bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2025–03–02
53 papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño
  1. Identification of senescence rejuvenation mechanism of Magnolia officinalis extract including honokiol as a core ingredient.
  2. Recent Advances in Anti-Aging Therapeutic Strategies Targeting DNA Damage Response and Senescence-Associated Secretory Phenotype-Linked Signaling Cascade.
  3. The Potential of Polyphenols in Modulating the Cellular Senescence Process: Implications and Mechanism of Action.
  4. Evolutionary Insights into Irisin/FNDC5: Roles in Aging and Disease from Drosophila to Mammals.
  5. Oral Transfer of Anti-Aging Substances: Key Chemical Found in Reproductive Caste of Termites.
  6. Klotho protects INS-1 pancreatic β-cells from senescence and enhances mitochondrial function.
  7. The Anti-Aging Mechanism of Metformin: From Molecular Insights to Clinical Applications.
  8. Antioxidant Senotherapy by Natural Compounds: A Beneficial Partner in Cancer Treatment.
  9. Hypoxia-inducible factor and cellular senescence in pulmonary aging and disease.
  10. Secretome from HMGB1 Box A-over-expressing Adipose-derived Stem Cells Shows Potential for Skin Rejuvenation by Senescence Reversal in PM2.5-induced Senescence Cells via Stem Cell Induction.
  11. UFMylation maintains YAP stability to promote vascular endothelial cell senescence.
  12. Long-term effects of s-KL treatment in wild-type mice: enhancing longevity, physical well-being, and neurological resilience.
  13. 37 kDa LRP::FLAG enhances telomerase activity and reduces ageing markers in vivo.
  14. Lysine-specific demethylase 1 (LSD1) suppresses cellular senescence by riboflavin uptake-dependent demethylation activity.
  15. Circular RNA Telomerase Reverses Endothelial Senescence in Progeria.
  16. Ganodermalucidum Extract Modulates Gene Expression Profiles Associated with Antioxidant Defense, Cytoprotection, and Senescence in Human Dermal Fibroblasts: Investigation of Quantitative Gene Expression by qPCR.
  17. Effects of Silibinin on Delaying Aging in Drosophila melanogaster.
  18. Cellular Senescence in Health, Disease, and Lens Aging.
  19. Human umbilical cord mesenchymal stem cell-derived exosome ameliorate doxorubicin-induced senescence.
  20. Endocrine Controls of Skin Aging.
  21. The role of different physical exercises as an anti-aging factor in different stem cells.
  22. Perception and Longevity Control in Invertebrate Model Organisms-A Mini-Review of Recent Advances.
  23. POLLUTION, A RELEVANT EXPOSOME FACTOR IN SKIN AGING AND THE ROLE OF MULTI-BENEFIT PHOTOPROTECTION.
  24. Anti-Aging Potential of Avocado Oil via Its Antioxidant Effects.
  25. The Role of Extracellular Vesicles in Aging and Age-Related Disorders.
  26. Anthocyanin-Binding Affinity and Non-Covalent Interactions with IIS-Pathway-Related Protein Through Molecular Docking.
  27. Improvement of Skin Condition Through RXR Alpha-Activating Materials.
  28. Update of cellular senescence in kidney fibrosis: from mechanism to potential interventions.
  29. Hallmarks of ovarian aging.
  30. Exploring Anti-Aging Effects of Topical Treatments for Actinic Keratosis.
  31. The Power of Environment: A Comprehensive Review of the Exposome's Role in Healthy Aging, Longevity, and Preventive Medicine-Lessons from Blue Zones and Cilento.
  32. Effective release of Eryngium maritimum L. callus extract via encapsulation in multilayered liposomes for skin delivery.
  33. The Potential of Superoxide Dismutase-Rich Tetraselmis chuii as a Promoter of Cellular Health.
  34. Low molecular weight protein tyrosine phosphatase: A driver of lipid metabolic remodeling in Caenorhabditis elegans.
  35. Effects of senotherapeutics on gut microbiome dysbiosis and intestinal inflammation in Crohn's disease: A pilot study.
  36. Extraction Optimization and Bioactivity of Polysaccharides from Ganoderma leucocontextum Spores.
  37. Protective Effects of Centella asiatica Against Senescence and Apoptosis in Epidermal Cells.
  38. Thymoquinone-Loaded Chitosan Nanoparticles Combat Testicular Aging and Oxidative Stress Through SIRT1/FOXO3a Activation: An In Vivo and In Vitro Study.
  39. Advances in regenerative medicine-based approaches for skin regeneration and rejuvenation.
  40. Awareness, knowledge, and motivations about lifespan, healthspan, and Healthy Longevity Medicine in the general population: the HEalthy LOngevity (HELO) conceptual framework.
  41. Harnessing the FOXO-SIRT1 axis: insights into cellular stress, metabolism, and aging.
  42. Efficacy of Naringenin against aging and degeneration of nucleus pulposus cells through IGFBP3 inhibition.
  43. Dietary nitrate supplementation mitigates age-related changes at the neuromuscular junction in mice.
  44. Restoring neuropetide Y levels in the hypothalamus ameliorates premature aging phenotype in mice.
  45. Lactobacillus-derived artificial extracellular vesicles for skin rejuvenation and prevention of photo-aging.
  46. Fetal adnexa-derived allogeneic mesenchymal stem cells for cardiac regeneration: the future trend of cell-based therapy for age-related adverse conditions.
  47. Plant-Derived Nanovesicles as Novel Nanotherapeutics for Alleviating Endothelial Cell Senescence-Associated Vascular Remodeling Induced by Hypertension.
  48. Occurrence of cellular senescence in chronic human shoulder tendinopathies and its attenuation ex vivo by inhibition of Enhancer of Zeste 2.
  49. N-benzyl-N-methyldecane-1-amine derived from garlic ameliorates UVB-induced photoaging in HaCaT cells and SKH-1 hairless mice.
  50. Discovering the Potential of Cannabidiol for Cosmeceutical Development at the Cellular Level.
  51. Autophagy regulates cellular senescence by mediating the degradation of CDKN1A/p21 and CDKN2A/p16 through SQSTM1/p62-mediated selective autophagy in myxomatous mitral valve degeneration.
  52. Selectively Blocking Small Conductance Ca2+-Activated K+ Channels Improves Cognition in Aged Mice.
  53. Preventive Pathways for Healthy Ageing: A Systematic Literature Review.
  1. Aging (Albany NY). 2025 Feb 21. 17
    Identification of senescence rejuvenation mechanism of Magnolia officinalis extract including honokiol as a core ingredient.
    Yun Haeng Lee, Eun Young Jeong, Ye Hyang Kim, Ji Ho Park, Jee Hee Yoon, Yoo Jin Lee, So Hun Lee, Yeon Kyung Nam, So Yoon Cha, Jin Seong Park, So Yeon Kim, Youngjoo Byun, Song Seok Shin, Joon Tae Park.
      Reactive oxygen species (ROS) contribute to aging by mainly damaging cellular organelles and DNA. Although strategies to reduce ROS production have been proposed as important components of anti-aging therapy, effective mechanisms to lower ROS levels have not yet been identified. Here, we screened natural compounds frequently used as cosmetic ingredients to find substances that reduce ROS levels. Magnolia officinalis (M. officinalis) extract significantly lowered the levels of ROS in senescent fibroblasts. A novel mechanism by which M. officinalis extract restores mitochondrial function to reduce ROS, a byproduct of inefficient electron transport, was discovered. The reduction of ROS by M. officinalis extracts reversed senescence-associated phenotypes and skin aging. Then, honokiol was demonstrated as a core ingredient of M. officinalis extract that exhibits antioxidant effects. Honokiol functions as an oxygen radical scavenger through redox processes, also significantly reduced ROS levels by restoring mitochondrial function. In summary, our study identified a novel mechanism by which M. officinalis extract reverses aging and skin aging by reducing ROS through restoring mitochondrial function. These new findings will not only expand our understanding of aging and associated diseases, but also provide new approaches to anti-aging treatments.
    Keywords:  ROS; aging rejuvenation; honokiol; magnolia officinalis; mitochondria
    DOI:  https://doi.org/10.18632/aging.206207
  2. Cell Biochem Funct. 2025 Mar;43(3): e70046
    Recent Advances in Anti-Aging Therapeutic Strategies Targeting DNA Damage Response and Senescence-Associated Secretory Phenotype-Linked Signaling Cascade.
    Jawad Nadeem, Razia Sultana, Amna Parveen, Sun Yeou Kim.
      Aging is considered the contributory accumulation of abruptions occurring through cell signaling cascades, which ultimately cause changes in physical functions, cell fate, and damage across all organ systems. DNA damage response (DDR) also occurs through telomere shortening, tumor formation, mitochondrial dysfunction, and so forth. Cellular aging occurs through cell cycle arrest, which is the result of extended DDR cascade signaling networks via MDC1, 53BP1, H2AX, ATM, ARF, P53, P13-Akt, BRAF, Sirtuins, NAD + , and so forth. These persistent cell cycle arrests initiated by DDR and other associated stress-induced signals promote a permanent state of cell cycle arrest called senescence-associated secretory phenotype (SASP). However, cellular aging gets accelerated with faulty DNA repair systems, and the produced senescent cells further generate various promoting contributors to age-related dysfunctional diseases including SASP. Any changes to these factors contribute to age-related disease development. Therefore, this review explores anti-aging factors targeting DDR and SASP regulation and their detailed signaling networks. In addition, it allows researchers to identify anti-aging targets and anti-aging therapeutic strategies based on identified and nonidentified targets.
    Keywords:  DNA damage response; antiaging therapeutic strategies; anti‐aging; cell signaling cascades; senescence‐associated secretory phenotype
    DOI:  https://doi.org/10.1002/cbf.70046
  3. Pharmaceuticals (Basel). 2025 Jan 22. pii: 138. [Epub ahead of print]18(2):
    The Potential of Polyphenols in Modulating the Cellular Senescence Process: Implications and Mechanism of Action.
    Larissa Della Vedova, Giovanna Baron, Paolo Morazzoni, Giancarlo Aldini, Francesca Gado.
      Background: Cellular senescence is a biological process with a dual role in organismal health. While transient senescence supports tissue repair and acts as a tumor-suppressive mechanism, the chronic accumulation of senescent cells contributes to aging and the progression of age-related diseases. Senotherapeutics, including senolytics, which selectively eliminate senescent cells, and senomorphics, which modulate the senescence-associated secretory phenotype (SASP), have emerged as promising strategies for managing age-related pathologies. Among these, polyphenols, a diverse group of plant-derived bioactive compounds, have gained attention for their potential to modulate cellular senescence. Methods: This review synthesizes evidence from in vitro, in vivo, and clinical studies on the senolytic and senomorphic activities of bioactive polyphenols, including resveratrol, kaempferol, apigenin, and fisetin. The analysis focuses on their molecular mechanisms of action and their impact on fundamental aging-related pathways. Results: Polyphenols exhibit therapeutic versatility by activating SIRT1, inhibiting NF-κB, and modulating autophagy. These compounds demonstrate a dual role, promoting the survival of healthy cells while inducing apoptosis in senescent cells. Preclinical evidence indicates their capacity to reduce SASP-associated inflammation, restore tissue homeostasis, and attenuate cellular senescence in various models of aging. Conclusions: Polyphenols represent a promising class of senotherapeutics for mitigating age-related diseases and promoting healthy lifespan extension. Further research should focus on clinical validation and the long-term effects of these compounds, paving the way for their development as therapeutic agents in geriatric medicine.
    Keywords:  cellular senescence; polyphenols; senolytic; senomorphic
    DOI:  https://doi.org/10.3390/ph18020138
  4. Biomolecules. 2025 Feb 11. pii: 261. [Epub ahead of print]15(2):
    Evolutionary Insights into Irisin/FNDC5: Roles in Aging and Disease from Drosophila to Mammals.
    Kiwon Lee, Myungjin Kim.
      The Irisin/FNDC5 protein family has emerged as a pivotal link between exercise and the prevention of age-associated diseases. Irisin is highly expressed during exercise from skeletal and cardiac muscle cells, playing a critical role in mediating systemic health benefits through its actions on various tissues. However, Irisin levels decline with age, correlating with a heightened incidence of diseases such as muscle weakness, cardiovascular disorders, and neurodegeneration. Notably, the administration of Irisin has shown significant potential in both preventing and treating these conditions. Recently, an Irisin/FNDC5 homolog was identified in an invertebrate Drosophila model, providing valuable insights into its conserved role in exercise physiology. Importantly, Irisin/FNDC5 has been demonstrated to regulate autophagy-a process essential for clearing excessive nutrients, toxic aggregates, and dysfunctional organelles-in both flies and mammals. Dysregulated autophagy is often implicated in age-related diseases, highlighting its relevance to Irisin/FNDC5's functions. These findings deepen our understanding of Irisin/FNDC5's roles and its potential as a therapeutic target for mitigating aging-related health decline. Further studies are needed to elucidate the precise mechanisms by which Irisin regulates autophagy and its broader impact on physiological aging and related diseases.
