bims-caglex 2025-05-04 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2025–05–04
34 papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

Age reprogramming: Innovations and ethical considerations for prolonged longevity (Review).
Astragalus Membranaceus-Can It Delay Cellular Aging?
Elucidating the Role and Mechanism of Alpha-Enolase in Senescent Amelioration via Metabolic Reprogramming.
Single-cell profiling unveils a geroprotective role of Procyanidin C1 in hematopoietic immune system via senolytic and senomorphic effects.
Umbilical Cord Blood Plasma Enhances Cellular Repair and Senescence Suppression in Human Dermal Fibroblasts Under Oxidative Stress.
Neuronal C/EBPβ Shortens the Lifespan via Inactivating NAMPT.
The Probiotic Yeast, Milmed, Promotes Autophagy and Antioxidant Pathways in BV-2 Microglia Cells and C. elegans.
Aqueous Polygalae Radix extract (PRE) prolongs the lifespan of C. elegans and alleviates D-galactose-induced oxidative stress in the mouse liver and brain by modulating PPARγ/MAPK.
Procyanidin C1 ameliorates aging-related skin fibrosis through targeting EGFR to inhibit TGFβ/SMAD pathway.
Aging and Lifestyle Modifications for Preventing Aging-Related Diseases.
ABT263 Ameliorates Cellular Senescence, Aβ-Dependent Pathology and Cognitive Decline in Aged APP/PS1 Mice via Regulating PI3K/AKT/GSK-3β Pathways.
Synthetic and Natural Agents Targeting Advanced Glycation End-Products for Skin Anti-Aging: A Comprehensive Review of Experimental and Clinical Studies.
Enterococcus faecalis SI-FC-01 enhances the stress resistance and healthspan of C. elegans via AKT signaling pathway.
Leaf miRNAs of Withania somnifera Negatively Regulate the Aging-Associated Genes in C. elegans.
Delaying liver aging: Analysis of structural and functional alterations.
Cdkn1a silencing restores myoblast differentiation by inducing selective apoptosis in senescent cells.
Inhibition of CD45-specific phosphatase activity restores the differentiation potential of aged mesenchymal stromal cells: implications in regenerative medicine.
Is Senolytic Therapy in Cardiovascular Diseases Ready for Translation to Clinics?
Plasma Extracellular Vesicle-Derived miR-296-5p is a Maturation-Dependent Rejuvenation Factor that Downregulates Inflammation and Improves Survival after Sepsis.
Taurine ameliorates cellular senescence associated with an increased hydrogen sulfide and a decreased hepatokine, IGFBP-1, in CCl4-induced hepatotoxicity in mice.
Click Chemistry-Assisted Rejuvenation of Aging T Cells Sensitizes Aged Mice to Tumor Immunotherapy.
Unlocking regeneration: how partial reprogramming resembles tissue healing.
Gui-Pi-Tang Defers Skeletal Muscle and Cardiac Muscle Aging by Promoting Mitochondrial Remodeling.
Polydatin reactivates mitochondrial bioenergetics and mitophagy while preventing premature senescence by modulating microRNA-155 and its direct targets in human fibroblasts with trisomy 21.
Multidomain intervention for delaying aging in community-dwelling older adults (MIDA): study design and protocol.
Current Approaches in Cosmeceuticals: Peptides, Biotics and Marine Biopolymers.
Evaluation and Treatment Planning to Maximize Perioral, Submental, and Neck Aesthetics.
Evaluating the Efficacy of Acupotomy Subcision and Hyaluronic Acid Injections for Neck Wrinkles: A Randomized Trial.
Inhibition of GSK-3β Restores Differentiation Potential of Late-Passage Mesenchymal Stem Cells.
Stem cells as role models for reprogramming and repair.
Exercise Mimetics in Aging: Suggestions from a Systematic Review.
Identifying Age-Modulating Compounds Using a Novel Computational Framework for Evaluating Transcriptional Age.
Alhagi camelorum seed polysaccharide alleviates methylglyoxal-induced skin damage via antioxidant and anti-inflammatory actions.
Investigating the Effects of a Manuka Honey, Royal Jelly, and Bee Venom-Derived Face Serum on Skin Health and Signs of Aging.

Biomed Rep. 2025 Jun;22(6): 96

Age reprogramming: Innovations and ethical considerations for prolonged longevity (Review).

Timur Saliev, Prim B Singh.

  Age reprogramming and cellular rejuvenation therapies are revolutionizing the approach to aging and age-related diseases. These ground-breaking interventions target fundamental biological processes, including genomic instability, telomere attrition, and mitochondrial dysfunction, to restore cellular function and delay the onset of degenerative conditions. Emerging strategies such as epigenetic reprogramming, gene editing, stem cell therapy, and senolytic drugs show immense promise in extending health spans and potentially reversing aspects of aging. Despite marked progress in preclinical studies and early-stage clinical trials, translating these therapies into practical healthcare solutions presents significant challenges. Key issues include ensuring safety, optimizing delivery mechanisms, overcoming regulatory barriers, and addressing high costs. Moreover, ethical and economic considerations, such as equitable access and societal impacts, must be carefully addressed to prevent widening health disparities. The present review examines the current state of cellular rejuvenation research, highlighting both scientific advancements and the complex challenges associated with these therapies. With interdisciplinary collaboration, robust ethical frameworks, and scalable technological innovations, these therapies have the potential to transform healthcare. By shifting the focus from disease management to proactive health preservation, they offer a future where aging becomes a manageable and equitable process.

Keywords:  CRISPR; age reprogramming; epigenetic; ethics; gene editing; rejuvenation; senolytics; stem cell therapy

DOI:  https://doi.org/10.3892/br.2025.1974
Nutrients. 2025 Apr 08. pii: 1299. [Epub ahead of print]17(8):

Astragalus Membranaceus-Can It Delay Cellular Aging?

Kinga K Borowicz, Monika E Jach.

  Astragalus membranaceus, a plant that has been utilized in traditional Chinese medicine for centuries, is widely regarded as one of the most valuable herbs in this medicinal tradition. It is commonly referred to as the "yellow leader", a designation that stems from the yellow hue of its most significant organ, the root, and its adaptogenic properties. The plant Astragalus is renowned for its abundance of active components, including polysaccharides, flavonoids, saponins, and an array of trace elements. It has been demonstrated that the administration of Astragalus can prevent cellular aging, owing to its diverse range of actions that provide protection to the body from both external and internal factors. The antioxidant, immunomodulatory, anti-inflammatory, and regenerative properties of this plant contribute to the maintenance of good skin condition, preventing atrophy of subcutaneous tissue and degeneration of facial bones. Systemic actions encompass the maintenance of function and protection of the cardiovascular, nervous, respiratory, digestive, excretory, immune, and endocrine systems. This article reviews the composition of Astragalus membranaceus and the beneficial effects of its root extract and its active substances on the whole body, with a particular focus on the anti-aging effects on the skin.

Keywords:  Astragalus membranaceus; anti-aging effects; cellular senescence; skin aging; systemic aging

DOI:  https://doi.org/10.3390/nu17081299
Cell Prolif. 2025 Apr 27. e70049

Elucidating the Role and Mechanism of Alpha-Enolase in Senescent Amelioration via Metabolic Reprogramming.

Yun Haeng Lee, Hyunwoong Lim, Gyungmin Kim, Geonhee Jang, Myeong Uk Kuk, Ji Ho Park, Jee Hee Yoon, Yoo Jin Lee, Duyeol Kim, Byeonghyeon So, Minseon Kim, Hyung Wook Kwon, Youngjoo Byun, Joon Tae Park.

  Senescent cells are characterised by increased glycolysis dependence. Normalisation of glycolysis metabolism is essential for senescence amelioration. However, the mechanism of proteins involved in cellular glycolysis metabolism has not been fully elucidated. Here, we identified a candidate compound, an oxazole analogue (KB2764), that can improve senescence. To elucidate the mechanism of the KB2764, we investigated the interacting proteins. KB2764 interacted with alpha-enolase (ENO1) and pyruvate kinase M (PKM), ultimately allowing PKM to phosphorylate ENO1. KB2764 consequently increased mitochondrial ATP production and reduced reliance on glycolysis. Knockdown of the ENO1 experiment in senescent cells demonstrates that regulation of ENO1 activity is a prerequisite for recovery of mitochondrial function. Furthermore, the action of KB2764 extends its application to extend the lifespan of Caenorhabditis elegans. Taken together, our findings reveal a novel mechanism by which senescence is ameliorated through metabolic reprogramming and mitochondrial functional recovery via KB2764-mediated regulation of ENO1 protein activity.

