linear polyribonucleotide fragment derived from salmon sperm, known for its potential in tissue regeneration and anti-inflammatory applications. However, its specific function in cellular senescence is yet to be fully understood. Silent information regulator 1 (SIRT1), an NAD + -dependent deacetylase, plays a crucial role in regulating cellular aging and tumorigenesis. Notably, SIRT1 levels decrease with age in both mice and during cellular senescence, highlighting its significance in anti-aging processes. This study assessed the effects of PDRN on cellular aging induced by ultraviolet B (UVB) or hydrogen peroxide (H2O2) and investigated the mechanisms of its protective effects against aging at the cellular level. Our data demonstrated that PDRN treatment mitigated the decline in cell viability and inhibited cell aging when exposed to UVB or H2O2. Furthermore, PDRN ameliorated UVB-induced epidermal thickening in mouse skin. Mechanically, we found that PDRN treatment led to a reduction in nuclear autophagy and the formation of cytoplasmic stress granules by preventing the accumulation of damaged LC3 in the nuclear and inhibiting the degradation of SIRT1 and p62 in the cytoplasm during cellular senescence. In conclusion, PDRN exhibits antioxidant and anti-aging properties by diminishing autophagy and enhancing SIRT1 expression. These results suggest that PDRN has potential as a therapeutic compound for reducing skin aging induced by UVB or H2O2 through the modulation of SIRT1 levels.

DOI: https://doi.org/10.1371/journal.pone.0321005
Antioxidants (Basel). 2025 Apr 09. pii: 450. [Epub ahead of print]14(4):

Berberine Extends Lifespan in C. elegans Through Multi-Target Synergistic Antioxidant Effects.

Yingshuo Bei, Ting Wang, Shuwen Guan.

  Aging is a process of gradual functional decline in complex physiological systems and is closely related to the occurrence of various diseases. Berberine, a bioactive alkaloid derived from Coptis chinensis (Huanglian), has emerged as a promising candidate for anti-aging interventions. This study comprehensively investigated the lifespan-extending effects and molecular mechanisms of berberine in C. elegans through integrated approaches including lifespan assays, locomotor activity analysis, oxidative stress challenges, and transcriptomic profiling. Furthermore, genetic models of mutant and transgenic worms were employed to delineate their interactions with the insulin/IGF-1 signaling (IIS) pathway. Our results demonstrate that berberine extended the mean lifespan of wild-type worms by 27%. By activating transcription factors such as DAF-16/FOXO, HSF-1, and SKN-1/NRF2, berberine upregulated antioxidant enzyme expression, reduced lipofuscin accumulation, and improved stress resistance. Transcriptomic analysis revealed significant changes in lipid metabolism-related genes, particularly in pathways involving fatty acid synthesis, degradation, and sphingolipid metabolism. These findings establish that berberine exerts multi-target anti-aging effects through coordinated activation of stress-responsive pathways and metabolic optimization, providing mechanistic insights for developing natural product-based geroprotective strategies.

Keywords:  C. elegans; anti-aging; antioxidant; berberine; insulin/IGF-1 signaling pathways

DOI:  https://doi.org/10.3390/antiox14040450
Int J Mol Sci. 2025 Apr 15. pii: 3739. [Epub ahead of print]26(8):

Maral Root Extract and Its Main Constituent 20-Hydroxyecdysone Enhance Stress Resilience in Caenorhabditis elegans.

Velislava Todorova, Monika N Todorova, Martina S Savova, Kalin Ivanov, Milen I Georgiev, Stanislava Ivanova.

  As human life expectancy continues to rise, managing age-related diseases and preserving health in later years remain significant challenges. Consequently, there is a growing demand for strategies that enhance both the quality and the duration of life. Interventions that promote longevity, particularly those derived from natural sources, are popular for their potential to address age-related health concerns. Adaptogens-herbs, roots, and mushrooms-are valued in food science and nutrition for their ability to enhance resilience and overall well-being. Among these, Rhaponticum carthamoides (Willd.) Iljin, known as maral root (Russian leuzea), holds a prominent place in Siberian traditional medicine. The root extract, abundant in bioactive compounds such as flavonoids and phytoecdysteroids, is reputed for reducing fatigue, boosting strength, and offering immunomodulatory benefits. However, the effects of the plant extract on lifespan and age-related decline remains poorly studied. This study investigates the effect of maral root extract and phytoecdysteroids-ecdysterone, ponasterone, and turkesterone-on aging using Caenorhabditis elegans as a model organism. A sensitive liquid chromatography method with photodiode array detection was developed and validated to quantify the phytoecdysteroids in the extract. Behavioural and stress-response assays revealed that maral root not only extends lifespan but also significantly enhanced healthspan, stress resilience, and fitness in the nematodes. Additionally, treatment with ecdysterone, the most abundant compound in the root extract, improved healthspan by enhancing stress response. These findings underscore the potential of maral root as a natural adaptogen to mitigate age-related decline, providing valuable insights into natural longevity interventions.