    Keywords:  Drosophila; FNDC5; Iditarod; Irisin; aging; exercise
    DOI:  https://doi.org/10.3390/biom15020261
  5. Int J Mol Sci. 2025 Feb 12. pii: 1543. [Epub ahead of print]26(4):
    Oral Transfer of Anti-Aging Substances: Key Chemical Found in Reproductive Caste of Termites.
    Xin Peng, Zahid Khan, Yanan Dong, Lian-Xi Xing.
      With the rapid increase in global population aging, the incidence and mortality rates of age-related diseases are rising, becoming a worldwide issue. Therefore, researching and discovering natural compounds with anti-aging properties is crucial. Social insects such as termites exhibit significant differences in lifespan between reproductive and non-reproductive castes. Reproductive castes are exclusively fed by worker termites through trophallaxis, providing a convenient model for the discovery of natural anti-aging compounds. This thesis systematically investigates the trophallactic fluid among different caste members of termite Reticulitermes labralis. A total of 1028 metabolites were identified in the trophallactic fluid, seven of which have been validated in the KEGG database to possess anti-aging functions. This indicates that the trophallactic fluid of termites indeed contains natural compounds that promote longevity. Using the "fishing method", we successfully screened out potential life-extending compounds, including IDA (trans-3-indoleacrylic acid). Preliminary experimental results showed that IDA influences lifespan by modulating the IIS (insulin/insulin-like growth factor signaling) pathway and the RAS pathway. Notably, the modulation of the IIS pathway by IDA does not require the involvement of foxoa. Our research findings suggest that the extended lifespan of reproductive termites is diet-related and that the lifespan-extending effects of these nutritionally regulated natural compounds are conserved across different taxa.
    Keywords:  IIS pathway and RAS pathway; Reticulitermes labralis; longevity; trophallaxis compounds
    DOI:  https://doi.org/10.3390/ijms26041543
  6. Front Aging. 2025 ;6 1512322
    Klotho protects INS-1 pancreatic β-cells from senescence and enhances mitochondrial function.
    Zhihong Wang, Yunzhi Ni, Yan-Ru Lou, Gerald J Prud'homme, Qinghua Wang.
      Aging is an important contributing factor for β-cell failure which could lead to the development of type 2 diabetes (T2D). Aging β-cell exhibits signs of senescence and develops senescence-associated secretory phenotype (SASP), causing the senescence and dysfunction of neighboring cells through paracrine action. Klotho is recognized as an anti-aging gene, and the corresponding protein is α-Klotho (KL). KL exerts potent anti-aging effects on multiple cell types, but its role in β-cell aging remains unclear. Here we showed that pancreatic INS-1 cell (a rat insulinoma cell line commonly used to study pancreatic β-cell function) developed the typical hallmarks of senescent cells when treated with doxorubicin in vitro, and this was accompanied by downregulation of endogenous KL expression. Supplementation with exogenous KL protein protected pancreatic INS-1 cell against senescence, as indicated by downregulation of senescent markers and SA-β-gal staining. Notably, these effects were associated with improved mitochondrial ATP production and mitochondrial dynamic balance, as well as reduced ROS production. Our study further revealed that INS-1 cell treated with doxorubicin exhibited a reduced insulin secretion response to glucose stimulation, while supplementation with KL could reverse this effect. Our results indicate the important role of KL in regulating β-cell senescence and provide new mechanistic insights into its role in β-cell aging.
    Keywords:  Klotho; aging; cell senescence; mitochondria; β-cell
    DOI:  https://doi.org/10.3389/fragi.2025.1512322
  7. Molecules. 2025 Feb 10. pii: 816. [Epub ahead of print]30(4):
    The Anti-Aging Mechanism of Metformin: From Molecular Insights to Clinical Applications.
    Ting Zhang, Lijun Zhou, Meagan J Makarczyk, Peng Feng, Jianying Zhang.
      Aging represents a complex biological phenomenon marked by the progressive deterioration of physiological functions over time, reduced resilience, and increased vulnerability to age-related diseases, ultimately culminating in mortality. Recent research has uncovered diverse molecular mechanisms through which metformin extends its benefits beyond glycemic control, presenting it as a promising intervention against aging. This review delves into the anti-aging properties of metformin, highlighting its role in mitochondrial energy modulation, activation of the AMPK-mTOR signaling pathway, stimulation of autophagy, and mitigation of inflammation linked to cellular aging. Furthermore, we discuss its influence on epigenetic modifications that underpin genomic stability and cellular homeostasis. Metformin's potential in addressing age-associated disorders including metabolic, cardiovascular, and neurodegenerative diseases is also explored. The Targeting Aging with Metformin (TAME) trial aims to provide key evidence on its efficacy in delaying aging in humans. Despite these promising insights, significant challenges persist in gaining a more comprehensive understanding into its underlying mechanisms, determining optimal dosing strategies, and evaluating long-term safety in non-diabetic populations. Addressing these challenges is crucial to fully realizing metformin's potential as an anti-aging therapeutic.
    Keywords:  anti-aging; autophagy; clinical trials; epigenetic regulation; inflammation; metformin; mitochondrial function; nutrient sensing
    DOI:  https://doi.org/10.3390/molecules30040816
  8. Antioxidants (Basel). 2025 Feb 10. pii: 199. [Epub ahead of print]14(2):
    Antioxidant Senotherapy by Natural Compounds: A Beneficial Partner in Cancer Treatment.
    Yulia Aleksandrova, Margarita Neganova.
      Aging is a general biological process inherent in all living organisms. It is characterized by progressive cellular dysfunction. For many years, aging has been widely recognized as a highly effective mechanism for suppressing the progression of malignant neoplasms. However, in recent years, increasing evidence suggests a "double-edged" role of aging in cancer development. According to these data, aging is not only a tumor suppressor that leads to cell cycle arrest in neoplastic cells, but also a cancer promoter that ensures a chronic proinflammatory and immunosuppressive microenvironment. In this regard, in our review, we discuss recent data on the destructive role of senescent cells in the pathogenesis of cancer. We also identify for the first time correlations between the modulation of the senescence-associated secretory phenotype and the antitumor effects of naturally occurring molecules.
    Keywords:  antioxidant drugs; cellular senescence; natural products; senescence-associated secretory phenotype; senescent cells; senolytic agents; senotherapy
    DOI:  https://doi.org/10.3390/antiox14020199
  9. Biogerontology. 2025 Feb 26. 26(2): 64
    Hypoxia-inducible factor and cellular senescence in pulmonary aging and disease.
    Riya Thapa, Arockia Babu Marianesan, A Rekha, Subbulakshmi Ganesan, Mukesh Kumari, Asif Ahmad Bhat, Haider Ali, Sachin Kumar Singh, Amlan Chakraborty, Ronan MacLoughlin, Gaurav Gupta, Kamal Dua.
      Cellular senescence and hypoxia-inducible factor (HIF) signaling are crucial in pulmonary aging and age-related lung diseases such as chronic obstructive pulmonary disease idiopathic pulmonary fibrosis and lung cancer. HIF plays a pivotal role in cellular adaptation to hypoxia, regulating processes like angiogenesis, metabolism, and inflammation. Meanwhile, cellular senescence leads to irreversible cell cycle arrest, triggering the senescence-associated secretory phenotype which contributes to chronic inflammation, tissue remodeling, and fibrosis. Dysregulation of these pathways accelerates lung aging and disease progression by promoting oxidative stress, mitochondrial dysfunction, and epigenetic alterations. Recent studies indicate that HIF and senescence interact at multiple levels, where HIF can both induce and suppress senescence, depending on cellular conditions. While transient HIF activation supports tissue repair and stress resistance, chronic dysregulation exacerbates pulmonary pathologies. Furthermore, emerging evidence suggests that targeting HIF and senescence pathways could offer new therapeutic strategies to mitigate age-related lung diseases. This review explores the intricate crosstalk between these mechanisms, shedding light on how their interplay influences pulmonary aging and disease progression. Additionally, we discuss potential interventions, including senolytic therapies and HIF modulators, that could enhance lung health and longevity.
    Keywords:  Age-related lung diseases; And oxidative stress; Cellular senescence; Hypoxia-inducible factor (HIF); Inflammation; Longevity assurance genes
    DOI:  https://doi.org/10.1007/s10522-025-10208-z
  10. In Vivo. 2025 Mar-Apr;39(2):39(2): 766-777
    Secretome from HMGB1 Box A-over-expressing Adipose-derived Stem Cells Shows Potential for Skin Rejuvenation by Senescence Reversal in PM2.5-induced Senescence Cells via Stem Cell Induction.
    Zin Zin Ei, Apiwat Mutirangura, Pithi Chanvorachote.
       BACKGROUND/AIM: Exposure to particulate matter 2.5 (PM2.5) can lead to cellular senescence by generating reactive oxygen species (ROS). Box A, a DNA-binding domain found in HMGB1, is known for its ability to counteract aging characteristics. This study explored whether BoxA-induced adipose-derived stem cells secretome (BoxA-SC) can reverse senescence in DP and HWPc cells.
    MATERIALS AND METHODS: The stemness characteristics and reversal of senescence by BoxA-SC in PM2.5-induced DP and HWPc cells were assessed at the mRNA level using RT-qPCR and at the protein level using immunofluorescence analysis.
    RESULTS: BoxA-SC (1:20) treatment for 48 h induced stemness and reversed PM2.5-induced cell senescence in DP and HWPc cells. BoxA-SC significantly reduced senescence markers, including SA-β-gal staining, and decreased mRNA levels of senescence-associated secretory phenotype factors (IL1α, IL7, CXCL1) in PM2.5-induced senescent cells. DP and HWPc cells exposed to PM2.5 exhibited an increase in p21 and p16 mRNA and protein levels, which was reversed by BoxA-SC. BoxA-SC reduced p21 and p16 in DP senescent cells approximately 3- and 2-fold, respectively, compared to untreated senescent cells.
    CONCLUSION: BoxA-SC can potentially reverse cellular senescence, highlighting the therapeutic potential of stem cells in skin rejuvenation and anti-aging treatments.
    Keywords:  PM2.5; Stem cell induction; adipose; secretome; senescence reversal
    DOI:  https://doi.org/10.21873/invivo.13881
  11. iScience. 2025 Feb 21. 28(2): 111854
    UFMylation maintains YAP stability to promote vascular endothelial cell senescence.
    Yanan Liu, Min Zuo, Aiwei Wu, Zhaoxiang Wang, Siting Wang, Yongping Bai, Junzhi Zhou, Hu Wang.
      Endothelial cell (EC) senescence is an accomplice for vascular aging, which leads to cardiovascular diseases (CVDs). Evidences showed that Hippo-Yes-associated protein (YAP) signaling pathway plays an essential role in aging-associated CVDs. Here, we reported that YAP was elevated in senescent human umbilical vein endothelial cells (HUVECs) and inhibition of YAP could attenuate HUVECs senescence. Besides, our findings revealed that the activity of UFMylation and the level of YAP were both elevated in senescent cells. Furthermore, UFM1-modified YAP was upregulated in senescent ECs, and increased the stability of YAP. Importantly, we found that compound 8.5, an inhibitor of E1 of UFMylation, can alleviate vascular aging in aged mice. Together, our finding provides molecular mechanism by which UFMylation maintains YAP stability and exerts an important role in promoting cell senescence, and identified that a previously unrecognized UFMylation is a potential therapeutic target for anti-aging.
    Keywords:  Biochemistry; Biological sciences; Cell; Cell biology
    DOI:  https://doi.org/10.1016/j.isci.2025.111854
  12. Mol Ther. 2025 Feb 22. pii: S1525-0016(25)00120-0. [Epub ahead of print]
    Long-term effects of s-KL treatment in wild-type mice: enhancing longevity, physical well-being, and neurological resilience.
    Joan Roig-Soriano, Ángel Edo, Sergi Verdés, Carlos Martín-Alonso, Cristina Sánchez-de-Diego, Laura Rodriguez-Estevez, Antonio L Serrano, Carmela R Abraham, Assumpció Bosch, Francesc Ventura, Bryen A Jordan, Pura Muñoz-Cánoves, Miguel Chillón.