Keywords:   Caenorhabditis elegans ; alpha‐enolase; metabolic reprogramming; senescence amelioration

DOI:  https://doi.org/10.1111/cpr.70049
NPJ Aging. 2025 May 02. 11(1): 31

Single-cell profiling unveils a geroprotective role of Procyanidin C1 in hematopoietic immune system via senolytic and senomorphic effects.

Xiuxing Liu, Yidan Liu, Yuehan Gao, Chun Zhang, Chenyang Gu, Jianjie Lv, Junying Wu, Wenru Su.

Aging of hematopoietic and immune system (HIS) leads to cellular senescence and immune dysregulation, contributing to age-related diseases. Here, we show that Procyanidin C1 (PCC1), a compound with both senolytic and senomorphic properties, can counteract aging-related changes in HIS. Using single-cell RNA sequencing and validation experiments, we found that aging induced cellular senescence, inflammation, and immune dysregulation in the bone marrow and spleen tissues of mice. Long-term PCC1 treatment improved key physiological parameters especially the grip strength of aged mice. Further single-cell analysis revealed PCC1's broad geroprotective effects on HIS, including an increase in the proportion of B cells (BCs) and hematopoietic stem cells (HSCs), suppression of senescence-associated markers, and restoration of normal immune processes. Specifically, PCC1 mitigated inflammation and restored immune homeostasis in BCs by suppressing Cebpb expression and age-associated BCs. Moreover, PCC1 reversed aging-induced alterations in HSCs through upregulating Nedd4 and CD62L-Ca2+ axis expression. Finally, we identified senescent cells (SnCs) using machine learning and gene set enrichment analysis, revealing that PCC1 induced apoptosis of SnCs and regulated their metabolic processes, particularly in granulocytes and myeloid cells. The experimental validation further confirmed the senolytic and senomorphic effects of PCC1 both in vivo and in vitro. Overall, PCC1 holds potential as a therapeutic agent for alleviating immune dysfunction and promoting healthy aging via senolytic and senomorphic effects.

DOI: https://doi.org/10.1038/s41514-025-00222-3
Rejuvenation Res. 2025 May 02.

Umbilical Cord Blood Plasma Enhances Cellular Repair and Senescence Suppression in Human Dermal Fibroblasts Under Oxidative Stress.

Miso Jeong, Hyangju Lee, Tae-Hyun Ko, Soo Jin Choi, Wonil Oh, Sangwoo Kim.

  Aging is associated with a gradual decline in cellular function, largely driven by oxidative stress, which leads to cellular senescence. These processes contribute to tissue degeneration and age-related dysfunction. Human dermal fibroblasts (HDFs), critical for maintaining skin structure, are highly vulnerable to oxidative damage, making them key contributors to skin aging. Umbilical cord blood plasma (UCBP), rich in growth factors and regenerative molecules, has shown potential in preventing cellular senescence and addressing key mechanisms of tissue aging. Based on findings from heterochronic parabiosis experiments that demonstrated the rejuvenating effect of young blood, we investigated the effects of UCBP on hydrogen peroxide (H2O2) induced oxidative stress in HDFs and compared its efficacy with adult blood plasma (ABP). Our results indicate that although both UCBP and ABP reduce reactive oxygen species (ROS), UCBP is more effective in suppressing cellular senescence and maintaining fibroblast proliferation. These findings suggest that UCBP's protective effects extend beyond ROS reduction, potentially by modulating the senescence-associated secretory phenotype and the enhancement of tissue repair mechanisms.

Keywords:  cellular senescence; fibroblast proliferation; oxidative stress; umbilical cord blood plasma

DOI:  https://doi.org/10.1089/rej.2024.0085
Adv Sci (Weinh). 2025 Apr 30. e2414871

Neuronal C/EBPβ Shortens the Lifespan via Inactivating NAMPT.

Bowei Li, Zhongyun Xie, Mengmeng Wang, Shuke Nie, Zhengjiang Qian, Xin Meng, Xia Liu, Seong Su Kang, Keqiang Ye.

  The brain plays a central role in aging and longevity in diverse model organisms. Morphological and functional alteration in the aging brain elicits age-associated neuronal dysfunctions. However, the primary mechanism deteriorating the brain functions to regulate the aging process remains incompletely understood. Here, it is shown that neuronal CCAAT/enhancer binding protein β (C/EBPβ) escalation during aging dictates the frailty and lifespan via inactivating nicotinamide phosphoribosyltransferase (NAMPT). Upregulated C/EBPβ drives neuronal senescence and neuronal loss, associated with NAMPT fragmentation by active asparagine endopeptidase (AEP), leading to nicotinamide adenine dinucleotide (NAD+) depletion. Knockout of AEP or expression of AEP-resistant NAMPT N136A mutant significantly elongates the lifespan of neuronal-specific Thy 1-C/EBPβ transgenic mice. Overexpression of the C. elegans C/EBPβ ortholog cebp-2 in neurons shortens lifespan and decreases NAD+ levels, which are restored by feeding nicotinamide mononucleotide (NMN) or AEP inhibitor #11a. Feeding NMN or #11a substantially ameliorates the cognitive and motor impairments of Thy 1-C/EBPβ mice and increases the life expectancy. Notably, #11a demonstrates a better therapeutic effect than NMN in improving aging phenotype in Thy 1-C/EBPβ transgenic mice, which show accelerated aging features. Hence, blockade of AEP via therapeutic intervention may provide an unprecedented strategy for fighting aging and various age-associated diseases.

Keywords:  CCAAT/enhancer binding protein β (C/EBPβ); asparagine endopeptidase (AEP); brain aging; nicotinamide adenine dinucleotide (NAD+); nicotinamide phosphoribosyltransferase (NAMPT)

DOI:  https://doi.org/10.1002/advs.202414871
Antioxidants (Basel). 2025 Mar 27. pii: 393. [Epub ahead of print]14(4):

The Probiotic Yeast, Milmed, Promotes Autophagy and Antioxidant Pathways in BV-2 Microglia Cells and C. elegans.

Federica Armeli, Beatrice Mengoni, Emily Schifano, Thomas Lenz, Trevor Archer, Daniela Uccelletti, Rita Businaro.

  Background: Autophagy, a catabolic process essential for maintaining cellular homeostasis, declines with age and unhealthy lifestyles, contributing to neurodegenerative diseases. Probiotics, including Milmed yeast, have demonstrated anti-inflammatory and antioxidant properties. This study evaluated the activity of Milmed on BV-2 microglial cells in vitro and in the in vivo model of Caenorhabditis elegans (C. elegans) in restoring autophagic processes. Methods: BV-2 microglial cells were incubated with S. cerevisiae (Milmed treated yeast or untreated yeast) and then stimulated with lipopolysaccharide (LPS). mRNAs of the autophagic factors and antioxidant enzymes were assessed by qPCR; mTOR and NRF2 were evaluated by ELISA. pNRF2 compared with cytosolic NRF2 was evaluated by immunofluorescence. The longevity, body size, and reactive oxygen species (ROS) levels of C. elegans were measured by fluorescence microscopy. Results: Treatment with Milmed YPD cultured yeast or the dried powder obtained from it promoted autophagic flux, as shown by the increased expression of the Beclin-1, ATG7, LC3, and p62 mRNAs and the inhibition of mTOR, as evaluated by ELISA. It also enhanced the antioxidant response by increasing the expression of NRF2, SOD1, and GPX; moreover, pNRF2 expression compared with cytosolic NRF2 expression was enhanced, as shown by immunofluorescence. Milmed dietary supplementation prolonged the survival of C. elegans and reduced the age-related ROS accumulation without changing the expression of gst-4. The pro-longevity effect was found to be dependent on SKN-1/Nrf2 activation, as shown by the absence of benefit in skn-1 mutants. Conclusions: Milmed yeast demonstrates significant pro-autophagy and antioxidant activity with significant pro-longevity effects in C. elegans, thereby extending the lifespan and improving stress resistance, which, together with the previously demonstrated anti-inflammatory activity, highlights its role as a highly effective probiotic for its beneficial health effects. Activation of the SKN-1/NRF2 pathway and the modulation of autophagy support the therapeutic potential of Milmed in neuroprotection and healthy aging.

Keywords:  Caenorhabditis elegans; NRF2; ROS; autophagy; longevity; microglia; neuroinflammation; oxidative stress; probiotic; yeast

DOI:  https://doi.org/10.3390/antiox14040393
J Ethnopharmacol. 2025 Apr 24. pii: S0378-8741(25)00562-8. [Epub ahead of print]348 119878

Aqueous Polygalae Radix extract (PRE) prolongs the lifespan of C. elegans and alleviates D-galactose-induced oxidative stress in the mouse liver and brain by modulating PPARγ/MAPK.