Keywords:  20-hydroxyecdysone; Caenorhabditis elegans; Rhaponticum carthamoides; adaptogens; aging; lifespan; longevity

DOI:  https://doi.org/10.3390/ijms26083739
J Med Chem. 2025 May 09.

Discovery of Non-antibacterial Enrofloxacin Derivatives with Emerging Antiaging Effects through Drug Repurposing and Secondary Development.

Sicong Qiao, Xin Chen, Youyou Chen, Yihe Song, Donglei Shi, Zhifan Mao, Jian Li, Yunyuan Huang, Wenwen Liu.

Aging induces dysfunction and increases the risk of chronic diseases in the elderly, positioning the development of antiaging drugs to the forefront of research. Drug repurposing offers an efficient strategy for identifying antiaging lead compounds. In this study, we employed phenotypic screening and discovered that enrofloxacin could extend the lifespan in Caenorhabditis elegans. Based on these findings, we conducted rational drug design to eliminate its antibacterial activity while maintaining the lifespan-extending effect, with the goal of developing safe and novel antiaging compounds. Consequently, JX10 exhibited minimal antibacterial activity and competent antiaging effects in C. elegans, senescent cells, and aged mice. In terms of its mechanism, JX10 acted as a senomorphic agent by suppressing the expression of p38 MAPK and NF-κB. Furthermore, JX10 demonstrated favorable safety and pharmacokinetic properties, supporting the feasibility of JX10 as a promising candidate with the potential for therapeutic interventions in aging and aging-related diseases.

DOI: https://doi.org/10.1021/acs.jmedchem.5c00021
Molecules. 2025 Apr 08. pii: 1668. [Epub ahead of print]30(8):

Unlocking the Potential of Curcumae Rhizoma Aqueous Extract in Stress Resistance and Extending Lifespan in Caenorhabditis elegans.

Linyao Jing, Yanlin Zhao, Lijun Jiang, Fei Song, Lu An, Edmund Qi, Xueqi Fu, Jing Chen, Junfeng Ma.

  The enhancement of stress resistance is crucial for delaying aging and extending a healthy lifespan. Traditional Chinese medicine (TCM), a cherished treasure of Chinese heritage, has shown potential in mitigating stress and promoting longevity. This study integrates network pharmacology and in vivo analysis to investigate the mechanisms and effects of Curcumae Rhizoma (C. Rhizoma), known as "E Zhu" in Chinese. Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) identified 10 active compounds in its aqueous extract, interacting with 128 stress-related targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed pathways such as stress response, FoxO signaling, and insulin resistance. In Caenorhabditis elegans, 10 mg/mL of C. Rhizoma aqueous extract improved resistance to UV, thermal, oxidative, and pathogen-induced stress, extending lifespan in a dose-dependent manner. Mechanistically, it reduced reactive oxygen species (ROS), increased superoxide dismutase (SOD) activity, and enhanced UV resistance via the insulin/IGF-1 pathway and DAF-16 translocation. Molecular docking highlighted hexahydrocurcumin (HHC) and related compounds as key bioactives. Furthermore, we also observed that C. Rhizoma aqueous extract significantly extended both the lifespan and healthspan of nematodes. These findings highlight the potential of C. Rhizoma in stress mitigation and longevity promotion, offering valuable insights into the therapeutic applications of TCM.

Keywords:  Caenorhabditis elegans; IIS; ROS; molecular docking; network pharmacology; stress resistance

DOI:  https://doi.org/10.3390/molecules30081668
Nat Aging. 2025 May 08.

Replacement as an aging intervention.

Sierra Lore, Jesse R Poganik, Anthony Atala, George Church, Vadim N Gladyshev, Morten Scheibye-Knudsen, Eric Verdin.

Substantial progress in aging research continues to deepen our understanding of the fundamental mechanisms of aging, yet there is a lack of interventions conclusively shown to attenuate the processes of aging in humans. By contrast, replacement interventions such as joint replacements, pacemaker devices and transplant therapies have a long history of restoring function in injury or disease contexts. Here, we consider biological and synthetic replacement-based strategies as aging interventions. We discuss innovations in tissue engineering, such as the use of scaffolds or bioprinting to generate functional tissues, methods for enhancing donor-recipient compatibility through genetic engineering and recent progress in both cell therapies and xenotransplantation strategies. We explore synthetic approaches including prostheses, external devices and brain-machine interfaces. Additionally, we evaluate the evidence from heterochronic parabiosis experiments in mice and donor-recipient age-mismatched transplants to consider whether systemic benefits could result from personalized replacement approaches. Finally, we outline key challenges and future directions required to advance replacement therapies as viable, scalable and ethical interventions for aging.