      Aging is a major risk factors for pathologies including sarcopenia, osteoporosis, and cognitive decline, which bring suffering, disability, and elevated economic and social costs. Therefore, new therapies are needed to achieve healthy aging. The protein Klotho (KL) has emerged as a promising anti-aging molecule due to its pleiotropic actions modulating insulin/IGF-1 and Wnt signaling pathways and reducing inflammatory and oxidative stress. Here, we explored the anti-aging potential of the secreted isoform of this protein on the non-pathological aging progression of wild-type mice. The delivery of an AAV9 coding for s-KL efficiently increased the concentration of s-KL in serum, resulting in a 20% increase in lifespan. Notably, KL treatment improved physical fitness, related to a reduction in muscle fibrosis and an increase in muscular regenerative capacity. KL treatment also improved bone microstructural parameters associated with osteoporosis. Finally, s-KL-treated mice exhibited increased cellular markers of adult neurogenesis and immune response, with transcriptomic analysis revealing induced phagocytosis and immune cell activity in the aged hippocampus. These results show the potential of elevating s-KL expression to simultaneously reduce the age-associated degeneration in multiple organs, increasing both life and health span.
    DOI:  https://doi.org/10.1016/j.ymthe.2025.02.030
  13. Cell Mol Life Sci. 2025 Feb 22. 82(1): 83
    37 kDa LRP::FLAG enhances telomerase activity and reduces ageing markers in vivo.
    Tyrone C Otgaar, Martin Bernert, Gavin Morris, Pavan Baichan, Monique J Bignoux, Boitelo Letsolo, Stefan F T Weiss, Eloise Ferreira.
      Ageing is a degenerative process characterised by a decline in physiological functioning of the organism. One of the core regulators of cellular ageing are telomeres, repetitive DNA sequences of TTAGGG that cap the ends of chromosomes and are maintained by the ribonucleoprotein complex, telomerase. Age-dependent progressive loss of the telomere ends eventually induces cell cycle arrest for the induction of either replicative senescence or apoptosis. It was previously established that overexpression of the 37 kDa/ 67 kDa laminin receptor (LRP/LR) increased telomerase activity and telomere length while concomitantly reducing senescence markers in aged normal cells in vitro. Therefore, it was hypothesized that elevating LRP/LR in vivo may increase telomerase activity and hinder the ageing process on an organism scale. To this end, aged C57BL/6J mice were treated/transfected to induce an overexpression of LRP::FLAG. Various physiological tests and histological analyses were performed to assess overall organism fitness as well as to discern the treatments' ability at reducing tissue degeneration and atrophy. It was found that mice overexpressing LRP::FLAG displayed improved physiological characteristics and markedly less tissue degeneration and atrophy when compared to control and non-treated mice. Alongside these improvements, certain organs displayed increased telomerase activity with a corresponding elongation in average telomere length. In addition the overexpression of LRP::FLAG significantly improved various proliferative and anti-ageing associated proteins while causing a concomitant decrease in senescence associated proteins. These findings are therefore indicative of a novel function of LRP/LR delaying the onset of senescence, while also promoting healthier ageing through elevating TERT and telomerase activity.
    Keywords:  Ageing; C57BL/6J mice; LRP; Mitochondrial dysfunction; Senescence; Telomerase
    DOI:  https://doi.org/10.1007/s00018-025-05593-0
  14. Sci Rep. 2025 Feb 23. 15(1): 6525
    Lysine-specific demethylase 1 (LSD1) suppresses cellular senescence by riboflavin uptake-dependent demethylation activity.
    Taiichi Osumi, Taiki Nagano, Tetsushi Iwasaki, Jotaro Nakanishi, Kazuyuki Miyazawa, Shinji Kamada.
      Cellular senescence is defined as a permanent proliferation arrest caused by various stresses, including DNA damage. We have recently identified the riboflavin transporter SLC52A1, whose expression is increased in response to senescence-inducing stimuli. Interestingly, increased expression of SLC52A1 suppresses cellular senescence through the uptake of riboflavin and an increase in intracellular flavin adenine dinucleotide (FAD), an enzyme cofactor synthesized from riboflavin. However, how FAD suppresses cellular senescence has not been fully elucidated. Therefore, in this study, we focused on lysine-specific demethylase 1 (LSD1), which uses FAD as a cofactor. First, we found that LSD1 inhibition promoted DNA damage-induced cellular senescence, whereas ectopic expression of LSD1 suppressed cellular senescence, suggesting that LSD1 suppresses senescence. In addition, the demethylation activity of LSD1 against histone H3 and p53 was increased by senescence-inducing stress in a riboflavin uptake-dependent manner. Furthermore, it was revealed that the LSD1 demethylation activity was required for suppression of pro-senescence genes Sirtuin-4 and p21 whose expression is modified by methylation status of histone H3 and possibly p53, respectively. Collectively, these results suggest that the FAD increase by senescence-inducing stress leads to LSD1-mediated demethylation of histone H3 and p53, which results in the suppression of pro-senescence genes to inhibit senescence induction.
    Keywords:  Cellular senescence; DNA damage; Demethylation; Flavin adenine dinucleotide (FAD); LSD1; Riboflavin
    DOI:  https://doi.org/10.1038/s41598-025-91004-0
  15. Aging Cell. 2025 Feb 23. e70021
    Circular RNA Telomerase Reverses Endothelial Senescence in Progeria.
    Weifeng Qin, Kathrina D Castillo, Hongye Li, Thi Kim Cuc Nguyen, Daniel L Kiss, John P Cooke, Anahita Mojiri.
      Telomeres shorten with each cell division, acting as a chronometer of cell age. The enzyme telomerase, primarily active in stem cells, reverses telomere erosion. We have previously observed that transient transfection with human TERT mRNA extends telomeres and mitigates hallmarks of senescence in replicatively aged human cells or those affected by Hutchinson-Gilford progeroid syndrome (HGPS). However, due to its short half-life, mRNA requires frequent administration. In this study, we hypothesized that TERT circular (circ) RNA would extend the duration of telomerase expression and be more effective at reversing hallmarks of senescence in endothelial cells derived from HGPS patients. We observe that a single transfection of TERT circRNA is more effective than mRNA in the extension of telomere length, as determined by quantitative fluorescence in situ hybridization. Furthermore, TERT circRNA reduced the number of β-gal positive cells by three-fold and normalized nuclear morphology in HGPS endothelial cells (HGPS-ECs). Moreover, TERT circRNA substantially reduced senescent markers, inflammatory markers, and DNA damage markers, including Progerin, p16, p21, IL-1B, IL-6, IL-8, MCP1, and γH2AX. Additionally, it restored NO production, enhanced cell proliferation, promoted angiogenesis, improved LDL uptake, reduced mitochondrial ROS, and normalized mitochondrial membrane potential more effectively. Our data suggest that TERT circRNA is superior to linear TERT mRNA in reversing processes involved in senescence.
    Keywords:  RNA therapy; aging; endothelial cells; senescence; telomerase
    DOI:  https://doi.org/10.1111/acel.70021
  16. Curr Issues Mol Biol. 2025 Feb 18. pii: 130. [Epub ahead of print]47(2):
    Ganodermalucidum Extract Modulates Gene Expression Profiles Associated with Antioxidant Defense, Cytoprotection, and Senescence in Human Dermal Fibroblasts: Investigation of Quantitative Gene Expression by qPCR.
    Harald Kühnel, Markus Seiler, Barbara Feldhofer, Atefeh Ebrahimian, Michael Maurer.
      Cellular senescence plays a crucial role in skin aging, with senescent dermal fibroblasts contributing to reduced skin elasticity and increased inflammation. This study investigated the potential of Ganoderma lucidum (Reishi) ethanol extract to modulate the senescent phenotype of human dermal fibroblasts. Reishi powder of two different vendors was used. The extract was produced by extracting the Reishi powder for at least three weeks in 40% ethanol at room temperature. Etoposide-induced senescent fibroblasts were treated with Reishi extracts from two commercial sources for 14 days. Gene expression analysis was performed using qPCR to assess senescence makers, antioxidant defense, and extracellular matrix remodeling. Results showed that Reishi extracts significantly upregulated antioxidant and cytoprotective genes, including Heme oxygenase 1 (HO-1), γ-Glutamylcysteine synthetase (γGCS-L), and NAD(P)H dehydrogenase [quinone] 1 (NQO1), compared to untreated controls. Importantly, Reishi treatment suppressed the expression of p16INK4a, a key marker of cellular senescence, while transiently upregulating p21Cip1. The extracts also demonstrated potential senolytic properties, reducing the percentage of senescent cells as measured by senescence-associated β-galactosidase staining. However, Reishi treatment did not mitigate the upregulation of MMP1 and IL-8 in one Reishi treatment group, indicating differences in the preparations of different vendors. These findings suggest that Ganoderma lucidum extract may help alleviate some aspects of cellular senescence in dermal fibroblasts, primarily through enhanced antioxidant defense and cytoprotection, potentially offering a novel approach to combat skin aging.
    Keywords:  Ganoderma lucidum; cellular senescence; etoposide; human dermal fibroblast; senolytic; senomorphic
    DOI:  https://doi.org/10.3390/cimb47020130
  17. Antioxidants (Basel). 2025 Jan 27. pii: 147. [Epub ahead of print]14(2):
    Effects of Silibinin on Delaying Aging in Drosophila melanogaster.
    Kai Zhu, Hang Ni, Eqra Hafeez, Yaxuan Hu, Fan Hu, Dongsheng Du, Dongsheng Chen.
      Aging is an inevitable physiological process, but delaying aging has always been an enduring human pursuit. Silibinin (SIL), derived from the seeds of the milk thistle plant, exhibits a broad spectrum of pharmacological properties, including anti-tumor effects, liver protection, inhibition of apoptosis, and alleviation of inflammation. However, whether it has anti-aging effects remains unclear. The SIL dietary supplement to Drosophila melanogaster prolonged lifespan, improved climbing ability, ameliorated age-associated intestinal barrier disruption, enhanced the resistance to oxidative stress, and increased the enzyme activities of superoxide dismutase (SOD) and catalase (CAT). Furthermore, RNA-seq results showed that SIL addition significantly upregulated 74 genes and downregulated 50 genes compared with the control. KEGG (Kyoto Encyclopedia of genes and genomes) analysis demonstrated that these differentially expressed genes were primarily involved in the Toll signaling pathway and endoplasmic reticulum proteins processing, six among which, including IM2, IM3, Drsl3, CG7556, GCS1, and TRAM, were particularly involved in the regulation by SIL supplementation. The results indicate that SIL exhibits anti-aging effects by enhancing antioxidant capacity and regulating aging-related signaling pathways. Therefore, SIL shows a potential application in anti-aging dietary regimens.
    Keywords:  Drosophila melanogaster; aging; lifespan; silibinin
    DOI:  https://doi.org/10.3390/antiox14020147
  18. Pharmaceuticals (Basel). 2025 Feb 12. pii: 244. [Epub ahead of print]18(2):
    Cellular Senescence in Health, Disease, and Lens Aging.
    Ying Qin, Haoxin Liu, Hongli Wu.
      Background: Cellular senescence is a state of irreversible cell cycle arrest that serves as a critical regulator of tissue homeostasis, aging, and disease. While transient senescence contributes to development, wound healing, and tumor suppression, chronic senescence drives inflammation, tissue dysfunction, and age-related pathologies, including cataracts. Lens epithelial cells (LECs), essential for maintaining lens transparency, are particularly vulnerable to oxidative stress-induced senescence, which accelerates lens aging and cataract formation. This review examines the dual role of senescence in LEC function and its implications for age-related cataractogenesis, alongside emerging senotherapeutic interventions. Methods: This review synthesizes findings on the molecular mechanisms of senescence, focusing on oxidative stress, mitochondrial dysfunction, and the senescence-associated secretory phenotype (SASP). It explores evidence linking LEC senescence to cataract formation, highlighting key studies on stress responses, DNA damage, and antioxidant defense. Recent advances in senotherapeutics, including senolytics and senomorphics, are analyzed for their potential to mitigate LEC senescence and delay cataract progression. Conclusions: LEC senescence is driven by oxidative damage, mitochondrial dysfunction, and impaired redox homeostasis. These factors activate senescence path-ways, including p53/p21 and p16/Rb, resulting in cell cycle arrest and SASP-mediated inflammation. The accumulation of senescent LECs reduces regenerative capacity, disrupts lens homeostasis, and contributes to cataractogenesis. Emerging senotherapeutics, such as dasatinib, quercetin, and metformin, show promise in reducing the senescent cell burden and modulating the SASP to preserve lens transparency.