Jiaqi Zhang, Wenxue Zheng, Zhengjie Zhou, YiMing An, Haoyu Zheng, Yanan Zhang, Yuchen Wei, Qianhua Zhang, Jingtong Zheng, Fang Wang.

   ETHNOPHARMACOLOGICAL RELEVANCE: Polygalae Radix has high pharmacological activity and has been widely used as a sedative and tranquilizer to increase cognitive function, prevent epilepsy, and treat respiratory diseases such as bronchitis. However, its role in delaying aging and decreasing oxidative stress and its main functional factors have not been thoroughly studied.
AIM OF THE STUDY: The purpose was to investigate the antiaging and antioxidant effects of aqueous Polygalae Radix extract (PRE) and its mechanism of action.
MATERIALS AND METHODS: The effects of different concentrations (1, 5, and 10 mg/mL) of PRE on the lifespan, body length, reproductive ability, motility, lipofuscin, and reactive oxygen species (ROS) on a model of natural senescence of Caenorhabditis elegans were investigated. The effects of PRE treatment on the expression of body weight, malondialdehyde (MDA), glutathione peroxidase (GSH-PX), and mTERT content were evaluated in a D-galactose (Dgal)-induced mouse model of aging. Histopathological changes in the liver and brain of mice were analyzed by hematoxylin-eosin (HE). The enriched pathways associated with differentially expressed genes in the liver tissues of C. elegans and mice were analyzed via RNA-seq, and the results were verified via RT-qPCR, cell transfection and Western blotting. Abundance of and changes in the mouse intestinal flora were analyzed by 16S rDNA sequencing.
RESULTS: PRE significantly prolonged the average lifespan of C. elegans and improved the physiological indices related to senescence. In addition, PRE slowed the decrease in weight of senescent model mice; protected serum, liver and brain tissues from oxidative stress damage; increased GSH-PX expression; and reduced MDA expression. The role of PRE in the low- and middle-dose groups was similar to that of vitamin C (VC) in inhibiting oxidative stress, but the effect of PRE in the high-dose group was greater than that of VC. The RNA-seq results suggested that PRE might be related to PPARγ/MAPK, and the subsequent RT-qPCR and cell transfection results indicated that PRE decreased oxidative stress by downregulating the mRNA expression of the Fabp1, Acaa1b, Hmgcs1, Map3K5, and Rac2 genes. The Western blot results revealed that PRE decreased oxidative stress by increasing PPARγ expression and inhibiting p38 protein phosphorylation. 16S rDNA sequencing showed that PRE treatment increased the abundance of the intestinal flora in mice and inhibited the growth of pathogenic bacteria such as Helicobacter pylori and Desulfurization vibrio while promoting the growth of beneficial bacteria such as Bifidobacteria.
CONCLUSIONS: PRE delays aging and resists oxidative stress in organisms; it may act by regulating the PPARγ/MAPK signaling pathway and the intestinal flora. The efficacy and mechanism of PRE against oxidative stress were elucidated using RNA-seq and 16S rDNA sequencing, providing a reference for antiaging and aging-related diseases.

Keywords:  Antioxidant; Dgal; Intestinal flora; PPARγ/MAPK signaling pathway

DOI:  https://doi.org/10.1016/j.jep.2025.119878
Phytomedicine. 2025 Apr 24. pii: S0944-7113(25)00425-8. [Epub ahead of print]142 156787

Procyanidin C1 ameliorates aging-related skin fibrosis through targeting EGFR to inhibit TGFβ/SMAD pathway.

Jun-Han Wang, Min Li, Peng-Fei Xie, Jia-Yao Si, Zhen-Jie Feng, Chuan-Feng Tang, Jian-Mei Li.

   BACKGROUND: Aging-related skin fibrosis (SF) is a complex condition with limited treatment options. Procyanidin C1 (PCC1), a natural polyphenolic compound with demonstrated senolytic activity, has emerged as a potential therapeutic agent for fibrotic disorders through its selective elimination of senescent cells. However, its therapeutic efficacy and mechanisms in aging-related SF remain unclear.
PURPOSE: This study aimed to investigate the mechanisms of PCC1 in aging-related SF.
RESULTS: In D-galactose-induced L929 cells, PCC1 treatment significantly attenuated the expression of both senescence-associated markers (IL-1β, P16, P21 and LMNB1) and fibrosis-related markers (α-SMA, LOXL2 and COL1). Network pharmacology and experimental validation (molecular docking, DARTS, CETSA, MST) identified EGFR as a primary target, with PCC1 directly binding to and inhibiting EGFR phosphorylation. Furthermore, PCC1 treatment effectively down-regulated TGFβ1 expression and suppressed SMAD2/3 phosphorylation in D-galactose-induced L929 cells. Notably, PCC1 blocked NSC228155-induced EGFR phosphorylation and inhibited ERK/MAPK, AKT/mTOR and TGFβ/SMAD pathway activation. In bleomycin-induced SF mice, PCC1 significantly attenuated epidermal hyperplasia, improved collagen structure, restored the collagen I/III ratio, and reduced EGFR phosphorylation along with TGFβ1 expression and SMAD2/3 phosphorylation.
CONCLUSION: This study elucidates that PCC1 exerts its anti-fibrotic effects through dual mechanisms: resistance to cellular senescence and modulation of fibroblast heterogeneity. By directly binding to EGFR and inhibiting its phosphorylation, PCC1 subsequently suppresses multiple downstream signaling cascades, ultimately ameliorating TGFβ/SMAD-mediated SF. These findings establish PCC1 as a promising therapeutic candidate for aging-related skin fibrosis, offering a novel approach through targeted EGFR inhibition and comprehensive pathway modulation.

Keywords:  EGFR; Procyanidin C1; Senescent fibroblasts; Skin fibrosis; TGFβ/SMAD pathway

DOI:  https://doi.org/10.1016/j.phymed.2025.156787
FASEB J. 2025 May 15. 39(9): e70575

Aging and Lifestyle Modifications for Preventing Aging-Related Diseases.

Qiao Li, Heng Zhang, Nanyin Xiao, Guangyu Liang, Yan Lin, Xiao Yang, Jiankun Yang, Zonghao Qian, Yangguang Fu, Cuntai Zhang, Anding Liu.

  The pathogenesis of various chronic diseases is closely associated with aging. Aging of the cardiovascular system promotes the development of severe cardiovascular diseases with high mortality, including atherosclerosis, coronary heart disease, and myocardial infarction. Similarly, aging of the nervous system promotes the development of neurodegenerative diseases, such as Alzheimer's disease, which seriously impairs cognitive function. Aging of the musculoskeletal system is characterized by decreased function and mobility. The molecular basis of organ aging is cellular senescence, which involves multiple cellular and molecular mechanisms, such as impaired autophagy, metabolic imbalance, oxidative stress, and persistent inflammation. Given the ongoing demographic shift toward an aging society, strategies to delay or reduce the effects of aging have gained significance. Lifestyle modifications, such as exercise and calorie restriction, are now recognized for their anti-aging effects, their capacity to reduce modification, their potential to prolong lifespan, and their capacity to lower the risk of cardiovascular disease. This review elucidates the molecular mechanisms and application significance of various anti-aging approaches at the molecular level, based on research progress in aging. It aims to provide a reference for the prevention and treatment of age-related diseases in progressively aging societies.

Keywords:  aging; aging‐related diseases; cellular senescence; lifestyle modifications

DOI:  https://doi.org/10.1096/fj.202402797RR
Cell Biochem Biophys. 2025 Apr 28.

ABT263 Ameliorates Cellular Senescence, Aβ-Dependent Pathology and Cognitive Decline in Aged APP/PS1 Mice via Regulating PI3K/AKT/GSK-3β Pathways.

Zhi Tang, Xiao-Ling Wang, Yu-Xin Deng, Yan Xiao, Jian-Wei Xu, Li Wang, Xiao-Lan Qi.

  Alzheimer's disease is defined pathologically by the irregular buildup of senile plaques, neurofibrillary tangles, and associated neuroinflammation. As aging progresses, senescent cells gradually accumulate and significantly contribute to brain dysfunction; however, the precise mechanisms driving aging remain unclear. In the current study, ABT263, a potent senolytic drug, was administered orally to APP/PS1 mice (n = 16) for five days per cycle throughout the course of two cycles, and their behavioral tests in the Morris water maze were evaluated. Using mouse hippocampal tissue, senescence-related gene expression and SASP-associated protein expression were assessed using biochemical tests and immunohistochemical labeling. The Morris water maze test results indicated that ABT263 alleviated spatial memory impairment and reduced amyloid-β (Aβ) accumulation in APP/PS1 mice. Additionally, ABT263 treatment led to a decline in senescence-associated β-galactosidase activity, p16 senescence-related gene expression, and the expression of SASP-associated proteins, including IL-6, IL-8, and MMP-1. Further investigation revealed that ABT263 enhanced the phosphorylation levels of phosphatidylinositol-3 kinase (PI3K) (Tyr458), serine/threonine kinase AKT (S473), and glycogen synthase kinase-3β (GSK-3β) (Ser9) in APP/PS1 mice. Our results showed that ABT263 protected neurons against Aβ pathology, reduced the accumulation of senescent cells, and improved cognitive decline by enhancing PI3K/AKT/GSK-3 activity.

