bims-caglex 2025-05-18 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2025–05–18
twenty-one papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

Systematic transcriptomics analysis of calorie restriction and rapamycin unveils their synergistic interaction in prolonging cellular lifespan.
Extracellular vesicle as therapeutic agents in anti-aging: Mechanistic insights and future potential.
Decoding Aging through iPSC Reprogramming: Advances and Challenges.
SGLT2 inhibitors as a novel senotherapeutic approach.
The interplay of cellular senescence and reprogramming shapes the biological landscape of aging and cancer revealing novel therapeutic avenues.
In vitro senescence and senolytic functional assays.
Age-related declines in niche self-renewal factors controls testis aging and spermatogonial stem cell competition through Hairless, Imp, and Chinmo.
CircAge: A Comprehensive Resource for Aging-associated Circular RNAs Across Species and Tissues.
Lanatoside C, a Novel Senolytic, Ameliorates Atherosclerosis in Mice.
hTERT Increases TRF2 to Induce Telomere Compaction and Extend Cell Replicative Lifespan.
Ythdf2 Ablation Protects Aged Retina From RGC Dendrite Shrinking and Visual Decline.
Telomeres and Telomerase: Targets for Chemoprevention of Hepatocellular Carcinoma With Bioactive Food Compounds.
PseudoCell: A Multivalued Logical Regulatory Network to Investigate Premature Senescence Dynamics and Heterogeneity.
Body Fluid-Derived Stem Cells: Powering Innovative, Less-Invasive Cell Therapies.
SuoquanYishen formula improves renal cellular senescence by inhibiting YTHDF1-Rubicon axis to promote autophagy in diabetic kidney disease.
Exosomes derived from human umbilical cord mesenchymal stem cells attenuate senescence of peritoneal mesothelial cells by inhibiting oxidative stress.
Lysosomes as Dynamic Regulators of Metabolic Signaling and Organ Physiology in Aging: From Mechanism to Therapy.
Testicular aging: mechanism, management and future therapy.
The Redox Activity of Protein Disulphide Isomerase Functions in Non-Homologous End-Joining Repair to Prevent DNA Damage.
[Network pharmacology and animal experiments reveal molecular mechanisms of Cordyceps sinensis in ameliorating heart aging and injury in mice by regulating Nrf2/HO-1/NF-κB pathway].
Progress, Applications and Prospects of CRISPR-Based Genome Editing Technology in Gene Therapy for Cancer and Sickle Cell Disease.

Commun Biol. 2025 May 14. 8(1): 753

Systematic transcriptomics analysis of calorie restriction and rapamycin unveils their synergistic interaction in prolonging cellular lifespan.

Yizhong Zhang, Arshia Naaz, Trishia Yi Ning Cheng, Jovian Jing Lin, Mingtong Gao, Rajkumar Dorajoo, Mohammad Alfatah.

Aging is a multifaceted biological process marked by the decline in both mitotic and postmitotic cellular function, often central to the development of age-related diseases. In the pursuit of slowing or even reversing the aging process, a prominent strategy of significant interest is calorie restriction (CR), also known as dietary restriction, and the potential influence of a drug called rapamycin (RM). Both CR and RM have demonstrated the capacity to extend healthspan and lifespan across a diverse array of species, including yeast, worms, flies, and mice. Nevertheless, their individual and combined effects on mitotic and postmitotic cells, as well as their comparative analysis, remain areas that demand a thorough investigation. In this study, we employ RNA-sequencing methodologies to comprehensively analyze the impact of CR, RM, and their combination (CR + RM) on gene expression in yeast cells. Our analysis uncovers distinctive, overlapping, and even contrasting patterns of gene regulation, illuminating the unique and shared effects of CR and RM. Furthermore, the transcriptional synergistic interaction of CR + RM is validated in extending the lifespan of both yeast and human cells.

DOI: https://doi.org/10.1038/s42003-025-08178-6
J Control Release. 2025 May 08. pii: S0168-3659(25)00416-X. [Epub ahead of print]383 113796

Extracellular vesicle as therapeutic agents in anti-aging: Mechanistic insights and future potential.

Hyejoo Yoon, Junyeong Jo, Hyesun Hyun, Gyuwon Lee, Seoyoung Ma, Jungho Sohn, Dong Kyung Sung, Chae Young Han, Minkyung Kim, Duhyeong Hwang, Hyunji Lee, Yuseon Shin, Kyung Taek Oh, Chaemin Lim.