DOI: https://doi.org/10.1038/s43587-025-00858-6
J Ethnopharmacol. 2025 May 02. pii: S0378-8741(25)00567-7. [Epub ahead of print]348 119883

Epimedii Folium and Curculiginis Rhizoma ameliorate age-related cognitive decline and neuroinflammation through modulation of the NLRP3 inflammasome.

Jiaqi Ji, Biqun Zhang, Junzuo Zheng, Xuesong Zhang, Xiaosong Hu, He Zhu, Ping Wang, Zhou Lan.

   ETHNOPHARMACOLOGICAL RELEVANCE: Age-related cognitive decline and neuroinflammation are significant contributors to neurodegenerative diseases. In Traditional Chinese Medicine, aging is often associated with "kidney deficiency," a concept linked to impaired bone marrow production and brain function. Epimedii Folium and Curculiginis Rhizoma (XY), a classic herbal pair used to tonify the kidney, are traditionally employed to enhance vitality, bone health, and cognitive function. While previous studies suggest XY's efficacy in pathological models, its impact on natural aging process requires further investigation.
AIM OF THE STUDY: This study aimed to investigate the neuroprotective effects of XY against cognitive impairment and neuroinflammation in naturally aged mice and to explore the underlying mechanisms.
MATERIALS AND METHODS: Network pharmacology was used to identify potential targets and pathways, while molecular docking assessed the binding interactions between active compounds from XY and key target proteins. Naturally aged mice were orally treated with XY (2.34, 4.68 g/kg/day) for 26 days. Cognitive function was assessed using behavioral tests. Histological analysis, ELISA, real-time PCR, and Western blotting were employed to evaluate hippocampal neuronal damage, inflammatory markers, senescence-related proteins, and NLRP3 inflammasome components.
RESULTS: Network pharmacology identified key targets and pathways associated with aging and neuroinflammation. Molecular docking confirmed strong binding affinities between active components (e.g., Icariin, Epimedin B, Epimedin C) and relevant protein targets. In vivo, XY treatment significantly improved cognitive performance, ameliorated hippocampal neuronal damage, and suppressed microglial activation in aged mice. Furthermore, XY downregulated the expression of senescence markers (p53, p21, p16, CDK6), pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IFN-γ), factors associated with the senescence-associated secretory phenotype (SASP), and key components indicative of NLRP3 inflammasome activation (ASC, Caspase-1, IL-1β).
CONCLUSIONS: XY alleviates age-related cognitive decline and neuroinflammation in naturally aged mice. These beneficial effects are mediated, at least in part, by reducing inflammatory mediators, modulating microglial activation, attenuating cellular senescence pathways, and suppressing NLRP3 inflammasome activity. These findings highlight the therapeutic potential of XY for managing age-related cognitive impairment and associated neuroinflammation.

Keywords:  Aging; Cognitive decline; Curculiginis Rhizoma; Epimedii Folium; Network pharmacology; Neuroinflammation

DOI:  https://doi.org/10.1016/j.jep.2025.119883
Biogerontology. 2025 May 07. 26(3): 108

Calorie-restriction treatment mitigates the aging in rat liver model.

L Urlandini, A E Leonetti, F Conforti, A Perri, D Lofaro, G Antonucci, M Mandalà, S Bossio, S Di Agostino, V Rago.

  The aging process promotes progressive impairment of homeostasis and the increase of the risk of disease and death. A major hallmark of the aging process is the systemic chronic inflammation which strongly contributes to the onset of aging-related diseases. In the liver, the aging condition drives the hepatocytes to develop a metabolic dysfunction-associated steatosis. Caloric restriction (CR) is a remarkable strategy to delay biological aging, occurring through several mechanisms. In this study we aimed to explore, employing an in vivo rat model, the impact of CR on aging-mediated liver inflammation markers. The experiments were performed on 14 male Sprague-Dawley rats (24 months old). At 18 months old, rats were allocated into two groups: the normal diet (ND) group was continued ad libitum diet, and the CR regimen group was fed a diet of the same chow restricted to 60% of the intake. All animals were sacrificed at 24 months old. Compared to the ND group, morphological examination of the liver revealed a lower level of fibrosis in the CR group, concomitantly with a reduced expression of key fibrotic markers, such as collagen I, fibronectin, and αSMA. Furthermore, CR improved the liver oxidative balance, as showed by the increased expression of two scavenging enzymes, SOD1/SOD. Moreover, we reported concomitant reduction of NLRP3 inflammasome signalling. Interestingly, CR significantly improved the signalling of key members of the nutrition-sensitizing affected by aging, AMPK/SIRT1/LKB1. Collectively our findings support the evidence on the metabolic benefits of CR about aging-related liver inflammation, by inducing a morphological improvement that mirrors the decrease in the expression of inflammatory molecular markers.