Keywords:  ABT263; Aβ; Cognitive deficit; Inflammation; PI3K/AKT/GSK-3β; Senescent cells

DOI:  https://doi.org/10.1007/s12013-025-01745-y
Antioxidants (Basel). 2025 Apr 20. pii: 498. [Epub ahead of print]14(4):

Synthetic and Natural Agents Targeting Advanced Glycation End-Products for Skin Anti-Aging: A Comprehensive Review of Experimental and Clinical Studies.

Joon Yong Choi, Nam Gyoung Ha, Weon Ju Lee, Yong Chool Boo.

  Advanced glycation end-products (AGEs) cause blood vessel damage and induce diabetic complications in various organs, such as the eyes, kidneys, nerves, and skin. As glycation stress causes aesthetic, physical, and functional changes in the skin, glycation-targeting skin anti-aging strategies are attracting attention in cosmetology and dermatology. The primary goal of this review is to understand the significance of glycation-induced skin aging and to examine the therapeutic potential of glycation-targeting strategies. This study covers experimental and clinical studies exploring various interventions to attenuate glycation-induced skin aging. Glycation stress decreases the viability of cells in culture media, the cell-mediated contraction of collagen lattices in reconstructed skin models, and the expression of fibrillin-1 at the dermo-epidermal junction in the skin explants. It also increases cross-links in tail tendon collagen in animals, prolonging its breakdown time. However, these changes are attenuated by several synthetic and natural agents. Animal and clinical studies have shown that dietary or topical administration of agents with antiglycation or antioxidant activity can attenuate changes in AGE levels (measured by skin autofluorescence) and skin aging parameters (e.g., skin color, wrinkles, elasticity, hydration, dermal density) induced by chronological aging, diabetes, high-carbohydrate diets, ultraviolet radiation, or oxidative stress. Therefore, the accumulating experimental and clinical evidence supports that dietary supplements or topical formulations containing one or more synthetic and natural antiglycation agents may help mitigate skin aging induced by AGEs.

Keywords:  advanced glycation end-products; anti-aging; antiglycation; antioxidant; cosmetics; dermatology; glycation inhibitor; phytochemical; plant extract; skin aging

DOI:  https://doi.org/10.3390/antiox14040498
Sci Rep. 2025 Apr 25. 15(1): 14454

Enterococcus faecalis SI-FC-01 enhances the stress resistance and healthspan of C. elegans via AKT signaling pathway.

Yuanyuan Wu, Wei Tang, Yuting Ding, Yanan Zhao, Chenxi Zhou, Yongtao Cheng, Ruoyun Dong, Yang Li, Guoping Zhao, An Xu, Ying Liu.

  The global demographic is witnessing an unprecedented surge in aging, precipitating a dramatic rise in geriatric diseases and related health complications. Although probiotics have been extensively shown to maintain microbiome stability and confer health benefits, their potential role in decelerating the aging process remains largely unexplored. The study identified a beneficial gut microbe from human intestinal tract, Enterococcus faecalis SI-FC-01, which was proved to be biosafe and found to enhance the average lifespan of C. elegans by 33.55%. More interestingly, the E. faecalis SI-FC-01 also enhanced the motor ability, memory and learning ability and anti-oxidative stress ability of C. elegans. Moreover, it exhibited neuroprotective effects in the worm models of neurodegenerative diseases such as Parkinson's disease and Huntington's disease. Through screening various aging-associated mutants of C. elegans, we discovered that E. faecalis SI-FC-01 modulates DAF-16/FOXO signaling via the activation of AKT pathway. This activation subsequently triggers stress resistance and immune-related genes downstream of daf-16, thereby promoting healthspan and neuroprotection. In summary, our research indicates that E. faecalis SI-FC-01 holds significant potential as a dietary supplement for delaying host aging. Furthermore, it provides novel insights for potentially mitigating the progression of age-related neurodegenerative diseases.

Keywords:   Caenorhabditis elegans ; Enterococcus faecalis ; Aging; Healthspan; Neurodegenerative diseases

DOI:  https://doi.org/10.1038/s41598-025-98440-y
Mol Neurobiol. 2025 May 02.

Leaf miRNAs of Withania somnifera Negatively Regulate the Aging-Associated Genes in C. elegans.

Shilpi Yadav, Ravi Kr Gupta, Sailendra Kumar, Anamta Rizvi, Divya Tyagi, Aruna Satish, Digvijay Verma, Akanksha Vishwakarma, Sangeeta Saxena.

  Aging is a physiological process that culminates in cellular senescence, a phenomenon that has significant implications for health and longevity. Plant-based therapeutics, particularly the root of Withania somnifera, have been reported to delay the onset and progression of aging and its associated disorders, including Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders. However, the role of leaf-derived microRNAs (miRNAs) from W. somnifera in the molecular regulation of genes involved in aging remains poorly understood. Caenorhabditis elegans serves as an indispensable model organism for studying aging-associated gene regulation due to its short lifespan, conserved human orthologs, and ease of laboratory cultivation. In this study, we explored the regulatory interactions between miRNAs derived from the leaf tissues of W. somnifera and aging-associated genes, utilizing C. elegans as a model organism. We employed bioinformatics to identify miRNAs that interact with aging-associated genes in C. elegans and found that three specific miRNAs in the leaf tissue of W. somnifera interacted with these genes. To assess the physiological effects of these miRNAs on C. elegans, we conducted biochemical assays, including lifespan, chemotaxis, and stress resistance assays. Additionally, we investigated the differential gene expression of the interacting genes in the presence and absence of W. somnifera leaf miRNA treatment using real-time PCR. The results indicated that the expression levels of the age-1 and sel-12 genes were significantly downregulated, while the apl-1 gene was upregulated following treatment with leaf miRNAs in C. elegans. These findings suggest that miRNAs derived from W. somnifera leaves may play a crucial role in regulating aging-associated gene expression. This is the first study, to our knowledge, that identifies the miRNAs of W. somnifera leaf involved in aging-associated gene regulation, thereby paving the way for future research into the therapeutic potential of plant-derived miRNAs in combating age-related disorders.

Keywords:   C. elegans ; W. somnifera ; Aging; Cross-kingdom regulation; MiRNAs

DOI:  https://doi.org/10.1007/s12035-025-04995-2
World J Gastroenterol. 2025 Apr 21. 31(15): 103773

Delaying liver aging: Analysis of structural and functional alterations.

Yu-Qin Yao, Qiong-Yue Cao, Zheng Li.

  This article is based on a recent bibliometric analysis of research progress on liver aging. The liver is notable for its extraordinary ability to rejuvenate, thereby safeguarding and maintaining the organism's integrity. With advancing age, there is a noteworthy reduction in both the liver's size and blood circulation. Furthermore, the wide range of physiological alterations driven on by aging may foster the development of illnesses. Previous studies indicate that liver aging is linked to impaired lipid metabolism and abnormal gene expression associated with chronic inflammation. Factors such as mitochondrial dysfunction and telomere shortening accumulate, which may result in increased hepatic steatosis, which impacts liver regeneration, metabolism, and other functions. Knowing the structural and functional changes could help elderly adults delay liver aging. Increasing public awareness of anti-aging interventions is essential. Besides the use of dietary supplements, alterations in lifestyle, including changes in dietary habits and physical exercise routines, are the most efficacious means to decelerate the aging process of the liver. This article highlights recent advances in the mechanism research of liver aging and summarizes the promising intervention options to delay liver aging for preventing related diseases.

Keywords:  Caloric restriction; Hepatocytes; Liver aging; Physical exercise; Regeneration; Telomere

DOI:  https://doi.org/10.3748/wjg.v31.i15.103773
Cell Mol Biol Lett. 2025 Apr 30. 30(1): 53

Cdkn1a silencing restores myoblast differentiation by inducing selective apoptosis in senescent cells.

Sujin Kim, Bonsang Gu, Chan-Young So, Keren Esther Kristina Mantik, Seung-Hyun Jung, Sohee Moon, Dong-Ho Park, Hyo-Bum Kwak, Jinkyung Cho, Eun-Jeong Cho, Jae-Seon Lee, Ju-Hee Kang.