  Aging is a multifaceted biological process marked by a gradual decline in physiological functions, driven by cellular senescence, oxidative stress, chronic inflammation, and stem cell exhaustion. Extracellular vesicles (EVs), naturally occurring nanoscale vesicles secreted by various cell types, have gained attention as potential therapeutic agents due to their ability to mediate intercellular communication by delivering bioactive molecules, including proteins, lipids, and RNAs. This review provides a comprehensive overview of EV biogenesis, cargo composition, and their mechanistic roles in counteracting aging processes. EVs from diverse sources-such as mesenchymal stem cells, embryonic stem cells, dermal fibroblasts, and colostrum-exhibit regenerative properties by modulating immune responses, enhancing tissue repair, and promoting extracellular matrix homeostasis. Recent preclinical and clinical studies further highlight their potential in addressing age-related diseases and skin rejuvenation. However, significant challenges remain, including standardization of EV production, large-scale manufacturing, safety profiling, and regulatory approval. By leveraging advancements in EV engineering, targeted delivery systems, and combination strategies with existing anti-aging interventions, EV-based therapies hold promise as next-generation approaches in regenerative medicine and longevity enhancement.

Keywords:  Anti-aging therapy; Anti-inflammation; Cellular senescence; Regenerative medicine; Stem cell-derived EV

DOI:  https://doi.org/10.1016/j.jconrel.2025.113796
Aging Dis. 2025 May 07.

Decoding Aging through iPSC Reprogramming: Advances and Challenges.

Rui-Lin Li, Yun-Zeng Zou, Sheng Kang.

Aging is characterized by cellular senescence and increased susceptibility to age-related diseases. Induced pluripotent stem cell (iPSC) technology demonstrates the potential to reverse aging hallmarks, including telomere attrition, mitochondrial dysfunction, and oxidative stress. Reprogramming somatic cells using factors such as Oct4, Sox2, Klf4, and c-Myc (OSKM) restores pluripotency and reverses aging markers. Partial reprogramming, involving transient OSKM expression, rejuvenates cells by resetting epigenetic clocks, reducing senescence-associated secretory phenotypes (SASPs), and improving mitochondrial function, as evidenced by lifespan extension in progeroid mouse models. These advancements facilitate disease modeling and autologous therapies for neurodegeneration, etc. Critical challenges, including tumorigenicity risks associated with oncogenic reprogramming factors, have been mitigated through non-integrative delivery systems (e.g., mRNA, small molecules) and suicide genes. Persistent epigenetic memory and incomplete reprogramming impede iPSC differentiation, but CRISPR-based tools (e.g., dCas9-DNMT3A, CRISPRoff) allow precise epigenetic editing to erase residual somatic signatures. Variability in iPSC quality, influenced by cell source and culture conditions, necessitates standardized protocols and CRISPR-enhanced quality control. Ethical considerations, such as informed consent and genetic discrimination, highlight the need for governance frameworks that align innovation with societal values. Subsequent priorities include optimizing reprogramming efficiency, validating safety in preclinical models, and translating findings into therapies for age-related disorders. In conclusion, iPSC and CRISPR technologies collectively present transformative strategies to delay aging and restore cellular vitality, paving the way for rejuvenation therapies. Future studies should focus on improving the reprogramming efficiency, minimizing the risk of tumorigenicity, and exploring the optimized CRISPR-based epigenetic editing technique.

DOI: https://doi.org/10.14336/AD.2025.0438
NPJ Aging. 2025 May 10. 11(1): 35

SGLT2 inhibitors as a novel senotherapeutic approach.

Zeynep Elif Yesilyurt-Dirican, Ce Qi, Yi-Chian Wang, Annika Simm, Laura Deelen, Alia Hafiz Abbas Gasim, Fiona Lewis-McDougall, Georgina M Ellison-Hughes.

Cellular senescence is the permanent cessation of cell proliferation and growth. Senescent cells accumulating in tissues and organs with aging contribute to many chronic diseases, mainly through the secretion of a pro-inflammatory senescence-associated secretory phenotype (SASP). Senotherapeutic (senolytic or senomorphic) strategies targeting senescent cells or/and their SASP are being developed to prolong healthy lifespan and treat age-related pathologies. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of anti-diabetic drugs that promote the renal excretion of glucose, resulting in lower blood glucose levels. Beyond their glucose-lowering effects, SGLT2 inhibitors have demonstrated protective effects against cardiovascular and renal events. Moreover, SGLT2 inhibitors have recently been associated with the inhibition of cell senescence, making them a promising therapeutic approach for targeting senescence and aging. This review examines the latest research on the senotherapeutic potential of SGLT2 inhibitors.

DOI: https://doi.org/10.1038/s41514-025-00227-y
Front Cell Dev Biol. 2025 ;13 1593096

The interplay of cellular senescence and reprogramming shapes the biological landscape of aging and cancer revealing novel therapeutic avenues.

Fuan Ding, Ying Yu, Jiangqi Zhao, Shibo Wei, Yan Zhang, Jung Ho Han, Zhuo Li, Hong-Bo Jiang, Dongryeol Ryu, Minkyoung Cho, Sung-Jin Bae, Wonyoung Park, Ki-Tae Ha, Bo Gao.