Keywords:  Aging; Caloric restriction; Fibrosis; Inflammation; Liver

DOI:  https://doi.org/10.1007/s10522-025-10245-8
Trends Endocrinol Metab. 2025 May 02. pii: S1043-2760(25)00076-1. [Epub ahead of print]

Dietary and pharmacological energy restriction and exercise for healthspan extension.

Maria Lastra Cagigas, Isabella De Ciutiis, Andrius Masedunskas, Luigi Fontana.

  Extending healthspan - the years lived in optimal health - holds transformative potential to reduce chronic diseases and healthcare costs. Dietary restriction (DR), particularly when combined with nutrient-rich diets and exercise, is among the most effective, evidence-based strategies for enhancing metabolic health and longevity. By targeting fundamental pathways, it mitigates the onset and progression of obesity, type 2 diabetes (T2D), cardiovascular disease (CVD), neurodegeneration, and cancer. This review synthesizes human data on the impact of DR and exercise on metabolic and age-related diseases, while emphasizing key biological mechanisms such as nutrient sensing, insulin sensitivity, inflammation, mitochondrial function, and gut microbiota. We also examine the emerging role of pharmacologically induced DR, focusing on glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) that partially mimic DR and present opportunities for chronic disease prevention.

Keywords:  GLP-1 receptor agonists; clinical trials; dietary restriction; endurance and resistance training; healthspan; metabolic health; preventive healthcare

DOI:  https://doi.org/10.1016/j.tem.2025.04.001
J Physiol Biochem. 2025 May 07.

Oleoylethanolamine precursor triggers lipolysis during Time-Restricted Intermittent Fasting and promotes longevity and healthy aging of Caenorhabditis elegans.

Thondimuthu Vinitha, Rajasekharan Sharika, Krishnaswamy Balamurugan.

  Intermittent fasting (IF), Time-Restricted Intermittent Fasting (TRIF), and fasting-mimicking diets have gained popularity among weight loss programs. The body efficiently utilizes its energy reserves to activate metabolic processes in response to food intake. Modifying food regimens can alter/extend life span and promote healthy aging by activating specific metabolic processes. However, changes in general lipid metabolism, especially the alteration in N-acylethanolamide (NAE) regulation and their role in promoting lipolysis and extending life span during TRIF, are still inadequately explored. To bridge the knowledge gap, this study focuses on enhancing Oleoylethanolamine (OEA), a precursor molecule that instigates satiety, promotes lipolysis and extends the life span of model system, Caenorhabditis elegans. TRIF regimen in C. elegans induces OEA, which in turn lead to satiety followed by lipolysis and ATP synthesis. Lipolysis is stimulated by the increase in Adipose Tissue Triglyceride Lipase-1 (ATGL-1) activity that results from the enrichment in OEA precursor. In addition, the TRIF regimen induces oxidative stress resistance in C. elegans. Subsequently, this promotes longevity and slow aging in C. elegans by altering the insulin/ insulin-like growth factor signaling (IIS) pathway. The present study suggested the beneficial effects of time-restricted fasting in the eukaryotic model nematodes through the activation of lipid metabolism that involves enhanced production of OEA precursors which promotes lipolysis. In addition, the data revealed that the increased ATP production resulted in oxidative stress tolerance that promoted longevity and slow aging processes.

Keywords:   C. elegans ; GC-MS analysis; Lipolysis; Longevity; Oleic acid; Time- Restricted Intermittent Fasting

DOI:  https://doi.org/10.1007/s13105-025-01087-6
Stem Cell Res Ther. 2025 May 09. 16(1): 231

Terpenes: natural compounds found in plants as potential senotherapeutics targeting senescent mesenchymal stromal cells and promoting apoptosis.

Valeria Mazzone, Nicola Alessio, Domenico Aprile, Giovanni Galano, Roberto De Rosa, Chiara Schiraldi, Giovanni Di Bernardo, Umberto Galderisi.

   BACKGROUND: Senescence in stem cells and progenitor cells can be particularly detrimental because these cells are essential for tissue renewal and overall organismal homeostasis. In mesenchymal stromal cells (MSCs), which comprise a heterogeneous mix of stem cells, progenitors, fibroblasts, and other stromal cells, senescence poses a significant challenge, as it impairs their ability to support tissue repair and maintenance. This decline in regenerative capacity can contribute to aging-related diseases, impaired wound healing, and degenerative disorders. One hallmark of senescence is resistance to apoptosis, mediated by activation of anti-apoptotic pathways. Consequently, senotherapeutics have emerged as a promising strategy to selectively eliminate senescent cells and promote healthy aging. Plant secondary metabolites, notably polyphenols and terpenes, exhibit diverse effects on living organisms and have served as medicinal agents.
METHODS: In this study, we investigated four terpenes-carvacrol, thymol, eugenol, and lycopene-for their senolytic potential in human senescent MSCs.
RESULTS: We found that these compounds induce apoptosis through both caspase-dependent and caspase-independent mechanisms, involving the activation of BAX, cytochrome c release, and translocation of apoptosis-inducing factor (AIF) from mitochondria to nuclei. Importantly, terpene-induced apoptosis was associated with a significant increase in reactive oxygen species, and pre-incubation with glutathione partially rescued cell viability, confirming oxidative stress as a central trigger. Moreover, we identified SRC pathway modulation as a critical determinant of the senescence-to-apoptosis shift, highlighting a key regulatory switch in terpene action.
CONCLUSIONS: These findings provide a detailed mechanistic dissection of terpene-induced senolysis and underscore their potential as promising candidates for senotherapeutics targeting senescent cells.