    Keywords:  cataractogenesis; cellular senescence; lens epithelial cells; oxidative stress; senescence-associated secretory phenotype; senotherapeutics
    DOI:  https://doi.org/10.3390/ph18020244
  19. Exp Cell Res. 2025 Feb 21. pii: S0014-4827(25)00046-1. [Epub ahead of print] 114450
    Human umbilical cord mesenchymal stem cell-derived exosome ameliorate doxorubicin-induced senescence.
    Zhen Yang, Feng Yan, Jiangwei Yuan, Manjun Yang, Jinyu Wang, Changqiao You, Kaiqun Ren.
       BACKGROUND: Cellular senescence refers to a condition where cells permanently cease division while maintaining metabolic activity. Doxorubicin (Dox) is known as an agent of induction of cellular senescence. This study aimed to explore the potential role of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) in mitigating Dox induced senescent.
    METHOD: NIH3T3 cells were treated by various concentrations of Dox with or without hucMSC-Exo, cell morphology, viability, migration, senescence-associated SA-β-Gal staining were monitored. Cellular senescence was induced in C57BL/6J mice via administration of 5 mg/kg Doxorubicin, followed by treatment with hucMSC-Exo or metformin. Assessments included body weight, liver and kidney weight, colon length, SA-β-Gal staining of kidney and skin, molecular biomarkers of aging such as p16INK4A, p53, and p21Waf1/Clip1 to evaluate senescence status.
    RESULT: We found that after the treatment of exosomes or metformin improved several aging-related phenotypes in both mouse and cellular models, including increases in body weight, liver and kidney weights, and the reduction of SA-β-Gal positive cells in kidney and skin tissues as well as cell models. At the molecular level, hucMSC-Exo resulted in the downregulation of inflammatory factors and senescence markers in liver and kidney tissues as well as cell models.
    CONCLUSION: Our study demonstrates hucMSC-Exo may ameliorate Dox induced senescence either in NIH3T3 cells or in mice.
    Keywords:  Doxorubicin; HucMSC-Exo; Inflammation; Senescence
    DOI:  https://doi.org/10.1016/j.yexcr.2025.114450
  20. Endocr Rev. 2025 Feb 25. pii: bnae034. [Epub ahead of print]
    Endocrine Controls of Skin Aging.
    Markus Böhm, Agatha Stegemann, Ralf Paus, Konrad Kleszczyński, Pallab Maity, Meinhard Wlaschek, Karin Scharffetter-Kochanek.
      Skin is the largest organ of the human body and undergoes both intrinsic (chronological) and extrinsic aging. While intrinsic skin aging is driven by genetic and epigenetic factors, extrinsic aging is mediated by external threats such as UV irradiation or fine particular matters, the sum of which is referred to as exposome. The clinical manifestations and biochemical changes are different between intrinsic and extrinsic skin aging, albeit overlapping features exist, eg, increased generation of reactive oxygen species, extracellular matrix degradation, telomere shortening, increased lipid peroxidation, or DNA damage. As skin is a prominent target for many hormones, the molecular and biochemical processes underlying intrinsic and extrinsic skin aging are under tight control of classical neuroendocrine axes. However, skin is also an endocrine organ itself, including the hair follicle, a fully functional neuroendocrine "miniorgan." Here we review pivotal hormones controlling human skin aging focusing on IGF-1, a key fibroblast-derived orchestrator of skin aging, of GH, estrogens, retinoids, and melatonin. The emerging roles of additional endocrine players, ie, α-melanocyte-stimulating hormone, a central player of the hypothalamic-pituitary-adrenal axis; members of the hypothalamic-pituitary-thyroid axis; oxytocin, endocannabinoids, and peroxisome proliferator-activated receptor modulators, are also reviewed. Until now, only a limited number of these hormones, mainly topical retinoids and estrogens, have found their way into clinical practice as anti-skin aging compounds. Further research into the biological properties of endocrine players or its derivatives may offer the development of novel senotherapeutics for the treatment and prevention of skin aging.
    Keywords:  endocrinology; hormones; photoaging; senescence
    DOI:  https://doi.org/10.1210/endrev/bnae034
  21. Biogerontology. 2025 Feb 26. 26(2): 63
    The role of different physical exercises as an anti-aging factor in different stem cells.
    Jia Xu, Zhe Song.
      The senescence process is connected to the characteristics of cellular aging. Understanding their causal network helps develop a framework for creating new treatments to slow down the senescence process. A growing body of research indicates that aging may adversely affect stem cells (SCs). SCs change their capability to differentiate into different cell types and decrease their potential for renewal as they age. Research has indicated that consistent physical exercise offers several health advantages, including a reduced risk of age-associated ailments like tumors, heart disease, diabetes, and neurological disorders. Exercise is a potent physiological stressor linked to higher red blood cell counts and an enhanced immune system, promoting disease resistance. Sports impact mesenchymal SCs (MSCs), hematopoietic SCs (HSCs), neuronal SCs (NuSCs), and muscular SCs (MuSCs), among other aged SCs types. These changes to the niche will probably affect the amount and capability of adult SCs after exercise. In this work, we looked into how different types of SCs age. The impact of physical activity on the aging process has been studied. Additionally, there has been discussion and study on the impact of different sports and physical activities on SCs as an anti-aging component.
    Keywords:  Aging; Hematopoietic stem cells; Hormesis; Mesenchymal stem cells; Muscular stem cells; Physical exercises; Stem cell
    DOI:  https://doi.org/10.1007/s10522-025-10205-2
  22. Biomolecules. 2025 Jan 28. pii: 187. [Epub ahead of print]15(2):
    Perception and Longevity Control in Invertebrate Model Organisms-A Mini-Review of Recent Advances.
    Nicholas Pontillo, Yang Lyu.
      Perception alone can, in some cases, be sufficient to modulate aging and longevity. These influences on aging are perhaps mediated by changes in motivational states that regulate metabolism and physiology to impact health. Simple invertebrate models uniquely enable detailed dissection of integrative pathways linking perceptions to aging and remain the leading systems for advancing this field. Over the past 25 years, studies using the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans have demonstrated that sensory cues, such as those related to food or mating, can influence aging independently of the physical acts associated with them. In this review, we highlight recent advancements in these invertebrate models, focusing on two key areas of progress: (i) the discovery of lifespan modulation driven by novel sensory cues across multiple modalities, including non-sexual social experience, light, and dietary choices; and (ii) the assignment of new aging-regulation functions to specific neurons downstream of sensory perception. The latter offers an exciting first glimpse at the neuronal circuits integrating sensory cues, motivational states, physiology, and aging.
    Keywords:  Caenorhabditis elegans; Drosophila melanogaster; life history theory; lifespan; longevity; perception
    DOI:  https://doi.org/10.3390/biom15020187
  23. Actas Dermosifiliogr. 2025 Feb 20. pii: S0001-7310(25)00100-0. [Epub ahead of print]
    POLLUTION, A RELEVANT EXPOSOME FACTOR IN SKIN AGING AND THE ROLE OF MULTI-BENEFIT PHOTOPROTECTION.
    J Santamaria, Y Gilaberte, L Prudkin, J Piquero-Casals.
      Skin aging is a complex, continuous, multifactorial process resulting from cumulative morphological and functional changes in the skin over time.This happens because of 2 processes: intrinsic and extrinsic skin aging. Intrinsic skin aging occurs naturally over time and reflects each person's genetic makeup, or heredity. Extrinsic skin aging, on the other hand, is due to exposomal factors, such as solar radiation, air pollution, tobacco or nutrition, being the first 2 the most important of all. Exposure to air pollutants, primarily gases such as ground-level ozone and particulate matter, can accelerate the process via 4 key mechanisms: reactive oxygen species generation, inflammation, skin microbiome disruption, and aryl hydrocarbon receptor activation. Regarding solar radiation, all wavelengths reaching the Earth's surface have an impact on the skin, having a synergistic effect with air pollution ("photo-pollution"). Here, we discuss this phenomenon and mitigation strategies, including sunscreens, cosmetics with film-forming plus antioxidant ingredients, and oral supplementation.
    Keywords:  Envejecimiento de la piel; Skin aging; air pollution; anti-pollution; anticontaminación; contaminación del aire; exposoma; exposome; radiación solar; solar radiation
    DOI:  https://doi.org/10.1016/j.ad.2024.11.025
  24. Pharmaceuticals (Basel). 2025 Feb 12. pii: 246. [Epub ahead of print]18(2):
    Anti-Aging Potential of Avocado Oil via Its Antioxidant Effects.
    Olin Torres-Isidro, Marcela González-Montoya, Manuel Alejandro Vargas-Vargas, Ulises Florian-Rodriguez, Claudia Isabel García-Berumen, Rocío Montoya-Pérez, Alfredo Saavedra-Molina, Elizabeth Calderón-Cortés, Alain Raimundo Rodríguez-Orozco, Christian Cortés-Rojo.
      Aging is a process characterized by tissue degeneration, increased susceptibility to chronic degenerative diseases, infections, and the appearance of neoplasms, which leads to disability and a reduction in the length and quality of life. This phenomenon is the result of the convergence of multiple processes, including mitochondrial dysfunction, fibrosis, inflammation, dysregulation of cell death processes, and immunosenescence. These processes have as their point of convergence an increase in the production of ROS. Avocado oil (Persea americana Mill.) contains a diverse array of bioactive compounds, including oleic acid, phytosterols, chlorophylls, xanthones, xanthines, and carotenoids. These bioactive compounds have the capacity to modulate the excessive production of ROS, thereby reducing the progression of age-related diseases and extending lifespan in experimental models of aging. In addition, several studies have demonstrated the efficacy of avocado oil in mitigating age-related diseases, including hypertension; insulin resistance; diabetes; non-alcoholic liver disease; and degenerative processes such as hearing loss, cognitive decline, neurodegeneration, and impaired wound healing. In light of these findings, it is hypothesized that avocado oil is a promising agent capable of promoting healthspan in later stages of life owing to its direct antioxidant actions and the activation of pathways that enhance endogenous antioxidant levels.
    Keywords:  Persea americana; aging; healthspan; inflammation; lifespan; mitochondria; oleic acid; oxidative stress; phytosterols; senescence
    DOI:  https://doi.org/10.3390/ph18020246
  25. Antioxidants (Basel). 2025 Feb 03. pii: 177. [Epub ahead of print]14(2):
    The Role of Extracellular Vesicles in Aging and Age-Related Disorders.
    Bharathi Hassan Ganesh, Himabindu Padinjarathil, Ramya Lakshmi Rajendran, Prasanna Ramani, Prakash Gangadaran, Byeong-Cheol Ahn.
      A variety of molecular and cellular changes distinguish the multifaceted biological process of aging. Recent studies in this decade have demonstrated the essential role of extracellular vesicles (EVs) in the aging process. Mitochondrial malfunction and increased oxidative stress are major contributors for the aging process. This review investigates the role of EVs in intercellular communication, tissue regeneration, and inflammation in the context of aging. We also discuss the exosome and its utility to reduce oxidative stress, which is a key part of aging, as well as the possibility of using the exosomes (EVs) as anti-aging drugs. Changes in cargo composition can influence the aging phenotype and impact the functionality of cells and tissues. Additionally, the role of EVs in oxidative stress during the aging process addresses potential treatment strategies and the development of biomarkers for age-associated disorders. The review also highlighted the role of exosomes in providing antioxidant properties, which help reduce excessive reactive oxygen species (ROS) and strengthen cellular defenses against oxidative stress. Additionally, it emphasized the role of extracellular vesicles (EVs) in age-related pathologies, such as neurodegenerative diseases, cardiovascular disorders, and immunosenescence, offering insights into targeted interventions for promoting healthy aging. This article provides a comprehensive analysis of the current body of knowledge regarding the therapeutic effects of EVs on aging, with a particular emphasis on the implications of this emerging field of research and its relationship to oxidative stress.
    Keywords:  age-related diseases; cargo composition; extracellular vesicles; intercellular communication; therapeutic strategies
    DOI:  https://doi.org/10.3390/antiox14020177
  26. Curr Issues Mol Biol. 2025 Jan 29. pii: 87. [Epub ahead of print]47(2):
    Anthocyanin-Binding Affinity and Non-Covalent Interactions with IIS-Pathway-Related Protein Through Molecular Docking.
    Haroon, Zahid Khan, Wasim Javaid, Lian-Xi Xing.