   BACKGROUND: Sarcopenia, characterized by a progressive loss of skeletal muscle mass and function, is associated with the accumulation of senescent muscle stem cells, which impair muscle regeneration and contributes to the decline in muscle health. Cdkn1a, which encodes p21, is a well-known marker of cellular senescence. However, it remains unclear whether p21 inhibition eliminates senescent myoblasts and restores the differentiation capacity.
METHODS: We performed transcriptomic analysis to identify genes related to aging-induced sarcopenia using 21 month-old Sprague-Dawley rats. To investigate the specific role of Cdkn1a gene in muscle aging, we used an in vitro model of ceramide-induced senescence in myoblasts, which was verified by the upregulation of p21 and increased senescence-associated beta-galactosidase (SA-β-gal) staining. To inhibit p21, we treated myoblasts with small interfering RNA (siRNA) targeting Cdkn1a. Using fluorescence-activated cell sorting, we separated subpopulations of cells with high or low caspase 3/7 activity. Protein expression related to myogenesis, muscle atrophy, protein synthesis, and apoptosis were quantified by western blotting.
RESULTS: In our transcriptomic analysis, we identified Cdkn1a as an upregulated gene in both the soleus and white gastrocnemius muscles of aged rats, among 36 commonly upregulated genes. The upregulation of Cdkn1a appears to be linked to mitochondrial dysfunction and cellular senescence, underscoring its significance in sarcopenia pathogenesis. C2-ceramide treatment effectively induced senescence, as evidenced by increased p21 expression, enhanced SA-β-gal staining, decreased myogenesis, and increased apoptosis. Knockdown of p21 in ceramide-treated myoblasts significantly reduced SA-β-gal-positive cells, restored cell proliferation, reduced the expression of senescence-associated cytokines (i.e., interleukin (IL)-6 and tumor necrosis factor (TNF)-α), and selectively induced apoptosis in the senescent cell population, demonstrating a senolytic effect. Notably, p21 inhibition also improved differentiation of myoblasts into myotubes, as indicated by increased myosin heavy chain expression and improvements in myotube diameter and fusion index.
CONCLUSIONS: Our data suggest that p21 inhibition selectively eliminates senescent cells while simultaneously enhancing the regenerative capacity of healthy myoblasts, which may combine to improve muscle regeneration and promote myogenesis, ultimately improving muscle health and function in aged individuals.

Keywords:   Cdkn1a ; Myogenesis; Sarcopenia; Senescence; Senolysis; p21

DOI:  https://doi.org/10.1186/s11658-025-00731-9
Biol Res. 2025 May 02. 58(1): 24

Inhibition of CD45-specific phosphatase activity restores the differentiation potential of aged mesenchymal stromal cells: implications in regenerative medicine.

Madhurima Das, Isha Behere, Ganesh Ingavle, Anuradha Vaidya, Vaijayanti Prakash Kale.

   BACKGROUND: Aging affects the reparative potency of mesenchymal stem/stromal cells (MSCs) by diminishing their proliferation and differentiation capability; making them unsuitable for regenerative purposes. Earlier we showed that MSCs acquire the expression of CD45 as a consequence of aging, and this increased expression is associated with downregulated expression of osteogenic markers and upregulated expression of adipogenic and osteoclastogenic markers. However, whether CD45 is actively involved in the aging-mediated deregulated differentiation in the MSCs was not elucidated.
RESULTS: In the present study, we showed that pharmacological inhibition of CD45-specific phosphatase activity in the aged MSCs restores their differentiation potential to young-like. Investigation of the molecular mechanism involved in the process showed that several regulatory kinases like p38, p44/42, Src, and GSK3β are in their dephosphorylated form in the aged MSCs, and importantly, this status gets reversed by the application of a CD45-specific PTP inhibitor. Conversely, pharmacological inhibition of these kinases in young MSCs imposes an aged-like gene expression profile on them. Additionally, we also showed that the secretome of aged MSCs affects the viability and differentiation of primary chondrocytes, and this detrimental effect is reversed by treating aged MSCs with the PTP inhibitor. Our data demonstrate that the aging-mediated expression of CD45 in MSCs alters their differentiation profile by dephosphorylating several kinases and treating the aged MSCs with a CD45 PTP activity inhibitor rejuvenates them.
CONCLUSIONS: CD45 can be used as an aging marker for mesenchymal stem cells. Alteration of CD45 phosphatase activity could have significant implications for the use of MSCs in regenerative medicine.

Keywords:  CD45; Differentiation; Mesenchymal stem/stromal cells; Protein tyrosine phosphatase; Regenerative medicine; Regulatory kinases

DOI:  https://doi.org/10.1186/s40659-025-00603-8
Biomolecules. 2025 Apr 08. pii: 545. [Epub ahead of print]15(4):

Is Senolytic Therapy in Cardiovascular Diseases Ready for Translation to Clinics?

Zhihong Yang, Duilio M Potenza, Xiu-Fen Ming.

  Aging is a predominant risk factor for cardiovascular diseases. There is evidence demonstrating that senescent cells not only play a significant role in organism aging but also contribute to the pathogenesis of cardiovascular diseases in younger ages. Encouraged by recent findings that the elimination of senescent cells by pharmacogenetic tools could slow down and even reverse organism aging in animal models, senolytic drugs have been developed, and the translation of results from basic research to clinical settings has been initiated. Because numerous studies in the literature show beneficial therapeutic effects of targeting senescent cells in cardiomyopathies associated with aging and ischemia/reperfusion and in atherosclerotic vascular disease, senolytic drugs are considered the next generation of therapies for cardiovascular disorders. However, recent studies have reported controversial results or detrimental effects caused by senolytic therapeutic approaches, including worsening of cardiac dysfunction, instability of atherosclerotic plaques, and even an increase in mortality in animal models, which challenges the translation of senolytic therapy into the clinical practice. This brief review article will focus on (1) analyzing and discussing the beneficial and detrimental effects of senolytic therapeutic approaches in cardiovascular diseases and cardiovascular aging and (2) future research directions and questions that are essential to understand the controversies and to translate preclinical results of senolytic therapies into clinical practice.

Keywords:  aging; atherosclerosis; heart; senescent cells; senolytics

DOI:  https://doi.org/10.3390/biom15040545
J Extracell Vesicles. 2025 Apr;14(4): e70065

Plasma Extracellular Vesicle-Derived miR-296-5p is a Maturation-Dependent Rejuvenation Factor that Downregulates Inflammation and Improves Survival after Sepsis.

Lun Cai, Parmita Kar, Yutao Liu, Xiaogang Chu, Ashok Sharma, Tae Jin Lee, Ali Arbab, Raghavan Pillai Raju.

There is a progressive decline in physiological function with age, and aging is associated with increased susceptibility to injury and infection. However, several reports have indicated that the agility of youth is characterized by transferable rejuvenating molecular factors, as was observed previously in heterochronic parabiosis experiments. These experiments demonstrated a rejuvenating effect of young blood in old animals. There have been several efforts to characterize these youthful or maturation-associated factors in the young blood. In this report, we demonstrate the resilience of young mice, at or before puberty, to polymicrobial sepsis and show an age-dependent effect of small extracellular vesicles (EVs) from plasma on the outcome following sepsis. The EVs from the young mice were cytoprotective, anti-inflammatory, and reduced cellular senescence markers. MicroRNA sequencing of the EVs showed an age-associated signature and identified miR-296-5p and miR-541-5p to progressively reduce their levels in the blood plasma with increasing age. We further show that the levels of these miRNAs decline with age in multiple organs. The miRNAs miR-296-5p and miR-541-5p showed a reparatory effect in an in vitro wound healing model and the miR-296-5p, when given intraperitoneally, reduced mortality in the mouse model of sepsis. In summary, our studies demonstrate that EVs from very young mice have a reparative effect on sepsis, and the reparative factors are likely maturation-dependent. Our observation that miR-296-5p and miR-541-5p are plasma EV constituents that significantly reduce with age and can reduce inflammation suggests a therapeutic potential for these miRNAs in inflammation and age-associated diseases.

DOI: https://doi.org/10.1002/jev2.70065
Redox Biol. 2025 Apr 18. pii: S2213-2317(25)00153-3. [Epub ahead of print]83 103640

Taurine ameliorates cellular senescence associated with an increased hydrogen sulfide and a decreased hepatokine, IGFBP-1, in CCl4-induced hepatotoxicity in mice.

Akihiro Tsuboi, Hamida Khanom, Riki Kawabata, Takanori Matsui, Shigeru Murakami, Takashi Ito.