Keywords:  Apoptosis; Mesenchymal stromal cells; Senescence; Senolytics; Terpenes

DOI:  https://doi.org/10.1186/s13287-025-04310-9
Skin Res Technol. 2025 Feb-May;31(2-5):31(2-5): e70162

Short- and Long-Term Effects of Adding Topical Cosmetics to a Dermatological Procedure (Thermage): A Randomized Controlled Comparative Study Exploring the Synergistic Effects.

Sae-Ra Park, Ji-Yei Choi, Jangmi Suk, Byung-Fhy Suh, Eunjoo Kim.

   BACKGROUND: Dermatological procedures improve skin changes caused by aging. However, few studies have focused on the effect of improving various skin characteristics compared with the concurrent use of cosmetics. We aimed to confirm changes in skin characteristics owing to anti-aging dermatological procedures in the short- and long-term and to determine the efficacy of the procedure when products with anti-aging and repair effects are used together.
MATERIALS AND METHODS: We included 42 women (mean age, 47.667 ± 3.183 years) divided into a test (n = 21) and control (n = 21) group, with no history of dermatological procedures within 3 months of the test participation date. The dermatological procedure involved a single application of Thermage treatments, and products containing repair and anti-aging ingredients were used for the test group. The skin changes were assessed using device-based measurements and image analysis up to 4 weeks post-procedure.
RESULTS: Post-procedure side effects were alleviated 1 day after the procedure, and transepidermal water loss (TEWL) improved when the products were used together. Skin hydration, elasticity, density, fine lines, texture, and pores improved at 4 weeks after the procedure. When the test product was also used, the improvement was significantly greater, and TEWL of the face improved in the test group only. Aging-related skin characteristics were improved by Thermage, and the combined use of test products and procedures with repair and anti-aging effects improved skin characteristics.
CONCLUSION: Dermatological procedures and cosmetic products have internal and external anti-aging effects on the skin, respectively, resulting in synergy.

Keywords:  cosmetic procedure; moisturization; skin aging; skin barrier; skin physiology/structure; skin repair

DOI:  https://doi.org/10.1111/srt.70162
Am J Clin Nutr. 2025 May 06. pii: S0002-9165(25)00247-3. [Epub ahead of print]

Adherence to EAT-Lancet diet, biological aging and life expectancy in the UK Biobank: a cohort study.

Yang-Wei Cai, Jing-Wei Gao, Mao-Xiong Wu, Yi-Xiu Xie, Si You, Guang-Hong Liao, Zhi-Teng Chen, Pin-Ming Liu, Jing-Feng Wang, Yang-Xin Chen, Hai-Feng Zhang.

   BACKGROUND: The EAT-Lancet diet was proposed to nurture human health and support environmental sustainability. However, the interactions among EAT-Lancet diet, biological aging and life expectancy have not been explored.
OBJECTIVES: We aimed to investigate the associations of adherence to EAT-Lancet diet pattern with biological aging and life expectancy, as well as the potential modification effect of genetic susceptibility.
METHODS: Data from UK Biobank cohort study were analyzed. The EAT-Lancet diet index was calculated using 24-hour dietary recall data to assess the adherence to EAT-Lancet diet. Polygenic risk scores (PRSs) were constructed to evaluate genetic risk for biological aging. Multivariable linear regression and flexible parametric survival models were used to investigate the association of EAT-lancet diet index with biological aging acceleration and with residual life expectancy, respectively. Mediation analysis was used to identify potential mediators.
RESULTS: Among 141,562 included participants (56.02±7.94 years old, 45.12% male), those with higher adherence to the EAT-Lancet diet was significantly associated with a slower pace of biological aging (for Stubbendorff EAT-Lancet diet index: KDM-BA acceleration: -1.37 years, 95% CI: -1.51, -1.24; PhenoAge acceleration: -0.93 years, 95% CI: -1.00, -0.86; comparing extreme quartiles, both P<0.001). At age 45, participants with the highest adherence to the EAT-Lancet diet also gained 1.13 years life expectancy than those with the lowest adherence. Similar patterns were observed when we used the Knuppel EAT-Lancet diet index. Adiposity indices, particularly waist-to-height ratio, mediated 29.31-35.40% of this association. No significant interaction was found between EAT-Lancet diet and genetic risks. The protective effects remained robust in a series of sensitivity analyses and across different subgroups.
CONCLUSIONS: Adherence to EAT-lancet diet is linked to delayed biological aging and increased life expectancy, regardless of genetic predisposition. This suggests that promoting this sustainable dietary pattern could serve as a practical nutritional strategy for enhancing healthy longevity.