  Cellular senescence and cellular reprogramming represent two fundamentally intertwined processes that profoundly influence aging and cancer. This paper explores how the permanent cell-cycle arrest of senescent cells and the identity-resetting capacity of reprogramming jointly shape biological outcomes in later life and tumor development. We synthesize recent findings to show that senescent cells, while halting the proliferation of damaged cells, can paradoxically promote tissue dysfunction and malignancy via their secretory phenotype. Conversely, induced reprogramming of somatic cells-exemplified by Yamanaka factors-resets cellular age and epigenetic marks, offering a potential to rejuvenate aged cells. Key findings highlight shared mechanisms (e.g., DNA damage responses and epigenetic remodeling) and bidirectional crosstalk between these processes: senescence signals can facilitate neighboring cell plasticity, whereas reprogramming attempts can trigger intrinsic senescence programs as a barrier. In aging tissues, transient (partial) reprogramming has been shown to erase senescence markers and restore cell function without inducing tumorigenesis, underlining a novel strategy to combat age-related degeneration. In cancer, we discuss how therapy-induced senescence of tumor cells may induce stem-cell-like traits in some cells and drive relapse, revealing a delicate balance between tumor suppression and tumor promotion. Understanding the interplay between senescence and reprogramming is crucial for developing innovative therapies. By targeting the senescence-reprogramming axis-for instance, via senolytic drugs, SASP inhibitors, or safe reprogramming techniques-there is significant therapeutic potential to ameliorate aging-related diseases and improve cancer treatment. Our findings underscore that carefully modulating cellular senescence and rejuvenation processes could pave the way for novel regenerative and anti-cancer strategies.

Keywords:  aging; cancer; cellular senescence; reprogramming; tumor progression

DOI:  https://doi.org/10.3389/fcell.2025.1593096
Biomater Sci. 2025 May 16.

In vitro senescence and senolytic functional assays.

Patrick Ryan, Jungwoo Lee.

A detailed understanding of aging biology and the development of anti-aging therapeutic strategies remain imperative yet inherently challenging due to the protracted nature of aging. Cellular senescence arises naturally through replicative exhaustion and is accelerated by clinical treatments or environmental stressors. The accumulation of senescent cells-defined by a loss of mitogenic potential, resistance to apoptosis, and acquisition of a pro-inflammatory secretory phenotype-has been implicated as a key driver of chronic disease, tissue degeneration, and organismal aging. Recent studies have highlighted the therapeutic promise of senolytic drugs, which selectively eliminate senescent cells. Compelling results from preclinical animal studies and ongoing clinical trials underscore this potential. However, the clinical translation of senolytics requires further pharmacological validation to refine selectivity, minimize toxicity, and determine optimal dosing. Equally important is the evaluation of senolytics' potential to restore tissue structure and function by reducing the senescent cell burden. In vitro tissue culture models offer a powerful platform to advance these efforts. This review summarizes the current landscape of in vitro systems used for inducing cellular senescence-referred to as "senescence assays"-and for screening senolytic drugs-referred to as "senolytic assays". We conclude by discussing key challenges to improving mechanistic insight, predictive accuracy, and clinical relevance in senolytic drug development, as well as emerging applications of senolytic therapies.

DOI: https://doi.org/10.1039/d4bm01684j
bioRxiv. 2025 May 03. pii: 2025.05.01.651651. [Epub ahead of print]

Age-related declines in niche self-renewal factors controls testis aging and spermatogonial stem cell competition through Hairless, Imp, and Chinmo.

Yu Zheng, Ya-Chien Lee, Yu-Ting Wang, Pin-Kuan Chiang, Shao-Lun Chang, Hwei-Jan Hsu, Li-Sung Hsu, Erika A Bach, Chen-Yuan Tseng.

Aging is associated with progressive tissue decline and shifts in stem cell clonality. The role of niche signals in driving these processes remains poorly understood. Using the Drosophila testis, we identify a regulatory axis in which age-related decline of niche signals (BMPs) lead to upregulation of the co-repressor Hairless, which downregulates the RNA-binding protein Imp in aged germline stem cells (GSCs). Reduced Imp causes loss of Chinmo, a key factor in GSC aging and competition. Reduced Chinmo causes ectopic Perlecan secretion which accumulates in the testis lumen and causes GSC loss. Aging of the testis is reversed by increasing BMPs in the niche, or by overexpressing Imp or depleting Hairless in GSCs. Furthermore, GSC clones with reduced Imp or increased Hairless are more competitive, expelling wild-type neighbors and monopolizing the niche. Thus, BMPs regulate testicular niche aging through the Hairless-Imp-Chinmo axis and "winning" GSCs usurp these aging mechanisms.
Highlights: Aged niche cells produce less BMPs, resulting in more Hairless (H) in aged GSCs Elevated H represses Imp , resulting in less Chinmo and in ectopic ECM secretion Aging is prevented by higher BMP in niche cells, or by higher Imp or lower H in GSCs GSCs with low Imp or high H exploit these aging mechanisms to colonize the GSC pool.