  This study investigated the protective effects of taurine against cellular senescence and hepatokine secretion in a mouse model of carbon tetrachloride (CCl4)-induced chronic liver injury. Oral taurine administration by tap water containing 3 % taurine significantly attenuated liver damage, as evidenced by reduced serum AST, ALT level and hepatic lipid peroxidation. Importantly, hepatic taurine level is reduced in CCl4-induced injury model, while taurine administration recovered it. Moreover, taurine administration decreased the numbers of p21-positive senescent cells in liver tissue of CCl4-treated mice. Taurine increases hydrogen sulfide (H2S) in liver of normal mice, suggesting anti-oxidative role through H2S production by taurine. Furthermore, inhibition of CTH, which is an enzyme responsible for H2S production from cysteine, by propagylglycine attenuated malondialdehyde-lowering effect of taurine in liver of CCl4-treated mice. Moreover, we found taurine treatment lowers insulin-like growth factor binding protein-1 (IGFBP-1) in liver of normal mice. Importantly, while chronic CCl4 injection caused an induction of IGFBP-1, taurine administration blocked it. These findings suggest that taurine exerts its protective effects by attenuating cellular senescence, which is associated with enhancing H2S production and inhibiting IGFBP-1 expression. This study highlights the potential of taurine as a therapeutic strategy for mitigating chronic liver injury by producing H2S and targeting IGFBP1.

Keywords:  Hepatokines; Hydrogen sulfide; IGFBP-1; Liver injury; Senescence; Taurine

DOI:  https://doi.org/10.1016/j.redox.2025.103640
J Am Chem Soc. 2025 May 01.

Click Chemistry-Assisted Rejuvenation of Aging T Cells Sensitizes Aged Mice to Tumor Immunotherapy.

Xue-Feng Bai, Jun-Chi Ma, Cheng Zhang, Zhu Chen, Jinlian He, Si-Xue Cheng, Xian-Zheng Zhang.

Enormous resources have been devoted to address the suboptimal response of tumor patients to immunotherapy. However, a crucial yet often overlooked factor in these effects is the strong correlation between the occurrence and development of tumors and the immune dysfunction associated with aging. Our study aims to rejuvenate aging T cells within tumor-draining lymph nodes (TdLNs) by using targeted delivery of rapamycin, a macrolide capable of mitigating aging-related decline in immune function, thereby enhancing the antitumor efficacy of immunotherapy in aged mice. The targeted delivery system relies on a bioorthogonal reaction that harnesses the click chemistry between the azide (N3) groups artificially introduced onto TdLNs and the dibenzocyclooctyne (DBCO) groups attached to the rapamycin-loaded micelles administered intradermally. Experimental data demonstrate that this approach has effectively restored the functionality of impaired CD8+ T cells in aged mice, thereby enhancing the antitumor response to immune checkpoint blockade (ICB) therapy to levels comparable to those in young mice. This study presents a promising strategy to combat the resistance to immunotherapeutic approaches commonly encountered among elderly tumor patients.

DOI: https://doi.org/10.1021/jacs.5c05312
Curr Opin Genet Dev. 2025 Apr 30. pii: S0959-437X(25)00043-7. [Epub ahead of print]93 102351

Unlocking regeneration: how partial reprogramming resembles tissue healing.

Melissa T Adams, Heinrich Jasper, Lluc Mosteiro.

Partial reprogramming achieved by the transient expression of the transcription factors (TFs) Oct4, Sox2, Klf4 and C-Myc (abbreviated OSKM) can erase aging and damage features in cells, leading to increased healthspan, lifespan and tissue regeneration. Recent reports suggest that the mechanisms of partial reprogramming may share some similarities with natural dedifferentiation and regeneration. Both processes appear to involve the transient repression of somatic identity through the sequestration of somatic identity TFs to noncanonical sites, which are opened by the high expression of pioneer TFs, leading to transient dedifferentiation into a fetal-like state. Here, we review the reported benefits of partial reprogramming on tissue regeneration and propose a common mechanism of epigenetic remodeling with natural regeneration after tissue injury.

DOI: https://doi.org/10.1016/j.gde.2025.102351
Drug Des Devel Ther. 2025 ;19 3059-3076

Gui-Pi-Tang Defers Skeletal Muscle and Cardiac Muscle Aging by Promoting Mitochondrial Remodeling.

Changjiu Cai, Manying Wang, Dan Yang, Chenxu Jing, Yingna Li, Hanying Xu, Fangbing Liu, Daqing Zhao.

   Purpose: To determine whether Gui-Pi-Tang (GPT) has protective effects on skeletal muscle and cardiac muscle in aged mice.
Methods: This study used C57BL6/J mice to establish an in vivo natural aging model, while D-galactose (D-gal)-injured C2C12 and H9c2 cells were employed to create in vitro aging cell models. Hematoxylin and eosin (H&E) staining was used to assess the effect of GPT on skeletal and cardiac muscle in aged mice. Protection against age-induced cellular damage by GPT was assessed in C2C12 and H9c2 cells using β-galactosidase staining. Mitochondrial morphology, structure, and function were analyzed using transmission electron microscopy, Seahorse assays, and ATP content measurements. Potential mechanisms by which GPT regulates mitochondrial homeostasis were examined using Western blot analysis.
Results: GPT treatment significantly improved the alignment of skeletal muscle fibers, reduced gaps, and increased the cross-sectional area (CSA) of skeletal muscle in aged mice. It also reduced the CSA of cardiac muscle fibers, alleviating cardiomyocyte hypertrophy. Mitochondrial morphology was restored, and GPT reduced D-gal-induced β-galactosidase elevation. Furthermore, GPT protected mitochondrial morphological and structural integrity in the skeletal and cardiac muscles of aged mice and improved mitochondrial respiratory function and ATP levels in D-gal-injured C2C12 and H9c2 cells. GPT treatment increased the levels of mitochondrion-associated proteins PGC-1α, PPARγ, Nrf1, and OPA1 in the skeletal and cardiac muscle of aged mice. Moreover, GPT modulated Drp1 expression, with increases in aged skeletal muscle and decreases in aged cardiac muscle.
Conclusion: These findings suggest that GPT helps maintain mitochondrial homeostasis by regulating mitochondrial remodeling, thereby alleviating skeletal and cardiac muscle damage in aged mice.

Keywords:  Gui-Pi-Tang; mitochondrial homeostasis; myocardium; senescence; skeletal muscle

DOI:  https://doi.org/10.2147/DDDT.S509046
Free Radic Biol Med. 2025 Apr 23. pii: S0891-5849(25)00242-4. [Epub ahead of print]

Polydatin reactivates mitochondrial bioenergetics and mitophagy while preventing premature senescence by modulating microRNA-155 and its direct targets in human fibroblasts with trisomy 21.

Daniela Valenti, Daniela Isabel Abbrescia, Flaviana Marzano, Giampietro Ravagnan, Apollonia Tullo, Rosa Anna Vacca.

  Mitochondrial dysfunction and redox dyshomeostasis are considered crucial factors causally linked to the pathogenesis of Down syndrome (DS), a human genetic anomaly currently lacking a cure, associated with neurodevelopmental deficits in children and early onset symptoms of aging in adults. Several natural plant-derived polyphenolic compounds, known for their neurostimulator, antioxidant and anti-inflammatory activities, have been proposed as dietary supplements to manage DS-linked phenotypic alterations. However, the poor bioavailability and rapid metabolism of these compounds have limited conclusive evidence regarding their clinical efficacy in individuals with DS. Polydatin (PLD), a natural polyphenolic glucoside precursor of resveratrol derived from Polygonum cuspidatum, is instead highly bioavailable and resistant to enzymatic oxidation. PLD supplementation has shown many therapeutic efficacies in several human diseases without side effects. In this study, we used fetal trisomy 21 human skin fibroblasts (DS-HSFs) to investigate, from a mechanistic point of view, whether PLD supplementation could prevent or counteract critical cellular alterations linked to both neurodevelopmental deficits and early aging in DS. Our findings demonstrate that PLD reactivates mitochondrial bioenergetics, reduces oxygen radical overproduction and prevents oxidative stress (OS)-induced cellular senescence and DNA damage in DS-HSF. Notably, we identified a novel mechanism of PLD action involving the chromosome-21-encoded microRNA-155 (miR-155) and its direct target genes casitas B-lineage lymphoma (CBL), BAG Cochaperone 5 (BAG5) and mitochondrial transcription factor A (TFAM). These proteins play pivotal roles in regulating mitochondrial bioenergetics, biogenesis and mitophagy. Given that the deregulation of miR-155/CBL axis is also implicated in acute leukemias, which frequently occur in children with DS, PLD emerges as a promising candidate for translational application. Its ability to enhance mitochondrial bioenergetics and address critical DS-associated phenotypic alterations highlights its therapeutic potential.