Keywords:  EAT-Lancet diet; biological aging; genetic risk; life expectancy; prevention

DOI:  https://doi.org/10.1016/j.ajcnut.2025.04.030
J Cosmet Dermatol. 2025 May;24(5): e70206

Clinical Case Study Investigating a Longevity Daily Serum for Japanese Women With Facial Skin Aging.

Mayumi Nomoto, Morgann Young, Tatiana Kononov, Alisar Zahr.

DOI: https://doi.org/10.1111/jocd.70206
Biosci Biotechnol Biochem. 2025 May 08. pii: zbaf065. [Epub ahead of print]

Lactiplantibacillus brownii strain MH-1 prolongs healthspan and improves stress resistance in Caenorhabditis elegans.

Mina Hashimoto, Yoshihiko Tanimoto, Eriko Kage-Nakadai.

  Lactiplantibacillus brownii was first discovered in 2023. We previously isolated L. brownii strain MH-1 from homemade pickled Chinese cabbage in Hiroshima Prefecture, Japan, and performed whole-genome sequencing. In this study, we examined the beneficial effects of L. brownii strain MH-1 on a host using C. elegans. MH-1 and heat-killed MH-1 extended the lifespan and also alleviated motility decline during aging in worms. Feeding MH-1 to nematodes indicated its presence in the intestinal tract with no change in body or brood sizes, suggesting that dietary restrictions did not occur. There were no significant differences in intestinal barrier enhancement or fat accumulation in MH-1-fed C. elegans. The stress response of C. elegans was enhanced by MH-1 for oxidative stress tolerance. MH-1 increased the expression of genes involved in defense response and lipid catabolism. These results demonstrate the beneficial effects of MH-1 on nematodes and its potential use as a probiotic.

Keywords:  caenorhabditis elegans; healthspan; lactiplantibacillus brownii; motility; oxidative stress resistance

DOI:  https://doi.org/10.1093/bbb/zbaf065
Aging (Albany NY). 2025 May 05. 17

Methylation clocks for evaluation of anti-aging interventions.

Josh Mitteldorf.

  Methylation clocks have found their way into the community of aging research as a way to test anti-aging interventions without having to wait for mortality statistics. But methylation is a primary means of epigenetic control, and presumably has evolved under strong selection. Hence, if methylation patterns change consistently at late ages it must mean one of two things. Either (1) the body is evolved to destroy itself (with inflammation, autoimmunity, etc.), and the observed methylation changes are a means to this end; or (2) the body detects accumulated damage, and is ramping up repair mechanisms in a campaign to rescue itself. My thesis herein is that both Type 1 and Type 2 changes are occurring, but that only Type 1 changes are useful in constructing methylation clocks to evaluate anti-aging interventions. This is because a therapy that sets back Type 1 changes to an earlier age state has stopped the body from destroying itself; but a therapy that sets back Type 2 changes has stopped the body from repairing itself. Thus, a major challenge before the community of epigenetic clock developers is to distinguish Type 2 from Type 1. The existence of Type 1 epigenetic changes is in conflict with conventional Darwinian thinking, and this has prompted some researchers to explore the possibility that Type 1 changes might be a form of stochastic epigenetic drift. I argue herein that what seems like directed epigenetic change really is directed epigenetic change. Of five recent articles on "stochastic methylation clocks," only one (from the Conboy lab) is based on truly stochastic changes. Using the Conboy methodology and a methylation database, I construct a measure of true methylation drift, and show that its correlation with age is too low to be useful.

Keywords:  aging clock; entropy; epigenetic clock; methylation; programmed aging; stochastic

DOI:  https://doi.org/10.18632/aging.206245
Food Funct. 2025 May 06.

Multi-omics analysis reveals the attenuation effect of C-phycocyanin on aging-induced subfertility in female mice.

Zhe Han, Xin Wen, Lei Ge, Cheng-Jie Zhou, Dui Sun, Qi Yang, Fang-Rui Xue, Kang Ding, Cheng-Guang Liang.

Excessive inflammatory responses within the ovary are one of the main causes of subfertility in elderly women. Eliminating these responses can reverse fertility in aged individuals. Here, we demonstrate that administering 300 mg kg-1 day-1 C-phycocyanin (PC) to 36-week-old female mice for 45 days can reduce age-related fertility decline, resulting in an increase in litter size from 7.53 to 10.90. PC administration in aged mice enhances ovarian antioxidant enzyme levels, promotes first polar extrusion, and supports early embryonic development. Additionally, PC increases the proportion of normal spindle-chromosome complexes, normalizes mitochondrial distribution, reduces ROS levels, and decreases early apoptosis in aged mice. Notably, PC intervention mitigates age-related changes in gut microbiota composition, serum metabolite profiles, and ovarian gene expression patterns. Mechanistically, PC exerts its effects by suppressing interferon-γ expression, attenuating interferon responses, and preventing ovarian fibrosis, thereby improving reproductive function in aged female mice. Collectively, these findings highlight PC as a potential therapeutic agent to counter age-related fertility decline through targeted anti-inflammatory mechanisms.