DOI: https://doi.org/10.1101/2025.05.01.651651
Genomics Proteomics Bioinformatics. 2025 May 12. pii: qzaf044. [Epub ahead of print]

CircAge: A Comprehensive Resource for Aging-associated Circular RNAs Across Species and Tissues.

Xin Dong, Zhen Zhou, Yanan Wang, Ayesha Nisar, Shaoyan Pu, Longbao Lv, Yijiang Li, Xuemei Lu, Yonghan He.

  Circular RNAs (circRNAs) represent a novel class of RNA molecules characterized by a circular structure and enhanced stability. Emerging evidence indicates that circRNAs play pivotal regulatory roles in the aging process. Despite this, there is a lack of a systematic resource that integrates aging-associated circRNA data. Therefore, we developed a comprehensive database named CircAge, which encompasses 803 aging-related samples from 7 species and 24 tissue types. Through high-throughput sequencing, we also generated 47 new tissue samples from mice and rhesus monkeys. Integrating predictions from multiple bioinformatics tools, we identified over 529,856 unique circRNAs. Our data analysis revealed a general increase in circRNA expression levels with age, with approximately 23% of circRNAs demonstrating sequence conservation across species. The CircAge database systematically predicts potential interactions between circRNAs, microRNAs (miRNAs), and RNA-binding proteins (RBPs), and assesses the coding potential of circRNAs. This resource lays a foundation for elucidating the regulatory mechanisms of circRNAs in aging. As a comprehensive repository of aging-associated circRNAs, CircAge will significantly accelerate research in this field, facilitating the discovery of novel biomarkers and therapeutic targets for aging biology and developing diagnostic and therapeutic strategies for aging and age-related diseases. CircAge is publicly available at https://circage.kiz.ac.cn.

Keywords:  Aging; Database; RNA-binding protein; circRNA; miRNA

DOI:  https://doi.org/10.1093/gpbjnl/qzaf044
Aging Dis. 2025 Apr 25.

Lanatoside C, a Novel Senolytic, Ameliorates Atherosclerosis in Mice.

Eok-Cheon Kim, Youlim Son, Seon-Hui Kim, Soo-Ji Kim, So-Young Park, Jae-Ryong Kim.

Cellular senescence, a state of irreversible cell cycle arrest, contributes to aging and age-related diseases. Senolytics targeting cellular senescence could be applied to the prevention and treatment of age-related diseases. In this study, we identified lanatoside C (Lana C) as a senolytic compound. Lana C, a cardiac glycoside used for the treatment of cardiovascular diseases, is known to inhibit the transmembrane protein sodium-potassium adenosine triphosphatase (Na+/K+-ATPase). We found that Lana C depolarized and acidified senescent human umbilical vein endothelial cells (HUVECs), making them susceptible to apoptosis. The senolytic activity of Lana C was inhibited by potassium chloride (KCl) and Z-VAD-FMK (ZVF), a widely used pan-caspase inhibitor. Additionally, Lana C significantly ameliorated the senescence burden and the formation of atherosclerotic lesions in apolipoprotein E (ApoE-/-) or low-density lipoprotein receptor (Ldlr-/-) knockout mice. These results suggest that Lana C could be a promising senolytic for age-related diseases.

DOI: https://doi.org/10.14336/AD.2025.1219
Aging Cell. 2025 May 15. e70105

hTERT Increases TRF2 to Induce Telomere Compaction and Extend Cell Replicative Lifespan.

Nancy Adam, Yang Yang, Mahbod Djamshidi, Sara Seifan, Nicholas S Y Ting, Joel Glover, Nicolas Touret, Paul M K Gordon, K V Vineetha Warriyar, Hokan Krowicki, Christine Kim Garcia, Sharon A Savage, Aaron A Goodarzi, Duncan M Baird, Tara L Beattie, Karl Riabowol.

  Replicative senescence occurs in response to shortened telomeres and is triggered by ATM and TP53-mediated DNA damage signaling that blocks replication. hTERT lengthens telomeres, which is thought to block damage signaling and the onset of senescence. We find that normal diploid fibroblasts expressing hTERT mutants unable to maintain telomere length do not initiate DNA damage signaling and continue to replicate, despite having telomeres shorter than senescent cells. The TRF1 and TRF2 DNA binding proteins of the shelterin complex stabilize telomeres, and we find that expression of different mutant hTERT proteins decreases levels of the Siah1 E3 ubiquitin ligase that targets TRF2 to the proteasome, by increasing levels of the CDC20 and FBXO5 E3 ligases that target Siah1. This restores the TRF2:TRF1 ratio to block the activation of ATM and subsequent activation of TP53 that is usually associated with DNA damage-induced senescence signaling. All hTERT variants reduce DNA damage signaling, and this occurs concomitantly with telomeres assuming a more compact, denser conformation than senescent cells as measured by super-resolution microscopy. This indicates that hTERT variants induce TRF2-mediated telomere compaction that is independent of telomere length, and it plays a dominant role in regulating the DNA damage signaling that induces senescence and blocks replication of human fibroblasts. These observations support the idea that very short telomeres often seen in cancer cells may fail to induce senescence due to selective stabilization of components of the shelterin complex, increasing telomere density, rather than maintaining telomere length via the reverse transcriptase activity of hTERT.