Keywords:  BAG Cochaperone 5; Down syndrome; Polydatin supplementation; aging; casitas B-lineage lymphoma; leukemia; miR-155; mitochondrial bioenergetics; mitophagy; oxidative stress; senescence

DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.04.032
Ann Med. 2025 Dec;57(1): 2496409

Multidomain intervention for delaying aging in community-dwelling older adults (MIDA): study design and protocol.

Siyang Lin, Fang Wang, Min Huang, Jingyi Chen, Xinye Jiang, Qiaowei Li, Yin Yuan, Feng Huang, Pengli Zhu.

   BACKGROUND: The exploration of interventions to delay aging is an emerging topic that promotes healthy aging. The multidomain intervention has the potential to be applied in the field of aging because it concentrates on the functional ability of older adults. There is currently no literature reporting on a multidomain intervention involving cognition, exercise and nutrition for delaying aging.
METHODS: The Multidomain Intervention for Delaying Aging in Community-dwelling Older Adults (MIDA) is a Zelen-design randomized controlled trial with a 6-month intervention duration. The multidomain intervention comprises cognitive training, exercise training, and nutritional guidance, delivered through both group sessions and individual family interventions. A total of 248 participants aged 60 to 85 years will be randomized to the intervention group or control group and followed up for 12 months. The primary outcome is the change in epigenetic age acceleration and pace of aging following the multidomain intervention. The secondary outcomes are the changes in frailty score and intrinsic capacity Z-score. Other outcomes include physical functions, body composition, aging biomarkers, inflammatory markers, haematology and biochemistry parameters, and lifestyle factors.
CONCLUSIONS: This study will explore the effects of the multidomain intervention on delaying aging in community-dwelling older adults. We aim to introduce a new approach to delaying aging and offer a practical multidomain intervention strategy for healthcare institutions.

Keywords:  DNA methylation age; Multidomain intervention; biological age; frailty; intrinsic capacity

DOI:  https://doi.org/10.1080/07853890.2025.2496409
Polymers (Basel). 2025 Mar 18. pii: 798. [Epub ahead of print]17(6):

Current Approaches in Cosmeceuticals: Peptides, Biotics and Marine Biopolymers.

Ulya Badilli, Ozge Inal.

  Today's consumer perception and expectations of personal care have gone beyond merely cleansing, moisturizing, and makeup products, focusing more on the reduction or elimination of signs of aging. Cosmeceuticals, developed to create a more youthful appearance, commonly contain substances with therapeutic and physiological effects. The development of cosmeceutical products containing peptides, biotic ingredients, and marine-based compounds has become a highly popular strategy to enhance anti-aging effects and better address consumer demands. Peptides are frequently used in anti-aging products due to their effects on enhancing fibroblast proliferation and collagen synthesis, contributing to the skin's barrier function, and reducing skin pigmentation. Meanwhile, biotic components are extensively evaluated for their potential to improve barrier function by maintaining the balance of the skin microflora. On the other hand, the increasing interest of cosmetic consumers in natural and eco-friendly products, along with the rich biodiversity in the oceans and seas, has made marine-derived substances highly significant for the cosmetic industry. Marine polysaccharides are particularly valuable as biopolymers, offering useful properties for gel formation in cosmetic formulations. This review discusses scientific studies and commercially available products using peptides, biotic and marine-based compounds in cosmetic formulations, their cosmetic and cosmeceutical benefits, and the challenges in the formulation design of these products.

Keywords:  bioactive agents; biopolymers; biotics; cosmetic product; marine ingredients; natural compounds; peptides

DOI:  https://doi.org/10.3390/polym17060798
Facial Plast Surg. 2025 Apr 30.

Evaluation and Treatment Planning to Maximize Perioral, Submental, and Neck Aesthetics.

Cheng Ma, Aniruddha Parikh, Jessyka G Lighthall.

a. Aims and Backgrounds Aesthetic rejuvenation of the perioral, submental, and neck regions is a complex topic with multiple different treatment approaches. Aging changes in the skin, muscles, fat and soft tissue, and bones are driven by multiple internal and external factors. To obtain the best cosmetic outcome, a deep understanding of the perioral, submental, and neck region and proper patient evaluation are necessary. Here, we discuss the process of evaluating patients and planning treatment for perioral, submental, and neck rejuvenation. b. Patient Selection Patients presenting for evaluation of perioral, submental, and neck aging may have multiple aesthetic complaints. The approach to evaluating patients should be comprehensive and consistent. This involves careful history taking and consideration of medical co-morbidities, thorough evaluation of the skin, tone, dynamic movement, and soft-tissue distribution of each subunit, and individualized pre-treatment counseling to discuss risks and set expectations. c. Techniques An individualized plan may consist of either non-surgical, surgical, or a combination of approaches. Non-surgical approaches excel at addressing aging skin, volume deficits, and overactivation of facial musculature. Surgical approaches address more severe manifestations of skin aging, uneven volume distribution, loss of contour in the jaw and neck, and bony deformities.

DOI: https://doi.org/10.1055/a-2597-6850
J Cosmet Dermatol. 2025 May;24(5): e70214

Evaluating the Efficacy of Acupotomy Subcision and Hyaluronic Acid Injections for Neck Wrinkles: A Randomized Trial.

Taolue Ni, Fang Ren, Tianqi Zhang, Dong Hua, Gang Chen, Hao Chen.

   BACKGROUND: Horizontal neck wrinkles are a prevalent sign of aging, with emerging research highlighting the effectiveness of treatments such as acupotomy subcision (AS) and hyaluronic acid (HA) injections in rejuvenating aged skin.
AIMS: This study aims to evaluate and compare the efficacy of three distinct treatment modalities for neck wrinkles: AS, HA injections, and a combination of both. The primary objective is to determine which treatment approach offers the most effective and satisfactory outcomes in terms of wrinkle reduction and skin rejuvenation.
METHODS: In this randomized clinical trial, 30 female participants with neck Allergan Transverse Neck Lines Scale (ATNLS) scores ranging from 3 to 4 were randomly allocated into three treatment groups: AS, HA, and AS+HA. Each participant received treatment once a month for 3 months, followed by clinical assessments at 1 month and 6 months posttreatment. The assessments included ATNLS scores, Global Aesthetic Improvement Scores (GAIS), and analysis of skin elasticity and collagen levels.
RESULTS: All treatment groups demonstrated improvements in ATNLS scores and GAIS after the final treatment. Notably, the AS+HA group showed a significantly higher number of participants reporting beneficial results at the 6-month follow-up. This group also exhibited a statistically significant increase in skin elasticity and collagen levels compared to the other groups.
CONCLUSION: The combined approach of HA and acupotomy subcision is effective in treating horizontal neck wrinkles, leading to significant improvements in skin elasticity and collagen levels. This study suggests that the synergistic effect of AS and HA may enhance the overall efficacy of treatments for reducing neck wrinkles, providing a promising option for patients seeking noninvasive neck rejuvenation.

Keywords:  acupotomy subcision; hyaluronic acid injections; neck wrinkles; needle knife scripping

DOI:  https://doi.org/10.1111/jocd.70214
Pharmaceuticals (Basel). 2025 Mar 28. pii: 483. [Epub ahead of print]18(4):

Inhibition of GSK-3β Restores Differentiation Potential of Late-Passage Mesenchymal Stem Cells.

Kavitha Govarthanan, Raja Sundari Meenakshi Sundaram, Arthi Sunil Richard, Siva Chander Chabathula, Secunda Rupert, Jeswanth Sathyanesan, Rama Shanker Verma, Naveen Jeyaraman, Madhan Jeyaraman, Ramya Lakshmi Rajendran, Prakash Gangadaran, Byeong-Cheol Ahn.

  Background/Objectives: Mesenchymal stem cells (MSCs) are regarded as a promising cell type with significant therapeutic benefits owing to their ease of isolation, maintenance, and characterisation. However, repeated passages during cultural maintenance frequently result in cellular senescence, limiting their utility in regenerative medicine. Methods: We investigated the differentiation capability between early- (P3) and late-passage MSCs (>P15) and tested the potential of Wnt agonist 99021 to reverse MSCs using standard cell culture protocols that define minimal criteria for MSCs, primarily tri-lineage differentiation assays, biochemical staining gene expression analysis, and senescence assays. Results: We initially noticed distinct signs of morphological aging between early- (P3) and late-passage MSCs (>P15) and further examined the differentiation capability between early- (P3) and late-passage MSCs (>P15). We found a diminished differentiation potential in late-passage MSCs. Our senescence assay also revealed >P15 cells were able to absorb the senescence dye, indicating that >P15 MSCs underwent senescence. We further demonstrated that CHIR 99021 reversed the differentiation inhibitory potential-mediated impasse of late-passage MSCs by employing tri-lineage specific differentiation assays, biochemical labelling, and gene expression analysis. Senescence assays after CHIR 99021 treatment also revealed no senescence dye uptake at all. Conclusions: Our findings demonstrated that CHIR 99021 Wnt agonist maybe aids in the reversal of MSC aging-related differentiation inhibition glitches and offers a proven demonstrated protocol for rejuvenating late-passage MSCs. Thus, CHIR99021 treatment inherently reverts the tri-lineage potency in late-passage MSCs, and this method could be further employed to ensure a plentiful MSC source for clinical purposes.