      Anthocyanins compounds, including cyanidin, malvidin, pelargonidin, peonidin, and petunidin, have demonstrated remarkable anti-aging and insulin-sensitizing properties through their interactions with proteins associated with the insulin/insulin-like growth factor signaling (IIS) pathway in Reticulitermes chinensis, employing advanced molecular docking techniques to elucidate strong binding affinities between specific anthocyanins and key proteins such as Pdk1, EIF4E, and Tsc2 in R. chinensis, suggesting a potential mechanism for their anti-aging effects. These findings not only provide critical insights into the therapeutic potential of anthocyanins for mitigating insulin resistance and promoting longevity, but also highlight the efficacy of in silico molecular docking as a predictive tool for small-molecule-protein interactions. Our research opens new avenues for the development of innovative therapeutic strategies targeting age-related diseases. However, further investigations, including a comprehensive chromosomal analysis and in vivo studies, are essential in order to fully elucidate the molecular mechanism underlying these interactions and their physiological implications. The detailed characterization of anthocyanin-binding affinities and their interactions with key regulatory genes presents exciting opportunities for advancement in molecular medicine, pharmacology, and the development of novel nutraceuticals.
    Keywords:  aging; in silico analysis; insulin signaling pathway; polyphenols
    DOI:  https://doi.org/10.3390/cimb47020087
  27. Biomolecules. 2025 Feb 17. pii: 296. [Epub ahead of print]15(2):
    Improvement of Skin Condition Through RXR Alpha-Activating Materials.
    Sanghyun Ye, Seonju Lee, Seongsu Kang, Seung-Hyun Jun, Nae-Gyu Kang.
      Retinol is well-known anti-aging material in the cosmetics industry, owing to its proven superior efficacy both in vitro and in vivo. Despite its high efficacy, retinol is associated with limitations, such as skin irritation and its potential photodegradation. Retinol is converted into retinoid acid within cells, which then exerts a cellular response by activating both the retinoic acid receptor (RAR) and retinoid x receptor (RXR). Noting that RAR activity is associated with skin irritation and RXR activation alone can enhance skin-related indicators without inducing inflammation, we developed an alternative approach for skin anti-aging focusing solely on RXR activation. We found that combined treatment of andrographolide and Bidens pilosa extract successfully activated RXR alpha and enhanced RXRA gene expression. Moreover, we investigated their efficacy using dermal fibroblasts and keratinocytes and found that they enhanced the gene expression of extracellular matrix (ECM) proteins with anti-oxidant and anti-inflammation efficacies. Finally, in a human clinical trial, we confirmed that our materials successfully improved wrinkles in various areas, skin elasticity and hydration without causing irritating side effects. These findings highlight the potential of our RXR alpha-activating materials as an anti-wrinkle solution that avoids the typical side effects associated with retinol.
    Keywords:  RXR; anti-inflammation; anti-oxidant; skin aging; wrinkle improvement
    DOI:  https://doi.org/10.3390/biom15020296
  28. Front Med. 2025 Feb 27.
    Update of cellular senescence in kidney fibrosis: from mechanism to potential interventions.
    Lina Yang, Liang Ma, Ping Fu, Jing Nie.
      Kidney fibrosis is the final common pathway of virtually all chronic kidney disease (CKD). However, despite great progress in recent years, no targeted antifibrotic therapies have been approved. Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of CKD. Senescent renal tubular cells, fibroblasts, endothelial cells, and podocytes have been detected in the kidneys of patients with CKD and animal models. Nonetheless, although accumulated evidence supports the essential role of cellular senescence in CKD, the mechanisms that promote cell senescence and how senescent cells contribute to CKD remain largely unknown. In this review, we summarize the features of the cellular senescence of the kidney and discuss the possible functions of senescent cells in the pathogenesis of kidney fibrosis. We also address whether pharmacological approaches targeting senescent cells can be used to retard the the progression of kidney fibrosis.
    Keywords:  SASP; cell cycle arrest; cellular senescence; kidney fibrosis; senolytics; senomorphics
    DOI:  https://doi.org/10.1007/s11684-024-1117-z
  29. Trends Endocrinol Metab. 2025 Feb 24. pii: S1043-2760(25)00018-9. [Epub ahead of print]
    Hallmarks of ovarian aging.
    Chuqing Wu, Dan Chen, Michael B Stout, Meng Wu, Shixuan Wang.
      Ovarian aging is considered to be the pacemaker of female aging, and is linked to various comorbidities such as osteoporosis, cardiovascular diseases, and cognitive decline. Many efforts have been made to determine the mechanisms underlying ovarian aging, but their potential to act as hallmarks to predict and intervene in this process currently remains unclear. In this review we propose nine hallmarks as common features of ovarian aging: genomic instability, telomere attrition, epigenetic alterations, impaired autophagy, cellular senescence, deregulated nutrient-sensing, mitochondrial dysfunction, oxidative stress, and chronic inflammation. Understanding the interaction between these hallmarks poses a significant challenge but may also pave the way to the identification of pharmaceutical targets that can attenuate ovarian aging.
    Keywords:  endocrine; fertility; hallmarks; oocyte; ovarian aging
    DOI:  https://doi.org/10.1016/j.tem.2025.01.005
  30. Medicina (Kaunas). 2025 Jan 24. pii: 207. [Epub ahead of print]61(2):
    Exploring Anti-Aging Effects of Topical Treatments for Actinic Keratosis.
    Federica Li Pomi, Andrea d'Aloja, Dario Valguarnera, Mario Vaccaro, Francesco Borgia.
      Background and Objectives: Actinic keratosis (AK) is a precancerous cutaneous lesion driven by chronic ultraviolet (UV) exposure, often coexisting with features of photoaging, such as wrinkles and pigmentary irregularities. Recent evidence suggests that treatments for AK may also counteract photoaging through shared molecular pathways, including oxidative stress and inflammation. This narrative review explores the dual benefits of AK therapies, highlighting their potential anti-aging and skin-lightening effects, and implications for improving skin appearance alongside lesion clearance. Materials and Methods: The literature was analyzed to assess the efficacy, mechanisms, and cosmetic outcomes of commonly used AK treatments, including topical agents (5-fluorouracil (5-FU), imiquimod, diclofenac, and tirbanibulin), and photodynamic therapy (PDT). Studies highlighting their effects on photoaged skin, collagen remodeling, pigmentation, and patient satisfaction were reviewed. Results: PDT emerged as the most validated treatment, demonstrating improved collagen synthesis, skin texture, and pigmentation. 5-FU showed remodeling of the dermal matrix and increased procollagen levels, but local skin reactions represent a major limitation. Imiquimod enhanced dermal fibroplasia and reduced solar elastosis, while diclofenac provided mild photodamage improvements with minimal adverse effects. Tirbanibulin showed promising aesthetic outcomes, including skin lightening and a reduction in mottled pigmentation, with favorable tolerability. Conclusions: AK therapies offer a dual-purpose strategy, addressing both precancerous lesions and cosmetic concerns associated with photoaging. While PDT remains the gold standard, emerging agents like tirbanibulin ointment exhibit substantial potential. Future research should focus on optimizing treatment protocols and evaluating long-term cosmetic outcomes to enhance patient satisfaction and compliance.
    Keywords:  5-fluorouracil; actinic keratosis; anti-aging; oxidative stress; photodynamic therapy; skin aging; skin lightening; solar lentigo; tirbanibulin
    DOI:  https://doi.org/10.3390/medicina61020207
  31. Nutrients. 2025 Feb 18. pii: 722. [Epub ahead of print]17(4):
    The Power of Environment: A Comprehensive Review of the Exposome's Role in Healthy Aging, Longevity, and Preventive Medicine-Lessons from Blue Zones and Cilento.
    Silvana Mirella Aliberti, Mario Capunzo.
      Aging and longevity are shaped by the exposome, a dynamic network of environmental, social, and biological factors. Understanding how these exposures interact with biological mechanisms can inform strategies for healthier aging. Background/Objectives: This review explores the exposome as a dynamic system encompassing both protective and risk factors, with a specific focus on how beneficial environmental exposures, microbiome diversity, lifestyle behaviors, and resilience mechanisms contribute to successful aging. By analyzing high-longevity populations, such as the Blue Zones and Cilento, it aims to identify common determinants of successful aging. Methods: A mixed-method study was conducted, combining a systematic review of the English literature (2003-2024) with a comparative analysis of longevity regions. A structured search was performed in PubMed, Scopus, and Google Scholar using keywords such as "longevity", "Blue Zones", "Cilento", "microbiome", "environmental factors", and related terms. Additionally, qualitative and quantitative analysis were applied to assess key protective factors across different aging models. Results: This study identified key factors contributing to successful aging in longevity hotspots, including sustained exposure to biodiverse natural environments, adherence to Mediterranean or plant-based diet rich in polyphenols and probiotics, regular physical activity, strong social networks, and psychological resilience. A novel aspect of this review is the role of the gut microbiome as a mediator between environmental exposures and immune-metabolic health, influencing inflammation modulation and cellular aging. Despite geographic and cultural differences, case studies reveal a shared pattern of protective factors that collectively enhance lifespan and healthspan. Conclusions: The exposome is a critical determinant of aging trajectories, acting through complex interactions between environmental and biological mechanisms. By integrating insights from high-longevity populations, this mixed-method study proposes a comprehensive framework for optimizing microbiome health, enhancing resilience, and promoting protective environmental exposures. These findings provide a translational perspective to guide future interventions in aging research and global health initiatives.
    Keywords:  Blue Zones; Cilento; aging; environment; exposome; health and disease; longevity; preventive medicine; protective factors; risk factors
    DOI:  https://doi.org/10.3390/nu17040722
  32. Ther Deliv. 2025 Feb 28. 1-15
    Effective release of Eryngium maritimum L. callus extract via encapsulation in multilayered liposomes for skin delivery.
    Euihyun Kim, Jihyeon Jang, Myeong-Jin Lim, Soo-Yun Kim, Seon Kyu Yun, Jihyeok Song, Hyo Hyun Seo, Jeong Hun Lee, Sang Hyun Moh.
       AIMS: This study aimed to evaluate the potential of Eryngium maritimum L. (EM) callus media filtrate (ECMF) for enhanced skin delivery through multilayered liposomes (MLs).
    MATERIALS & METHODS: ECMF was applied to human skin cells to assess its antioxidant, anti-inflammatory, and skin barrier-enhancing properties. ECMF was encapsulated in MLs to enhance delivery efficiency, creating a formulation called Cellbiome. Clinical trials involving human participants were conducted to compare its effects with traditional formulations, assessing parameters such as skin density, hydration, elasticity, and wrinkle reduction.
    RESULTS: Cellbiome significantly improved skin density and moisturization, outperforming conventional formulations. ML encapsulation facilitated deeper penetration of active ingredients beyond the stratum corneum, leading to synchronized improvements in multiple skin parameters, including elasticity, wrinkle reduction, and overall skin health. Transcriptomic and metabolomic analyses further confirmed ECMF's bioactivity and its role in skin improvement.
    CONCLUSIONS: ML-based formulations, such as Cellbiome, offer superior efficacy in skincare applications compared to conventional methods. This study underscores the importance of advanced delivery technologies in cosmetics and highlights the need for further research to optimize the benefits of natural extracts like EM for human skin, potentially advancing dermatological and cosmeceutical applications.
    Keywords:  Eryngium maritimum L.; callus extract; liposome; moisturization; skin; skin barrier
    DOI:  https://doi.org/10.1080/20415990.2025.2470614
  33. Int J Mol Sci. 2025 Feb 16. pii: 1693. [Epub ahead of print]26(4):
    The Potential of Superoxide Dismutase-Rich Tetraselmis chuii as a Promoter of Cellular Health.
    Stuart P Cocksedge, Lalia Mantecón, Enrique Castaño, Carlos Infante, Stephen J Bailey.
      Tetraselmis chuii (T. chuii) is a green, marine, eukaryotic, microalgae that was authorized in the European Union (EU) as a novel food for human consumption in 2014, and as a food supplement in 2017. This narrative review will provide an overview of preclinical and clinical trials assessing the efficacy of a T. chuii-derived ingredient, characterized by a high superoxide dismutase (SOD) activity (SOD-rich T. chuii), to improve various aspects of cellular health. Collectively, results from in vitro, and more importantly in vivo research, support SOD-rich T. chuii as a potential promoter of cellular health. Principally, the ingredient appears to function as an indirect antioxidant by boosting intracellular antioxidant systems. Moreover, it can positively modulate inflammatory status by up-regulating anti-inflammatory and down-regulating pro-inflammatory cytokines and factors. In addition, SOD-rich T. chuii appears to promote cellular health though protecting from DNA damage, boosting immune function, strengthening cell structure and integrity, and positively modulating cell signaling pathways. There is also some evidence to suggest that SOD-rich T. chuii may improve aspects of mitochondrial function through the up-regulation of genes linked to mitochondrial biogenesis and ATP synthesis. From the trials conducted to date, transcriptional activation of nuclear factor erythroid 2-related factor 2 (NRF2) and sirtuin 1 (SIRT1) appear to be important in mediating the effects of SOD-rich T. chuii on cellular health. These exciting preliminary observations suggest that SOD-rich T. chuii may represent a natural blue food supplement with the potential to enhance various aspects of cellular health.