Keywords:  TRF2 stabilization; hTERT noncanonical activity; senescence; telomere clustering; telomere compaction

DOI:  https://doi.org/10.1111/acel.70105
Aging Cell. 2025 May 15. e70107

Ythdf2 Ablation Protects Aged Retina From RGC Dendrite Shrinking and Visual Decline.

Fugui Niu, Gaoxin Long, Jian Zhang, Jun Yu, Sheng-Jian Ji.

  Aging-related retinal degeneration and vision loss have been severely affecting the elderly worldwide. Previously, we showed that the m6A reader YTHDF2 is a negative regulator for dendrite development and protection of retinal ganglion cells (RGC) in mice. Here, we further show that conditional ablation of Ythdf2 protects the retina from RGC dendrite shrinking and vision loss in aged mice. Additionally, we identify Hspa12a and Islr2 as the potential YTHDF2 target mRNAs mediating these effects. Together, our results indicate that the m6A reader YTHDF2 regulates retinal degeneration caused by aging, which might provide important therapeutic potential for developing new treatment approaches against aging-related vision loss.

Keywords:  YTHDF2; aging; dendrite; m6A; retinal degeneration; visual acuity

DOI:  https://doi.org/10.1111/acel.70107
Mol Nutr Food Res. 2025 May 12. e70088

Telomeres and Telomerase: Targets for Chemoprevention of Hepatocellular Carcinoma With Bioactive Food Compounds.

Juliana Marques Affonso, Thais Pereira D'Amico, Maria Aderuza Horst, Fernando Salvador Moreno, Renato Heidor.

  The maintenance of telomere length by telomerase plays an essential role in senescence, aging, and cancer. Mutations in the TERT promoter, a telomerase subunit, are frequent in human cancers. In hepatocellular carcinoma (HCC), telomere shortening contributes to preneoplastic conditions such as cirrhosis. Telomerase activation during cirrhosis may reduce chromosomal instability, while its suppression in early dysplastic nodules may prevent hepatocarcinogenesis. Evidence suggests that bioactive food compounds (BFCs) can reduce the incidence and/or delay the onset of HCC by modulating telomerase activity. A systematic review was conducted on the role of BFCs in telomerase activity during hepatocarcinogenesis. BFCs were analyzed in isolated form or as part of extracts and categorized into fatty acids, isoprenoids, isothiocyanates, and phenolic compounds. Despite structural diversity, BFCs modulate telomerase through common mechanisms, including inhibition of activating proteins at the TERT promoter, activation of nuclear receptors, or histone H3 hyperacetylation. Indirectly, telomerase can also be modulated via activation of antioxidant defense pathways. Understanding telomerase reactivation and its modulation by BFCs is key to establishing effective HCC chemoprevention strategies targeting telomerase.

Keywords:  cancer; functional foods; polyphenols; prevention

DOI:  https://doi.org/10.1002/mnfr.70088
Aging Med (Milton). 2025 Apr;8(2): 145-155

PseudoCell: A Multivalued Logical Regulatory Network to Investigate Premature Senescence Dynamics and Heterogeneity.

Vinícius Pierdoná, Patrícia Lavandoski, Rafael Moura Maurmann, Guilherme Antônio Borges, Jose Carlos Merino Mombach, Fátima Theresinha Costa Rodrigues Guma, Florencia María Barbé-Tuana.

   Purpose: Premature cellular senescence is a pivotal process in aging and age-related diseases, triggered by various stressors. However, this is not a homogeneous phenotype, but a heterogeneous cellular state composed of multiple senescence programs with different compositions. Therefore, understanding the complex dynamics of senescence programs requires a systemic approach. We introduce PseudoCell, a multivalued logical regulatory network designed to explore the molecular intricacies of premature senescence.
Methods: PseudoCell integrates key senescence signaling pathways and molecular mechanisms, offering a versatile platform for investigating diverse premature senescence programs initiated by different stimuli.
Results: Validation through simulation of classical senescence programs, including oxidative stress-induced senescence and oncogene-induced senescence, demonstrates its ability to replicate molecular signatures consistent with empirical data. Additionally, we explore the role of CCL11, a novel senescence-associated molecule, through simulations that reveal potential pathways and mechanisms underlying CCL11-mediated senescence induction.
Conclusions: In conclusion, PseudoCell provides a systematic approach to dissecting premature senescence programs and uncovering novel regulatory mechanisms.

Keywords:  aging; bioinformatics; cellular senescence; in silico modeling; premature senescence

DOI:  https://doi.org/10.1002/agm2.70020
Int J Mol Sci. 2025 May 05. pii: 4382. [Epub ahead of print]26(9):

Body Fluid-Derived Stem Cells: Powering Innovative, Less-Invasive Cell Therapies.