Keywords:  CHIR 99021; MSCs; differentiation; rejuvenation; senescence; tri-lineage

DOI:  https://doi.org/10.3390/ph18040483
Science. 2025 May;388(6746): eadp2959

Stem cells as role models for reprogramming and repair.

Magdalena Götz, Maria-Elena Torres-Padilla.

Stem cells are a promising source for cellular therapies across many diseases and tissues. Their inherent ability to differentiate into other cell types has been the focus of investigation over decades. This ability is currently being exploited for therapies using strategies to repair or replace damaged tissues and cells or to alleviate immune rejection. Exploring stem cell function has enabled direct reprogramming approaches, for example, through the production of induced pluripotent stem cells and the generation of tissue-specific stem cells. Understanding stem cell function has emerged as an important strategy for repopulating stem cell pools or generating differentiated cells for therapy. Here, we review general principles of mammalian stem cell biology and cellular reprogramming approaches and their use for current and future therapeutic purposes.

DOI: https://doi.org/10.1126/science.adp2959
Nutrients. 2025 Mar 10. pii: 969. [Epub ahead of print]17(6):

Exercise Mimetics in Aging: Suggestions from a Systematic Review.

Emiliana Giacomello, Claudio Nicoletti, Marta Canato, Luana Toniolo.

  Background/Objectives: Growth in the aging world population is accompanied by an increase in comorbidities, profoundly impacting the quality of life of older people. This development has motivated a large effort to investigate the mechanisms underlying aging and the search for countermeasures. The most investigated strategies envisage the control of diet and physical exercise, which exploit both common and distinct mechanisms to promote health. Since the application of nutritional and exercise protocols to aged persons introduces several issues due to their disabled state, some strategies have been developed. The nutritional approach exploits a wide range of compounds, including calorie restriction mimetics, supplements, antioxidants, and others. In the context of exercise, in recent years, molecules able to provide similar effects to exercise, the so-called exercise mimetics, have been developed. Methods: To have a better perspective on exercise mimetics and their connection with nutrition, we performed a systematic search of the PubMed and Scopus databases using the term "exercise mimetics". Results: In total, 97 research articles were selected and discussed. The present review provides evidence of the presence of multiple exercise-mimetic compounds and physical strategies that can target metabolic pathways, oxidative stress defense mechanisms, or myokine modulation. Conclusions: Interestingly, this review highlights that an important number of exercise mimetics are represented by products of natural origin and supplements assimilable with diet. This evidence provides a further link between exercise and nutrition and confers a central role on nutrition in the context of exercise mimetics.

Keywords:  aging; exercise; exercise mimetics; health span; lifespan; metabolism; myokines; natural compounds; nutrient sensing pathway

DOI:  https://doi.org/10.3390/nu17060969
Aging Cell. 2025 Apr 30. e70075

Identifying Age-Modulating Compounds Using a Novel Computational Framework for Evaluating Transcriptional Age.

Chao Zhang, Nathalie Saurat, Daniela Cornacchia, Sun Young Chung, Trisha Sikder, Adrianne Nemchik, Andrew Minotti, Lorenz Studer, Doron Betel.

  The differentiation of human pluripotent stem cells (hPSCs) provides access to a wide range of cell types and tissues. However, hPSC-derived lineages typically represent a fetal stage of development, and methods to expedite the transition to an aged identity to improve modeling of late-onset disease are limited. In this study, we introduce RNAge, a transcriptome-based computational platform designed to enable the evaluation of an induced aging or a rejuvenated state. We validated this approach across independent datasets spanning different tissues and species, and show that it can be used to evaluate the effectiveness of existing age-retaining or age-modulating interventions. We also used RNAge to perform an in silico compound screen using the LINCS L1000 dataset. This approach led to the identification and experimental confirmation of several novel compounds capable of inducing aging or rejuvenation in primary fibroblasts or hPSC-derived neurons. Additionally, we observed that applying this novel induced aging strategy to an hPSC model of Alzheimer's disease (AD) accelerated neurodegeneration in a genotype-specific manner. Our study offers a robust method for quantifying age-related manipulations and unveils compounds that significantly broaden the toolkit for age-modifying strategies in hPSC-derived lineages.

Keywords:  Alzheimer's disease; age score; aging; cortical neurons; disease modeling; human pluripotent stem cells; transcriptional age

DOI:  https://doi.org/10.1111/acel.70075
Int J Biol Macromol. 2025 Apr 29. pii: S0141-8130(25)04213-8. [Epub ahead of print] 143661

Alhagi camelorum seed polysaccharide alleviates methylglyoxal-induced skin damage via antioxidant and anti-inflammatory actions.

Quanxing Chen, Mingjie Li, Zhiwei Li, Manxue Mei, Ying Lin, Peng Shu, Wei Zhu.

  Alhagi camelorum (AC) is an herbal medicine known for its anti-inflammatory and antioxidant properties. However, the mechanism by which AC affects skin aging remains unclear. In this study, a polysaccharide with antioxidant activity was extracted from AC seeds (ACSP). The structure of ACSP was characterized by molecular weight determination, Fourier transform infrared spectroscopy, monosaccharide composition analysis, scanning electron microscopy, and physicochemical analysis. The molecular weight of ACSP was 736,831 Da. ACSP, devoid of a triple-helical conformation, comprised mannose, rhamnose, galacturonic acid, glucose, galactose, and arabinose at a molar ratio of 39.65:0.85:0.59:11.57:40.25:6.60. The anti-skin-aging activity and potential mechanisms of action of ACSP were investigated in vitro. We observed that ACSP delayed the onset of senescence, promoted cell migration, decreased the expression of DNA damage markers and the production of reactive oxygen species, and increased the mitochondrial membrane potential in damaged cells. ACSP also significantly reduced the expression of the inflammatory mediators interleukin (IL)-6, IL-1β, and tumor necrosis factor-α in HaCaT cells. In addition, ACSP attenuated the expression of proteins within the IL-17 signaling pathway and suppressed the phosphorylation of JAK2/STAT3/NF-κB proteins, thereby exerting a senescence-delaying effect on MGO-induced HaCaT cells. In conclusion, we elucidated the potential of ACSP in delaying skin aging and offer a novel plant-derived adjuvant to delay aging.

Keywords:  Alhagi camelorum; Anti-inflammatory; Antioxidant; IL-17 signaling pathway; Polysaccharide; Skin aging

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.143661
Cureus. 2025 Mar;17(3): e81244

Investigating the Effects of a Manuka Honey, Royal Jelly, and Bee Venom-Derived Face Serum on Skin Health and Signs of Aging.

Ellen O'Gorman, Swathi Varanasi, Scott Bukoski, Susanne Mitschke, Scott Conger.

   OBJECTIVE: The purpose of this study was to investigate the efficacy of a commercially available manuka honey-based face serum that includes royal jelly and bee venom on various ingredients frequently associated with skin health benefits over an eight-week period.
MATERIALS AND METHODS: Forty female participants aged 40-55 with self-reported skin health concerns were recruited. Participants used the serum twice daily and completed questionnaires during Weeks 2, 4, and 8. Photos of the face were analyzed for dermatological skin grading and Optic Elite facial analysis at Week 8.
RESULTS: There were significant improvements in fine lines, wrinkles, dark spots, hyperpigmentation, dryness, and overall skin health beginning at Week 2, with sustained enhancements observed until Week 8. Dermatologist skin grading results were mixed, with 20 (60.6%) of participants demonstrating improvements in skin brightness, but lower percentages of participants showed improvement in overall skin health, fine lines/wrinkles, roughness, pigmentation, and redness/erythema. Optic Elite analysis showed improvements in several skin health scores, providing further evidence for the serum's effects on skin health. Participants self-reported high satisfaction with the effectiveness of the serum.
CONCLUSIONS: These findings suggest that the face serum may be an effective skincare product for improving skin health and mitigating signs of aging.

Keywords:  dark spots; dry skin; fine lines; skincare; wrinkles

DOI:  https://doi.org/10.7759/cureus.81244