    Keywords:  SOD; Tetraselmis chuii; anti-inflammatory; antioxidant; cellular health; food supplement
    DOI:  https://doi.org/10.3390/ijms26041693
  34. Int J Biol Macromol. 2025 Feb 21. pii: S0141-8130(25)01883-5. [Epub ahead of print] 141332
    Low molecular weight protein tyrosine phosphatase: A driver of lipid metabolic remodeling in Caenorhabditis elegans.
    Lu An, Bingyu Geng, Lin An, Yue Wang, Zhixia Zhang, Xueqi Fu, Jing Chen, Junfeng Ma.
      As a member of the class II cysteine-based protein tyrosine phosphatases, low molecular weight protein tyrosine phosphatase (LMWPTP) plays a pivotal role in animal physiology, particularly in signaling transduction, but its specific function in lipid metabolism remains poorly understood. Herein, the structure and metabolic functions of LMWPTP were investigated using the Caenorhabditis elegans (C. elegans) as a convenient model. The nematode LMWPTP was found to be highly conserved in sequence, functional domains, and tertiary structure compared to its mammalian homologs. Through RNA interference (RNAi) targeting lmwptp, we observed a modest increase in lipid accumulation in nematodes, evidenced by higher triglyceride levels, enlarged lipid droplets, and an increase in total fatty acid content, despite no changes in body size. Mechanistically, lmwptp RNAi promoted adipogenesis by modulating the insulin-like growth factor 1 signaling pathway, facilitating the nuclear translocation of DAF-16, which in turn upregulated fat-7 expression. Furthermore, increased ROS levels were associated with enhanced lipogenesis. The knockdown of lmwptp also attenuated lipolysis and lipophagy via modulation of the AMPK pathway. Despite these alterations, key physiological functions related to energy metabolism were preserved, and lifespan was extended with delayed aging markers. These findings highlight LMWPTP's significant role in lipid regulation, offering new insights and potential therapeutic targets for human lipid metabolism disorders.
    Keywords:  Autophagy; Caenorhabditis elegans; Insulin/insulin growth factor 1 (IGF-1) signaling pathway; Lipid metabolism; Low molecular weight protein tyrosine phosphatase
    DOI:  https://doi.org/10.1016/j.ijbiomac.2025.141332
  35. Transl Res. 2025 Feb 20. pii: S1931-5244(25)00025-8. [Epub ahead of print]278 36-47
    Effects of senotherapeutics on gut microbiome dysbiosis and intestinal inflammation in Crohn's disease: A pilot study.
    Nannapat Sangfuang, Laura E McCoubrey, Atheer Awad, Massimo Marzorati, Jonas Ghyselinck, Lynn Verstrepen, Julie De Munck, Jelle De Medts, Simon Gaisford, Abdul W Basit.
      Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract, and is usually accompanied by dysbiosis in the gut microbiome, a factor that contributes to disease progression. Excessive production of reactive oxygen species (ROS) because of gut microbiome dysbiosis-one of the hallmark features of IBD-promotes chronic inflammation and facilitates the transformation of normal cells into senescent cells. Cellular senescence is associated with the development of various chronic and age-related diseases. We hypothesise that senolytic agents, specifically dasatinib (D) and quercetin (Q), could have a beneficial effect on both the gut microbiome and intestinal cells in IBD. The modulatory effects of a combination of D + Q was assessed in the M-SHIME model with faecal microbiota sourced from Crohn's disease patients. D + Q significantly modulated butyrate and lactate levels in the samples from specific patients. In addition, metabolomic analysis showed that D + Q positively impacted the abundance of anti-inflammatory bacteria while also significantly reducing the several species of pathogenic bacteria. Findings from a Caco-2 cell/THP1 co-culture model of IBD demonstrated that D + Q exerted strong immunomodulatory effects on the gut epithelium, evidenced by reduced NF-kB activity, and lower levels of the pro-inflammatory markers TNF-α, CXCL-10, and MCP-1. Furthermore, D + Q induced the secretion of anti-inflammatory cytokines, including IL-6 and IL-10. However, it should be noted that D + Q also led to the secretion of the pro-inflammatory cytokines IL-8. These findings suggest that D + Q could offer a novel therapeutic approach for advanced IBD management by modulating both the gut microbiome and inflammatory pathways. The results support the potential repurposing of senotherapeutic agents as a strategy for addressing the chronic inflammation central to IBD pathogenesis.
    Keywords:  Ageing; Gut health; Human gut microbiome, Aged colon; Inflammatory Bowel Disease; Senolytic cocktail; Senotherapeutics; Ulcerative colitis
    DOI:  https://doi.org/10.1016/j.trsl.2025.02.004
  36. Pharmaceuticals (Basel). 2025 Feb 11. pii: 241. [Epub ahead of print]18(2):
    Extraction Optimization and Bioactivity of Polysaccharides from Ganoderma leucocontextum Spores.
    Siying Peng, Yanghui Ou, Yali Zhang, Hongliang Yao, Wen-Hua Chen.
      Background: Oxidative stress is associated with the occurrence and progress of aging. Natural polysaccharides have attracted considerable attention in the field of antioxidants and anti-aging products due to their superior biological activity and low toxicity. Ganoderma leucocontextum is primarily found in the Tibetan plateau region and is classified as a subspecies of Ganoderma. Known as the famous white Ganoderma, it is a precious food and medicine that has potent biological activity, including antitumor, hypoglycemic, and immune regulation. Since available resources are limited, there are few studies on the spore of Ganoderma leucocontextum. Methods: In this work, a polysaccharide (named GLSP) was extracted from the spore of Ganoderma leucocontextum using a fast, simple, efficient, and environmentally friendly extraction process: the three-phase partitioning (TPP) method. Results: The extraction condition was optimized under the Box-Behnken design (BBD): ratio of the solute to the solvent, 1:21.126 (w/v); (NH4)2SO4 concentration, 30% (w/v); ratio of the slurry to tert-butanol, 1:1.945 (v/v); and shaking temperature, 54.136 °C. Furthermore, a polysaccharide termed GLSP-A1 was purified from GLSP by column chromatography. The basic physicochemical properties were analyzed by molecular weight, Fourier transform infrared spectroscopy, monosaccharide composition, and scanning electron microscopy. Conclusions: GLSP-A1 down-regulated the expression of the pro-inflammation cytokines interleukin-6 and interleukin-1β, indicating favorable in vitro anti-inflammatory properties. In vivo, the effect of GLSP-A1 on aging was examined using the Caenorhabditis model. The results showed that GLSP-A1 reduced reactive oxygen species levels and lipofuscin accumulation. In general, these findings improve our understanding of the chemical content and bioactivity of a polysaccharide from Ganoderma leucocontextum spore and highlight the possibility of GLSP-A1 being utilized in dietary supplements for its anti-aging properties.
    Keywords:  Ganoderma leucocontextum spore; anti-aging; anti-inflammation; polysaccharide; three-phase partitioning
    DOI:  https://doi.org/10.3390/ph18020241
  37. Biology (Basel). 2025 Feb 14. pii: 202. [Epub ahead of print]14(2):
    Protective Effects of Centella asiatica Against Senescence and Apoptosis in Epidermal Cells.
    Yu Tan, Ailing Hu, Jingya Lu, Yunhai Lin, Xuejing Li, Takuji Yamaguchi, Masahiro Tabuchi, Zenji Kawakami, Yasushi Ikarashi, Hiroyuki Kobayashi.
      Centella asiatica, a traditional medicinal plant, possesses potent antioxidant activity and may therefore prevent cellular aging and exert antiapoptotic effects. However, these effects remain to be fully elucidated. This study aimed to investigate the protective effects of C. asiatica extract against cellular senescence and apoptosis caused by hydrogen peroxide (H2O2)-induced oxidative stress in human epidermal keratinocytes (HaCaT cells). To evaluate the effects of H2O2 and C. asiatica on HaCaT cells, we measured cell viability as a marker of cell death; reactive oxygen species (ROS), radical scavenging, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities as markers of oxidative stress; senescence-associated β-galactosidase (SA-β-gal) activity as a marker of cellular senescence; and caspase-3/9 activities and apoptotic cells as markers of apoptosis. H2O2 induced cell death (decreased cell viability), oxidative stress (increased ROS activity, decreased radical scavenging, SOD, GPx, and catalase activities), cellular senescence (increased SA-β-gal activity), and apoptosis (increased early/late apoptotic cells and increased caspase-3/9 activities). C. asiatica significantly decreased all markers of H2O2-induced cell death, oxidative stress, cellular senescence, and apoptosis, suggesting its ability to prevent cellular senescence and apoptosis through its antioxidant activity. This mechanism of action may contribute to the prevention and improvement of skin aging.
    Keywords:  Centella asiatica; apoptosis; cellular senescence; keratinocytes; oxidative stress
    DOI:  https://doi.org/10.3390/biology14020202
  38. Pharmaceutics. 2025 Feb 06. pii: 210. [Epub ahead of print]17(2):
    Thymoquinone-Loaded Chitosan Nanoparticles Combat Testicular Aging and Oxidative Stress Through SIRT1/FOXO3a Activation: An In Vivo and In Vitro Study.
    Enas A Kasem, Gehan Hamza, Nagi M El-Shafai, Nora F Ghanem, Shawky Mahmoud, Samy M Sayed, Mohammed Ali Alshehri, Laila A Al-Shuraym, Heba I Ghamry, Magdy E Mahfouz, Mustafa Shukry.
      Background: Aging is a complex biological process characterized by the accumulation of molecular and cellular damage over time, often driven by oxidative stress. This oxidative stress is particularly detrimental to the testes, where it causes degeneration, reduced testosterone levels, and compromised fertility. D-galactose (D-gal) is commonly used to model aging as it induces oxidative stress, mimicking age-related cellular and molecular damage. Testicular aging is of significant concern due to its implications for reproductive health and hormonal balance. This research examines the protection by thymoquinone (TQ) or thymoquinone-loaded chitosan nanoparticles (NCPs) against D-galactose (D-gal)-induced aging in rat testes, focusing on biochemical, histological, and molecular changes. Aging, which is driven largely by oxidative stress, leads to significant testicular degeneration, reducing fertility. D-gal is widely used to model aging due to its ability to induce oxidative stress and mimic age-related damage. TQ, a bioactive ingredient of Nigella sativa, has earned a reputation for its anti-inflammatory, anti-apoptotic, and antioxidant characteristics, but its therapeutic application is limited by its poor bioavailability. Methods: Thymoquinone was loaded into chitosan nanoparticles (NCPs) to enhance its efficacy, and this was hypothesized to improve its stability and bioavailability. Four groups of male Wistar rats participated in the study: one for the control, one for D-gal, one for D-gal + TQ, and the last one for D-gal + NCP. Results: The results exhibited that D-gal substantially increased oxidative injury, reduced testosterone levels, and caused testicular damage. Treatment with TQ and NCPs significantly reduced oxidative stress, improved antioxidant enzyme levels, and restored testosterone levels, with NCPs showing a stronger protective effect than TQ alone. A histological analysis confirmed that NCPs better preserved testicular structure and function. Additionally, the NCP treatment upregulated the expression of key genes of oxidative stress resistance, mitochondrial function, and reproductive health, including SIRT1, FOXO3a, and TERT. Conclusions: The findings suggest that NCPs offer enhanced protection against aging-related testicular damage compared with TQ alone, which is likely due to the improved bioavailability and stability provided by the nanoparticle delivery system. This research emphasizes the potential of NCPs as a more effective therapeutic strategy for mitigating oxidative stress and age-related reproductive dysfunction. Future research should further explore the mechanisms underlying these protective effects.
    Keywords:  D-gal; chitosan nanoparticles; oxidative stress; testicular protection; thymoquinone
    DOI:  https://doi.org/10.3390/pharmaceutics17020210
  39. Front Bioeng Biotechnol. 2025 ;13 1527854
    Advances in regenerative medicine-based approaches for skin regeneration and rejuvenation.