Adam David Goff, Xinyue Zhang, Biju Thomas, Sally Shin Yee Ong, Anthony Atala, Yuanyuan Zhang.

  Stem cell therapy offers significant promise for tissue regeneration and repair. Traditionally, bone marrow- and adipose-derived stem cells have served as primary sources, but their clinical use is limited by invasiveness and low cell yield. This review focuses on body fluid-derived stem cells as an emerging, non-invasive, and readily accessible alternative. We examine stem cells isolated from amniotic fluid, peripheral blood, cord blood, menstrual fluid, urine, synovial fluid, breast milk, and cerebrospinal fluid, highlighting their unique biological properties and therapeutic potential. By comparing their characteristics and barriers to clinical translation, we propose body fluid-derived stem cells as a promising source for regenerative applications, with continued research needed to fully achieve their clinical utility.

Keywords:  body fluid-derived stem cells; personalized medicine; regeneration; stem cell therapy

DOI:  https://doi.org/10.3390/ijms26094382
Front Pharmacol. 2025 ;16 1543277

SuoquanYishen formula improves renal cellular senescence by inhibiting YTHDF1-Rubicon axis to promote autophagy in diabetic kidney disease.

Zijie Yan, Lin Zhang, Tianpeng Ma, Yong Yuan, Yu Kang, Shuman Liu, BoCen Chen, Kai Li, Man Xiao, Yiqiang Xie.

  SuoquanYishen formula (SQYSF), a traditional Chinese herbal prescription for treating diabetic kidney disease (DKD), has demonstrated clinical efficacy in lowering blood glucose and alleviating renal damage. Emerging evidence implicates cellular senescence as a critical contributor to DKD progression. This study aimed to elucidate the mechanism by which SQYSF improves renal cellular senescence using both in vivo (db/db mice) and in vitro (high glucose-induced HK-2 cells) DKD models, with interventions involving SQYSF aqueous extract and SQYSF-containing serum. We screened 59 chemical compounds by UHPLC-QTOF-MS and used network pharmacology approach to discover that autophagy and cellular senescence are important pathways for pharmacological treatment of disease. Experimental validation demonstrated that senescence and damage occurred in the kidneys of db/db mice and HK-2 cells under high glucose environment, and SQYSF ameliorated these abnormal changes. Then, we also found that SQYSF enhanced autophagy in renal tissues and cells, whereas co-treatment with the autophagy inhibitor Bafilomycin A1 abolished SQYSF's anti-senescence effects. Notably, DKD progression was associated with elevated Rubicon expression at mRNA and protein levels, accompanied by increased m6A modification. While SQYSF effectively downregulated Rubicon mRNA and protein expression, it did not influence m6A modification levels. Further investigation identified that SQYSF was able to target to reduce YTHDF1 expression level. Overexpression of YTHDF1 in HK-2 cells increased Rubicon mRNA stability and protein expression, while concurrently reversing SQYSF-induced autophagy enhancement and senescence amelioration. These results suggest that SQYSF exerts its role in ameliorating renal cellular senescence in DKD by targeting to reduce the expression level of YTHDF1, which inhibits the level of Rubicon mRNA and protein translation, and thus promotes autophagy. Our results reveal the active components and mechanisms of SQYSF for the treatment of DKD, which may provide useful information to guide the clinical application of SQYSF as well as the therapeutic pathway for DKD.

Keywords:  Rubicon; SuoquanYishen formula; YTHDF1; autophagy; cellular senescence; diabetic kidney disease; m6A modification; traditional Chinese medicine

DOI:  https://doi.org/10.3389/fphar.2025.1543277
Int Immunopharmacol. 2025 May 11. pii: S1567-5769(25)00803-3. [Epub ahead of print]158 114813

Exosomes derived from human umbilical cord mesenchymal stem cells attenuate senescence of peritoneal mesothelial cells by inhibiting oxidative stress.

Jia Li, Lixin Liu, Yiman Chen, Yuling Huang, Lina Yang.

   OBJECTIVE: Aging is a natural process that affects cellular function. In peritoneal dialysis (PD), chronic exposure to dialysate induces oxidative stress (OS) in peritoneal mesothelial cells (PMCs), leading to cellular aging, fibrosis, and reduced dialysis efficacy. Mesenchymal stem cells (MSCs) have shown potential in alleviating cellular aging. This study investigates the role of exosomes (hUMSC-Exos) derived from human umbilical cord MSCs (hUMSCs) in mitigating PMC senescence and explores the underlying mechanisms.
METHODS: Human peritoneal mesothelial cells (HMrSV5) were cultured with 2.5 % glucose to induce senescence. Aging markers were assessed via Western blotting, β-galactosidase staining, and cell cycle analysis. hUMSC-Exos were characterized using Western blot, electron microscopy, and nanoparticle tracking analysis. Their uptake by HMrSV5 cells was confirmed through fluorescence microscopy. Various concentrations of hUMSC-Exos were tested, and OS levels were evaluated using reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) assays. The impact of the OS inhibitor N-acetyl-L-cysteine (NAC) on aging markers was also examined.
RESULTS: HMrSV5 cells treated with 2.5 % glucose exhibited increased expression of P53, P21, and P16, along with G0/G1 cell cycle arrest. Treatment with 150 μg/mL hUMSC-Exos reduced aging markers, decreased ROS and MDA levels, and increased SOD activity. Similar effects were observed with NAC treatment.
CONCLUSION: hUMSC-Exos alleviate PMCs aging by inhibiting OS, highlighting their potential to improve PD outcomes.