DOI: https://doi.org/10.1039/d5fo00344j
J Cosmet Dermatol. 2025 May;24(5): e70210

Clinical Evaluation of an Innovative CaHA Bio-Stimulator in Facial Rejuvenation: 1 Year Follow-Up.

Giseli Petrone, Caroline Leão, Danilo Morais, Eliza Ducati, Matheus Kasai, Renata Viana.

   BACKGROUND: Skin aging is characterized by wrinkles, loss of elasticity, laxity, and rough texture, resulting from degenerative changes in the skin's layers. Effective treatments targeting skin structure are increasingly sought after in aesthetic medicine.
AIMS: This study aimed to evaluate the safety, efficacy, and long-term outcomes of STIIM, a novel calcium hydroxylapatite (CaHA)-based bio-stimulator, in facial rejuvenation.
PATIENTS/METHODS: Thirty-two patients aged 35-59 received diluted CaHA injections. Outcomes were assessed through patient satisfaction surveys and objective measurements, including ultrasound evaluation of dermal thickness. Follow-ups were conducted at 120 and 360 days post-procedure. Safety was evaluated by monitoring adverse events.
RESULTS: At 120 days post-treatment, 85% of patients reported visible aesthetic improvements, and ultrasound assessments in a subset of patients demonstrated a significant 51% increase in dermal thickness, indicating improved skin structure. At 360 days, 75% of the patients continued to report aesthetic benefits, confirming the durability of the results. The treatment was well-tolerated, with no serious adverse events reported throughout the study period.
CONCLUSIONS: This novel CaHA-based bio-stimulator demonstrates a safe and effective profile for facial rejuvenation, providing significant aesthetic and structural improvements with long-lasting results. It offers a promising option for addressing the challenges of skin aging.

Keywords:  calcium hydroxilapatite; patient satisfaction; skin laxity

DOI:  https://doi.org/10.1111/jocd.70210
Clin Exp Immunol. 2025 May 08. pii: uxaf029. [Epub ahead of print]

Senolytic treatment to rescue hallmarks of senescence in lymph node fibroblasts from patients with rheumatoid arthritis: Implications for premature aging and potential therapeutic intervention in early rheumatoid arthritis.

T A de Jong, J F Semmelink, J W Bolt, C Grasso, R A Hoebe, P M Krawczyk, L G M van Baarsen.

   INTRODUCTION: Cellular senescence, a state of proliferation arrest, is implicated in the pathogenesis of age-related diseases such as rheumatoid arthritis (RA). The pathogenesis of RA, characterized by immune dysregulation and systemic autoimmunity preceding clinical onset of disease, may involve early accumulation of senescent lymph node (LN) fibroblasts driving immune tolerance breakdown. This study aims to explore the hallmarks of senescence in LN fibroblasts during the earliest phases of RA and evaluate the effects of dasatinib.
METHODS: Human LN fibroblasts were isolated from inguinal LN needle biopsies from autoantibody-positive individuals at risk of developing RA (RA-risk individuals), RA patients and seronegative healthy volunteers. Senescence hallmarks and the effects of dasatinib treatment were assessed using quantitative PCR, flow cytometry, microscopy, and live-cell imaging.
RESULTS: Cell size, granularity and autofluorescence were significantly greater in RA LN fibroblasts compared with controls. Altered gene expression of senescence-associated genes was observed in RA LN fibroblasts. Elevated senescence-associated β-galactosidase activity, more lipofuscin-positive granules and DNA damage were observed in RA-risk and RA LN fibroblasts. Notably, RA(-risk) LN fibroblasts presented impaired DNA damage repair capacity. Dasatinib treatment significantly improved the size and ability of the LN fibroblast pool to repair DNA damage. We observed multiple senescence hallmarks in RA LN fibroblasts and, to a lesser extent, in RA-risk LN fibroblasts, which could be partially restored by senescent cell removal via dasatinib treatment.
CONCLUSION: These findings suggest a role for senescent LN fibroblasts in RA pathogenesis and highlights the potential of dasatinib as a potential therapeutic intervention to mitigate senescence-associated defects in RA.

Keywords:  Autoimmunity; RA-risk individuals; lymph node fibroblasts; senescence

DOI:  https://doi.org/10.1093/cei/uxaf029
Eur J Transl Myol. 2025 May 08.

Longevity concept by regenerative medicine methods synergy: exosome therapy, functional medicine, and advanced multi-wavelengths laser therapy.