    Nathalia Silva Dutra Alves, Gustavo Roncoli Reigado, Mayara Santos, Izabela Daniel Sardinha Caldeira, Henrique Dos Santos Hernandes, Bruna Leticia Freitas-Marchi, Elina Zhivov, Felipe Santiago Chambergo, Viviane Abreu Nunes.
      Significant progress has been made in regenerative medicine for skin repair and rejuvenation. This review examines core technologies including stem cell therapy, bioengineered skin substitutes, platelet-rich plasma (PRP), exosome-based therapies, and gene editing techniques like CRISPR. These methods hold promise for treating a range of conditions, from chronic wounds and burns to age-related skin changes and genetic disorders. Challenges remain in optimizing these therapies for broader accessibility and ensuring long-term safety and efficacy.
    Keywords:  bioengineered skin substitutes; burns; chronic wounds; regenerative medicine; rejuvenation; skin regeneration; stem cells; wound healing
    DOI:  https://doi.org/10.3389/fbioe.2025.1527854
  40. Geroscience. 2025 Feb 24.
    Awareness, knowledge, and motivations about lifespan, healthspan, and Healthy Longevity Medicine in the general population: the HEalthy LOngevity (HELO) conceptual framework.
    Belinda Wang, Anna Szücs, Elena Sandalova, E J Horberg, Paul A O'Keefe, Louis Island, Hans J Meij, Sonny Rosenthal, Andrea B Maier.
      The global population is ageing and the gap between lifespan (total years lived) and healthspan (years lived free of diseases) is increasing. Healthy Longevity Medicine (HLM) is an approach to optimise health and healthspan, and it has substantial public health implications. Despite those implications, the understanding of public perspectives on this field is lacking. The HEalthy LOngevity (HELO) framework was developed through a literature review guided by expert discussions across disciplines to include evidence-based concepts of health-related decision-making, ageing, and HLM. The framework organises concepts into three components. The first two components, awareness and knowledge, explore public perception and understanding of the healthy longevity field, respectively. The third component, motivations, reflects factors underlying motivations towards healthy longevity. These include personality, current behaviours, personal values and beliefs, and health-related perceptions. The framework outlines the theoretical foundation to explore public knowledge and interest in healthy longevity. The framework will be refined based on findings from qualitative focus groups in Singapore and then applied to quantitative population surveys globally. These HELO initiatives aim to inform strategies for integrating HLM into public healthcare, promoting health and healthspan.
    Keywords:  Aging; Awareness; Healthspan; Lifespan; Longevity; Motivation
    DOI:  https://doi.org/10.1007/s11357-025-01562-4
  41. Biogerontology. 2025 Feb 26. 26(2): 65
    Harnessing the FOXO-SIRT1 axis: insights into cellular stress, metabolism, and aging.
    Saurabh Gupta, Muhammad Afzal, Neetu Agrawal, Waleed Hassan Almalki, Mohit Rana, Saurabh Gangola, Suresh V Chinni, Benod Kumar K, Haider Ali, Sachin Kumar Singh, Saurabh Kumar Jha, Gaurav Gupta.
      Aging and metabolic disorders share intricate molecular pathways, with the Forkhead box O (FOXO)- Sirtuin 1 (SIRT1) axis emerging as a pivotal regulator of cellular stress adaptation, metabolic homeostasis, and longevity. This axis integrates nutrient signaling with oxidative stress defence, modulating glucose and lipid metabolism, mitochondrial function, and autophagy to maintain cellular stability. FOXO transcription factors, regulated by SIRT1 deacetylation, enhance antioxidant defence mechanisms, activating genes such as superoxide dismutase (SOD) and catalase, thereby counteracting oxidative stress and metabolic dysregulation. Recent evidence highlights the dynamic role of reactive oxygen species (ROS) as secondary messengers in redox signaling, influencing FOXO-SIRT1 activity in metabolic adaptation. Additionally, key redox-sensitive regulators such as nuclear factor erythroid 2-related factor 2 (Nrf2) and Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) interact with this pathway, orchestrating mitochondrial biogenesis and adaptive stress responses. Pharmacological interventions, including alpha-lipoic acid (ALA), resveratrol, curcumin and NAD+ precursors, exhibit therapeutic potential by enhancing insulin sensitivity, reducing oxidative burden, and restoring metabolic balance. This review synthesizes current advancements in FOXO-SIRT1 regulation, its emerging role in redox homeostasis, and its therapeutic relevance, offering insights into future strategies for combating metabolic dysfunction and aging-related diseases.
    Keywords:  Aging; Autophagy; Cellular stress; DNA damage; FOXO; Metabolism; SIRT1
    DOI:  https://doi.org/10.1007/s10522-025-10207-0
  42. Sci Rep. 2025 Feb 25. 15(1): 6780
    Efficacy of Naringenin against aging and degeneration of nucleus pulposus cells through IGFBP3 inhibition.
    Xiaokai Tang, Junlong Zhong, Hao Luo, Faxin Zhou, Lixia Wang, Sijian Lin, Jiachao Xiong, Hao Lv, Zhenhai Zhou, Honggui Yu, Kai Cao.
      Naringenin (NAR), a natural flavonoid, exerts anti-inflammatory and antioxidant pharmacology. However, the pharmacological mechanisms through which NAR prevents and treats intervertebral disc degeneration (IDD) remain unclear. We utilized bioinformatics, machine learning, and network pharmacology to identify shared targets among NAR, senescence, and IDD. Subsequently, molecular docking was conducted to evaluate NAR's binding affinity to common target. Additionally, we used IL-1β to induce senescence and degeneration in nucleus pulposus cells (NPCs) and conducted a series of cellular assays, including immunoblotting, immunofluorescence, β-galactosidase staining, cell proliferation, cell cycle analysis, and measurement of reactive oxygen species levels, to investigate NAR's impact on IL-1β-induced senescence and degeneration of NPCs. Our study revealed that Insulin-like growth factor binding protein 3 (IGFBP3) was the only common target. IGFBP3 exhibited significant differences between the IDD and healthy groups and proved to be an effective diagnostic marker for IDD. Molecular docking confirmed the binding between NAR and IGFBP3. In vitro experiments, we observed that Igfbp3 expression increased in the senescence and degeneration groups. Igfbp3 knockdown and NAR attenuated IL-1β-induced senescence and degenerative phenotypes in NPCs. In contrast, the effect of NAR was attenuated by recombinant IGFBP3 protein. In conclusion, our findings suggest that NAR plays a preventive and therapeutic role in IDD, likely achieved through the inhibition of Igfbp3 expression.
    Keywords:  Aging and degeneration; Intervertebral disc degeneration; Machine learning; Naringenin; Network pharmacology
    DOI:  https://doi.org/10.1038/s41598-025-90909-0
  43. J Physiol. 2025 Feb 26.
    Dietary nitrate supplementation mitigates age-related changes at the neuromuscular junction in mice.
    Maira Rossi, Lucrezia Zuccarelli, Lorenza Brocca, Cristiana Sazzi, Clarissa Gissi, Paola Rossi, Bruno Grassi, Simone Porcelli, Roberto Bottinelli, Maria Antonietta Pellegrino.
      In ageing, denervation and neuromuscular junction (NMJ) instability occur alongside mitochondrial alterations and redox unbalance, potentially playing a significant role in the process. Moreover, the synthetic pathway was shown to be critical for proper innervation and NMJ stability. Nitric oxide (NO) modulates redox status, mitochondrial function and the synthetic pathway. Its bioavailability declines with age. We hypothesize that nitrate supplementation could counteract age-related neuromuscular alterations. We compared young (Y) (7 months old), old (O) (24 months old) and old mice supplemented daily with 1.5 mm inorganic NaNO3 dissolved in drinking water for 8 weeks (ON) (24 months old). Compared to Y, O mice displayed impaired NO signalling and transport (lower phosphorylated-neuronal NO synthase and sialin content); greater nitrosative and oxidative stress (higher 3-nitrotyrosine levels and protein carbonylation); lower glutathione peroxidase (GPX antioxidant enzyme); smaller muscle fibres; and larger muscle fibrosis. NMJ integrity was impaired, exhibiting age-related alterations such as larger fragmentation, lower overlap, larger endplate areas and lower compactness. Consistently, greater expression of denervation-associated markers (Gadd45α, MyoG, RUNX1, AChRγ and NCAM1) and higher NCAM1+ fibres percentage suggested denervation. Importantly, mitochondrial content, dynamics and function were unchanged. Compared to O, ON mice showed improved NO bioavailability in muscle (higher nitrate-nitrite concentration); lower fibrosis and improved muscle fibre size; higher phosphorylation of P70S6K and S6, downstream factors of Akt/mammalian target of rapamycin synthetic pathway; lower oxidative stress (lower carbonylated proteins and mitochondrial hydrogen peroxide production, higher GPX protein levels); reverted age-related alterations of NMJ morphology; and lower percentage of NCAM1+ fibres. Nitrate supplementation could be a therapeutic strategy to counteract muscle decline with ageing. KEY POINTS: Ageing leads to instability at the neuromuscular junction (NMJ), which is crucial for muscle size and function, ultimately giving rise to denervation and muscle fibres loss. Mitochondrial function, redox status and activation of synthetic pathway are critical processes for proper muscle innervation and stability of the NMJ. Nitric oxide was shown to modulate intracellular processes involved in NMJ stability such as balance of reactive oxygen species, mitochondrial function and protein synthesis. Its bioavailability decreases with ageing. Our study shows that nitrate supplementation in old mice improved redox balance, enhanced the anabolic pathway and stabilized nerve-muscle interactions, suggesting a potential strategy to mitigate the neuromuscular decline associated with ageing.
    Keywords:  ageing; extensor digitorum longus; gastrocnemius; mitochondria; neuromuscular junction; nitrate supplementation; oxidative stress; tibialis anterior
    DOI:  https://doi.org/10.1113/JP287592
  44. Geroscience. 2025 Feb 27.
    Restoring neuropetide Y levels in the hypothalamus ameliorates premature aging phenotype in mice.
    Marisa Ferreira-Marques, Sara Carmo-Silva, Joana Pereira, Mariana Botelho, Clévio Nóbrega, Carlos López-Otín, Luís Pereira de Almeida, Célia A Aveleira, Cláudia Cavadas.
      The hypothalamus has been recognized as a regulator of whole-body aging. Neuropeptide Y (NPY), highly abundant in the central nervous system and produced by the hypothalamus, enhances autophagy in this brain region and mediates autophagy triggered by caloric restriction, suggesting a potential role as a caloric restriction mimetic and an aging regulator. Considering that hypothalamic NPY levels decline during aging, we investigated if reestablishment of NPY levels mitigate aging phenotype, using a mouse model of premature aging - Zmpste24-/- mouse. The results show that reestablishing hypothalamic NPY levels delayed aging-associated features, including lipodystrophy, alopecia, and memory. Moreover, these results suggest that strategies that promote maintenance of hypothalamic NPY levels might be relevant to counteract aging progression and age-related deteriorations.
    Keywords:  Biology of aging; Brain aging; Hypothalamus; Neuropeptide Y
    DOI:  https://doi.org/10.1007/s11357-025-01574-0
  45. Biomater Sci. 2025 Feb 27.
    Lactobacillus-derived artificial extracellular vesicles for skin rejuvenation and prevention of photo-aging.
    Seongsu Kang, Saetbyeol Jeon, Hwira Baek, Sunghwan Hwang, Seulgi Kim, Sung Hun Youn, Jin Woong Kim, Seung-Hyun Jun, Nae-Gyu Kang.
      Extracellular vesicles (EVs) are small membrane-bound sacs released by cells that play crucial roles in intercellular communication. They transport biomolecules between cells and have both diagnostic and therapeutic potential. Artificial EVs, designed to mimic natural EVs, have been developed using various methods. In this study, Lactobacillus plantarum was used to create Lactobacillus-derived artificial EVs (LAEs) for skin rejuvenation and anti-aging. LAEs demonstrated monodispersity and effectively improved adverse gene expression and wound healing in fibroblasts. They also modulated aging-related genes and improved skin conditions in humans. Their simplicity, promptness, and lack of animal-derived sources make LAEs a promising alternative to natural EVs. LAEs have the potential to overcome the technical limitations of artificial EVs and advance EVs or exosome-based technologies for comprehensive skin rejuvenation.
    DOI:  https://doi.org/10.1039/d4bm01644k
  46. Hum Cell. 2025 Feb 25. 38(2): 61
    Fetal adnexa-derived allogeneic mesenchymal stem cells for cardiac regeneration: the future trend of cell-based therapy for age-related adverse conditions.