Keywords:  Aging; Exosomes; Mesenchymal stem cells; Oxidative stress

DOI:  https://doi.org/10.1016/j.intimp.2025.114813
Aging Dis. 2025 Apr 22.

Lysosomes as Dynamic Regulators of Metabolic Signaling and Organ Physiology in Aging: From Mechanism to Therapy.

Yu Sun, Jin Wei, Shiyin Ma, Chang He, Liutao Sui, Xudong Pan, Xiaoyan Zhu.

Lysosomes are degradation centers and signaling hubs that in cells and play important roles in cellular homeostasis, development, and aging. Growing evidence has also implicated the role of lysosome-related mechanisms in the aging process. Meanwhile, the potential impact of lysosomal dysfunction on the production of inflammatory molecules, cellular metabolic status, and mitochondrial function is becoming increasingly significant. In this review, we provide a comprehensive overview of the physiological roles of lysosomes and their association with aging. At the cellular level, lysosomal dysfunction and cellular senescence show strong correlations. Herein, we elucidated the precise mechanisms by which lysosomal dysfunction contributes to various cellular physiological processes, as well as its potential implications in age-related hallmarks. More importantly, we discuss how lysosomal homeostasis is disrupted in several age-related diseases, including atherosclerosis, heart diseases, cancer, neurodegenerative diseases, metabolic disorders, and motor system diseases. Thus, a deeper understanding of lysosomal function may provide fundamental insights into human physiology and age-related diseases. Furthermore, these discoveries emphasize the role of the lysosome in the development of novel therapeutic strategies.

DOI: https://doi.org/10.14336/AD.2025.0275
Exp Cell Res. 2025 May 13. pii: S0014-4827(25)00199-5. [Epub ahead of print] 114603

Testicular aging: mechanism, management and future therapy.

Jing Zhou, Qiang Dong.

  Testicular aging results in degeneration in testicular function, including decreased testosterone production and quality of sperm. Decreased testosterone level is associated with a range of systemic diseases and comorbidities, including cardiovascular disease, cognitive decline, depression, osteoporosis, frailty, increased body fat, and metabolic syndrome. In addition, with the rapid development of industrialization and increasing environmental pollution, the quality of male semen continues to decline globally. Currently, the average age of first marriage and childbirth for men is delayed, and the birth rate has been declining year by year. At present, the therapies for testosterone level decline in clinical practice are relatively limited. Therefore, studying the triggering and delaying mechanisms of testicular aging is significant for improving male health and protecting male fertility. This review summarizes the mechanisms and treatment strategies for male reproductive aging.

Keywords:  Androgen deficiency; Reproductive Health; Senescence; Testicular aging

DOI:  https://doi.org/10.1016/j.yexcr.2025.114603
Aging Cell. 2025 May 15. e70079

The Redox Activity of Protein Disulphide Isomerase Functions in Non-Homologous End-Joining Repair to Prevent DNA Damage.

Sina Shadfar, Fabiha Farzana, Sayanthooran Saravanabavan, Ashley M Rozario, Marta Vidal, Cyril Jones Jagaraj, Sonam Parakh, Esmeralda Paric, Kristy C Yuan, Mariana Brocardo, Donna R Whelan, Angela S Laird, Julie D Atkin.

  DNA damage is a serious threat to cellular viability, and it is implicated as the major cause of normal ageing. Hence, targeting DNA damage therapeutically may counteract age-related cellular dysfunction and disease, such as neurodegenerative conditions and cancer. Identifying novel DNA repair mechanisms therefore reveals new therapeutic interventions for multiple human diseases. In neurons, non-homologous end-joining (NHEJ) is the only mechanism available to repair double-stranded DNA breaks (DSB), which is much more error prone than other DNA repair processes. However, there are no therapeutic interventions to enhance DNA repair in diseases affecting neurons. NHEJ is also a useful target for DNA repair-based cancer therapies to selectively kill tumour cells. Protein disulphide isomerase (PDI) participates in many diseases, but its roles in these conditions remain poorly defined. PDI exhibits both chaperone and redox-dependent oxidoreductase activity, and while primarily localised in the endoplasmic reticulum it has also been detected in other cellular locations. We describe here a novel role for PDI in DSB repair following at least two types of DNA damage. PDI functions in NHEJ, and following DNA damage, it relocates to the nucleus, where it co-localises with critical DSB repair proteins at DNA damage foci. A redox-inactive mutant of PDI lacking its two active site cysteine residues was not protective, however. Hence, the redox activity of PDI mediates DNA repair, highlighting these cysteines as targets for therapeutic intervention. The therapeutic potential of PDI was also confirmed by its protective activity in a whole organism against DNA damage induced in vivo in zebrafish. Hence, harnessing the redox function of PDI has potential as a novel therapeutic target against DSB DNA damage relevant to several human diseases.