Yasaman Zandi Mehran, Hans Michael Weber, Fateme Hoseinzade, Nahid Tafazoli Harandi, Mozhgan Ayazi, Shila Mirzadeh.

Regenerative medicine is one of the most important branches of medicine today and in the future and brings together all the methods to stop or even reverse the aging process. Regenerative medicine may include cellular therapies such as stem cell therapy or extracellular vesicle therapies such as exosomes and growth factor therapy. It may also involve the use of Photobiomodulation (PBM) and functional medicine treatments targets on mitochondrial medicine, to control the aging process. In this article, we have discussed the role, importance, rationale, overlap, and synergy of the joint application of these methods. Combining these regenerative medicine approaches can achieve better results in various medical indications. For longevity, any autoimmune disease, chronic disease, especially in elderly patients, this recommended combination seems to be very critical, for a higher survival rate in cell therapy methods. It is like a plant growing process that requires good quality seeds (cell therapy), light (targeted laser therapy) and good soil (functional medicine).

DOI: https://doi.org/10.4081/ejtm.2025.13540
Mech Ageing Dev. 2025 May 03. pii: S0047-6374(25)00045-4. [Epub ahead of print] 112069

Role of Stem Cells in Ageing and Age-related Diseases.

Jitendra Kumar Chaudhary, Ajay Kumar Danga, Anita Kumari, Akshay Bhardwaj, Pramod C Rath.

  Stem cell functions and ageing are deeply interconnected, continually influencing each other in multiple ways. Stem cells play a vital role in organ maintenance, regeneration, and homeostasis, all of which decline over time due to gradual reduction in their self-renewal, differentiation, and growth factor secretion potential. The functional decline is attributed to damaging extrinsic environmental factors and progressively worsening intrinsic genetic and biochemical processes. These ageing-associated deteriorative changes have been extensively documented, paving the way for the discovery of novel biomarkers of ageing for detection, diagnosis, and treatment of age-related diseases. Age-dependent changes in adult stem cells include numerical decline, loss of heterogeneity, reduced self-renewal and differentiation, leading to a drastic reduction in regenerative potential, and thereby drive the ageing process. Conversely, ageing also adversely alters the stem cell niche, disrupting the molecular pathways underlying stem cell homing, self-renewal, differentiation, and growth factor secretion, all of which are critical for tissue repair and regeneration. A holistic understanding of these molecular mechanisms, through empirical research and clinical trials, is essential for designing targeted therapies to modulate ageing and improve health parameters in older individuals.

Keywords:  Ageing; Clinical Trials; Differentiation; Regeneration; Self-renewal; Stem Cells

DOI:  https://doi.org/10.1016/j.mad.2025.112069
Curr Top Med Chem. 2025 Apr 30.

The Effects of Plasma Exosomes of Young Individuals Compared to Old Ones on Age-Related Inflammation and Lineage Differentiation of CD34+ Umbilical Cord Blood Hematopoietic Stem Cells.

Maryam Helali, Saeid Kaviani, Shaban Alizadeh, Reza Afrisham, Mohammad Ahmadvand.

   INTRODUCTION: Cellular aging is a complicated event known for gradually reducing homeostasis, leading to a higher susceptibility to diseases and mortality. Since the behavior of Hematopoietic Stem Cells (HSCs) is potentially affected by plasma-derived exosomes, this study aimed to investigate whether the plasma-derived exosome of young and elderly human donors can deliver "youth" or "aging" signals into human umbilical cord blood-derived HSCs in vitro.
METHODS: Exosomes were isolated from four young (Y-exo) and four old (O-exo) donors. Umbilical cord blood-derived HSCs were exposed to two concentrations of exosomes (5 and 10 μg/mL). Then, lineage differentiation (CD41 and CD38), the mRNA and protein expression of IL-1β and IL- 6, and NFκB activity were evaluated using flow cytometry, qRT-PCR Enzyme-Linked Immunosorbent Assay (ELISA) methods, and western blot techniques, respectively.
RESULTS: The lineage-specific markers CD41 and CD38 expression were increased after exposure to O-exo compared to Y-exo at the concentration of 10 μg/mL (P<0.001). The HSCs treated with 10 μg/mL O-exo increased protein and mRNA expression of IL-1β and IL-6 compared to Y-exo at 10 μg/mL concentration (P<0.01). Furthermore, a significant difference was seen in p-NF-κB levels between O-exo and Y-exo at the concentration of 10 μg/mL (P=0.0014).
CONCLUSION: Our findings advocated the concept that circulating exosomes of old and young individuals may differently affect the pathways involved in the aging process in HSCs.Therefore, exosomes may be applied as therapeutic agents for regenerative medicine.

Keywords:  Exosomes; aging; differentiation.; hematopoietic stem cells; inflammation

DOI:  https://doi.org/10.2174/0115680266361607250418052405