Keywords:  DNA damage; DNA repair; ageing; cancer; double‐stranded DNA breaks; neurodegenerative conditions; zebrafish

DOI:  https://doi.org/10.1111/acel.70079
Zhongguo Zhong Yao Za Zhi. 2025 Feb;50(4): 1063-1074

[Network pharmacology and animal experiments reveal molecular mechanisms of Cordyceps sinensis in ameliorating heart aging and injury in mice by regulating Nrf2/HO-1/NF-κB pathway].

Si-Yi Liu, Yue Tu, Wei-Ming He, Wen-Jie Liu, Kai-Zhi Wen, Cheng-Juan Li, Chao Han, Xin-Yu Liang.

  This study aims to explore the effects and mechanisms of the traditional Chinese medicine Cordyceps sinensis(CS) in ameliorating heart aging and injury in mice based on animal experiments and network pharmacology. A mouse model of heart aging was established by continuously subcutaneous injection of D-galactose(D-gal). Thirty mice were randomly assigned into a normal group, a model group, a low-dose CS(CS-L) group, a high-dose CS(CS-H) group, and a vitamin E(VE) group. Mice in these groups were administrated with normal saline, different doses of CS suspension, or VE suspension via gavage daily. After 60 days of treatment with D-gal and various drugs, all mice were euthanized, and blood and heart tissue samples were collected for determination of the indicators related to heart aging and injury in mice. Experimental results showed that both high and low doses of CS and VE ameliorated the aging phenotype, improved the heart index and myocardial enzyme spectrum, restored the expression levels of proteins associated with cell cycle arrest and senescence-associated secretory phenotypes(SASP), and alleviated the fibrosis and histopathological changes of the heart tissue in model mice. From the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),259 active ingredients of CS were retrieved. From Gene Cards and OMIM, 2 568 targets related to heart aging were identified, and 133common targets shared by CS and heart aging were obtained. The Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment revealed that the pathways related to heart aging involved oxidative stress,apoptosis, inflammation-related signaling pathways, etc. The animal experiment results showed that both high and low doses of CS and VE ameliorated oxidative stress and apoptosis in the heart tissue to varying degrees in model mice. Additionally, CS-H and VE activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and inhibited the expression of key proteins in the nuclear factor-κB(NF-κB) pathway in the heart tissue of model mice. In conclusion, this study demonstrated based on network pharmacology and animal experiments that CS may alleviate heart aging and injury in aging mice by reducing oxidative stress,apoptosis, and inflammation in the heart via the Nrf2/HO-1/NF-κB pathway.

Keywords:  Cordyceps sinensis; Nrf2/HO-1/NF-κB pathway; apoptosis; heart aging and injury; network pharmacology; oxidative stress

DOI:  https://doi.org/10.19540/j.cnki.cjcmm.20241014.701
Hum Gene Ther. 2025 May 12.

Progress, Applications and Prospects of CRISPR-Based Genome Editing Technology in Gene Therapy for Cancer and Sickle Cell Disease.

Sha-Sha Zang, Ruirui Zhang, Jia-Run Zhang, Xi Zhang, Jun Li.

  The advent of genome-editing technologies, particularly the RNA-guided the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system (Cas) 9, which originates from prokaryotic CRISPR/Cas adaptive immune mechanisms, has revolutionized molecular biology. Renowned for its simplicity, cost-effectiveness, and capacity for multiplexed gene editing, CRISPR/Cas9 has emerged as the most versatile and widely adopted genome-editing platform. Its applications span fundamental research, biotechnology, medicine, and therapeutics. This review highlights recent advancements in CRISPR-based technologies, focusing on CRISPR/Cas9, CRISPR/Cas12a, and CRISPR/Cas12f. It emphasizes precision editing methods like base editing and prime editing, which enable targeted nucleotide changes without double-strand breaks. The specificity of these tools, including on-target accuracy and off-target risks, is critically evaluated. Additionally, recent preclinical and clinical efforts to treat diseases such as cancer and sickle cell disease using CRISPR are summarized. Finally, the challenges and future directions of CRISPR-mediated gene therapy are discussed, emphasizing its potential to integrate with other molecular approaches to address unmet medical needs.

Keywords:  CRISPR; base editing; cancer; prime editing; sickle cell disease; β-thalassemia

DOI:  https://doi.org/10.1089/hum.2024.262