    Fazel Gorjipour, Sepideh Bohloolighashghaei, Mohammadjavad Sotoudeheian, Hamidreza Pazoki Toroudi.
      Heart failure is known as the leading cause of mortality and morbidity in adults, not only in USA but worldwide. Since the world's population is aging, the burden of cardiovascular disorders is increasing. Mesenchymal stem/stromal cells (MSCs) from a patient's bone marrow or other tissues have been widely used as the primary source of stem cells for cellular cardiomyoplasty. The incongruencies that exist between various cell-therapy approaches for cardiac diseases could be attributed to variations in cell processing methods, quality of the process, and cell donors. Off-the-shelf preparations of MSCs, enabled by batch processing of the cells and controlled cell processing factories in regulated facilities, may offer opportunities to overcome these problems. In this study, for the first time, we focused on the fetal membranes and childbirth byproducts as a promising source of cells for regenerative medicine. While many studies have described the advantages of cells derived from these organs, their advantage as a source of younger cells has not been sufficiently covered by the literature. Thus, herein, we highlight challenges that may arise from the impairment of the regenerative capacity of MSCs due to donor age and how allograft cells from fetal adnexa can be a promising substitute for the aged patients' stem cells for myocardial regeneration. Moreover, obstacles to the use of off-the-shelf cell-therapy preparations in regenerative medicine are briefly summarized here.
    Keywords:  Aging; Cardiovascular disease; Cell- and tissue-based therapy; Extra-embryonic membranes; Heart failure; Mesenchymal stem cells
    DOI:  https://doi.org/10.1007/s13577-025-01190-2
  47. Pharmacol Res. 2025 Feb 25. pii: S1043-6618(25)00100-8. [Epub ahead of print] 107675
    Plant-Derived Nanovesicles as Novel Nanotherapeutics for Alleviating Endothelial Cell Senescence-Associated Vascular Remodeling Induced by Hypertension.
    Fengxia Lin, Luhua Xu, Qiuting He, Zetao Chen, Weiwei Zhang, Jin Tu, Yinzhi Song, Fanjia Zhong, Sheng Lin, Rongfeng Yang, Zhicong Zeng.
      Endothelial cell senescence contributes to vascular remodeling in hypertension, a condition that lacks specific clinical treatments. While plant-derived nanovesicles have shown anti-inflammatory properties that reduce endothelial inflammation, their role in endothelial cell senescence is less understood. Here, we isolated and purified nanovesicles from Semen Sinapis Albae (SDNVs), a traditional Chinese medicine with antihypertensive properties, and evaluated their therapeutic effects on vascular remodeling in spontaneously hypertensive rats (SHRs) compared to nifedipine, a standard antihypertensive drug. SDNVs were as effective as nifedipine in reducing blood pressure and exceeded nifedipine in mitigating vascular wall thickening, collagen fiber disarray, and in decreasing senescence markers in aortic tissues. In vitro, SDNVs inhibited angiotensin II-induced senescence in human umbilical vein endothelial cells (HUVECs). miRNA and mRNA sequencing revealed that SDNVs downregulate CD38 expression through miR393a delivery, mediating their anti-senescence effects. Our results suggest that SDNVs significantly alleviate hypertension-associated vascular remodeling by targeting CD38 via miR393a, thus reducing endothelial cell senescence. Compared to conventional drugs like nifedipine, SDNVs offer a potentially more effective approach to vascular remodeling. These insights may guide the development of novel therapeutics for hypertension-induced vascular remodeling.
    Keywords:  CD38; Hypertension; MicroRNAs; Plant-Derived Nanovesicles; Senescence
    DOI:  https://doi.org/10.1016/j.phrs.2025.107675
  48. Bone Joint Res. 2025 Feb 25. 14(2): 143-154
    Occurrence of cellular senescence in chronic human shoulder tendinopathies and its attenuation ex vivo by inhibition of Enhancer of Zeste 2.
    Dominik Bühler, Morgane Hilpert, Andrea Barbero, Andreas M Müller, Sebastian A Müller, Ivan Martin, Karoliina Pelttari.
       Aims: Our aim was to investigate occurrence of senescent cells directly in tendon tissue biopsies from patients with chronic shoulder tendinopathies, and to correlate senescence with Enhancer of zeste 2 (EZH2) expression, the functional subunit of the epigenetic master regulator polycomb repressive complex.
    Methods: Human proximal long head of biceps tendons from patients with different chronic shoulder pathologies (n = 22), and controls from patients with humerus fracture (n = 6) and pathology (n = 4), were histologically scored for degeneration and analyzed for gene and protein expression of tendon specific factors, senescence markers, and EZH2. Tissues were further exposed to senotherapeutic compounds and the USA Food and Drugs Administration-approved selective EZH2 inhibitor EPZ-6438 and their senescence-associated secretory phenotype (SASP) assessed.
    Results: Expression of senescence markers (CDKN2A/p16, CDKN2D/p19) and EZH2 was significantly higher in tendinopathies compared to fracture or healthy tissue controls and positively correlated with the degree of tissue degeneration. Immunofluorescent stainings demonstrated colocalization of p16 and p19 with EZH2 in tenocytes. Treatment of tendon biopsies with EPZ-6438 reduced secretion of a panel of SASP factors, including interleukin-6 (IL6), IL8, matrix metalloproteinase-3 (MMP3) or GRO1, similarly to the senotherapeutic compound AG490.
    Conclusion: We demonstrate that senescence traits accumulate in pathological tendon tissues and positively correlate with tissue degeneration. Increased expression of CDKN2A/p16 and CDKN2D/p19 coincides with EZH2 expression, while its inhibition decreased the secretion of SASP factors, indicating a possible regulatory role of EZH2 in tenocyte senescence in tendinopathies. Reduction of cellular senescence, e.g. with EPZ-6438, opens ways to new potential therapeutic approaches for enhancing regeneration in chronic tendinopathies.
    DOI:  https://doi.org/10.1302/2046-3758.142.BJR-2023-0378.R2
  49. Sci Rep. 2025 Feb 26. 15(1): 6979
    N-benzyl-N-methyldecane-1-amine derived from garlic ameliorates UVB-induced photoaging in HaCaT cells and SKH-1 hairless mice.
    Phatcharaporn Budluang, Ji Eun Kim, Eun Seo Park, Ayun Seol, Hee Jeong Jang, Moon Sung Kang, Yeon Ha Kim, Jongdoo Choi, Seonghye Kim, Suhkmann Kim, Minseob Koh, Ho Young Kang, Bae-Hwan Kim, Dong-Wook Han, Dae Youn Hwang, Young-Hwa Chung.
      Skin tissue is susceptible to oxidative stress-induced senescence provoked by ultraviolet (UV) exposure in our daily lives, resulting in photoaging. Herein, we explore whether N-benzyl-N-methyldecan-1-amine (BMDA) derived from garlic ameliorates UVB-induced photoaging. To address this issue, HaCaT keratinocytes were exposed to UVB irradiation under BMDA treatment. The presence of BMDA substantially reduced UVB-induced ROS levels in a dose-dependent manner. BMDA administration counteracted UVB-induced senescence in the β-galactosidase assay. Treatment with BMDA also rescued UVB-exposed cells (S phase; from 18.3 to 25.8%) from cell cycle arrest, similar to the level observed in untreated normal cells. These findings might support our observation that elevated levels of γ-H2AX, a DNA damage marker, under UVB exposure were reduced following BMDA administration. Additionally, BMDA treatment indirectly reduced UVB-induced melanin synthesis in melanocytes since BMDA failed to inhibit tyrosinase activity, a crucial enzyme in melanin synthesis. The topical application of BMDA on the skin of SKH-1 hairless mice also diminished wrinkle formation, supported by recovered collagen levels and the thickness of the epidermis and dermis, compared to those of UVB-control mice. Finally, the BMDA treatment diminished the expression of inflammatory cytokine transcripts such as TNF-α, IL-1β, IL-4, and IL-6 in the UVB-exposed skin tissues. This finding is further supported by Immunofluorescence microscopy, which showed a decrease in the expression of TNF-α, and IL-1β during BMDA treatment. Altogether, as BMDA mitigates UVB-induced photoaging by reducing ROS production, protecting against DNA damage, and suppressing inflammatory cytokine production, it has been proposed as an effective anti-photoaging molecule.
    Keywords:  Anti-oxidation; N-benzyl-N-methyldecan-1-amine; Photoaging; Skin; UVB
    DOI:  https://doi.org/10.1038/s41598-025-88634-9
  50. Pharmaceuticals (Basel). 2025 Feb 02. pii: 202. [Epub ahead of print]18(2):
    Discovering the Potential of Cannabidiol for Cosmeceutical Development at the Cellular Level.
    Natjira Tassaneesuwan, Mattaka Khongkow, Siriyakorn Jansrinual, Pasarat Khongkow.
      Backgrounds: Cannabidiol (CBD) has been used for the development of extensive cosmeceutical commercial products. However, the safety and unclear bioactivity of CBD are still concerns and need to be examined to assess the impact of CBD on skin cells through cosmeceutical applications, particularly its impact on anti-aging and wound healing activities. Methods: In our study, the cytotoxicity of CBD was investigated on keratinocytes and fibroblasts in short-term and long-term treatments using a sulforhodamine B (SRB) assay and a clonogenic assay, respectively. Next, the antioxidant, anti-aging, and wound healing bioactivities of CBD were assessed. Then, we investigated the expression of the related genes. Results: Our results show that CBD at low concentrations (0.625-2.5 µg/mL) was not toxic to cells in the short-term treatment and significantly enhanced the growth of keratinocytes and fibroblasts under long-term exposure. Furthermore, CBD exhibited promising cellular bioactivities, including antioxidant and anti-aging activities in keratinocytes and fibroblasts, and it enhanced wound healing in skin cells. Moreover, CBD has affected the expression of skin regenerative genes in fibroblasts via TGF-β, VEGF, and NF-κB expression. In addition, CBD promoted CO1A2 expression, which is related to collagen production. Conclusions: Altogether, our findings confirm the promising potential of CBD, showing that it can be applied in various topical cosmeceutical products. However, further studies, including in vivo studies and clinical trials, should be conducted to confirm the safety and long-term effectiveness of CBD on the skin.
    Keywords:  CBD; anti-aging; bioactivity; cannabidiol; cosmetics; cytotoxicity; skin cells
    DOI:  https://doi.org/10.3390/ph18020202
  51. Autophagy. 2025 Feb 23.
    Autophagy regulates cellular senescence by mediating the degradation of CDKN1A/p21 and CDKN2A/p16 through SQSTM1/p62-mediated selective autophagy in myxomatous mitral valve degeneration.
    Qiyu Tang, Keyi Tang, Greg R Markby, Maciej Parys, Kanchan Phadwal, Vicky E MacRae, Brendan M Corcoran.
      Myxomatous mitral valve degeneration (MMVD) is one of the most important age-dependent degenerative heart valve disorders in both humans and dogs. It is characterized by the aberrant remodeling of extracellular matrix (ECM), regulated by senescent myofibroblasts (aVICs) transitioning from quiescent valve interstitial cells (qVICs), primarily under TGFB1/TGF-β1 control. In the present study, we found senescent aVICs exhibited impaired macroautophagy/autophagy as evidenced by compromised autophagy flux and immature autophagosomes. MTOR-dependent autophagy induced by rapamycin and torin-1 attenuated cell senescence and decreased the expression of cyclin-dependent kinase inhibitors (CDKIs) CDKN2A/p16INK4A and CDKN1A/p21CIP1. Furthermore, induction of autophagy in aVICs by ATG (autophagy related) gene overexpression restored autophagy flux, with a concomitant reduction in CDKN1A and CDKN2A expression and senescence-associated secretory phenotype (SASP). Conversely, autophagy deficiency induced CDKN1A and CDKN2A accumulation and SASP, whereas ATG re-expression alleviated senescent phenotypic transformation. Notably, CDKN1A and CDKN2A localized to autophagosomes and lysosomes following MTOR antagonism or MG132 treatment. SQSTM1/p62 was identified as the autophagy receptor to selectively sequester CDKN1A and CDKN2A cargoes for autophagic degradation. Our findings are the first demonstration that CDKN1A and CDKN2A are degraded through SQSTM1-mediated selective autophagy, independent of the ubiquitin-proteasome pathway. These data will inform development of therapeutic strategies for the treatment of canine and human MMVD, and for the treatment of Alzheimer disease, Parkinson disease and other age-related degenerative disorders.
    Keywords:  Autophagic degradation; CDKI; MMVD; SASP; TGFB; ubiquitin-proteasome pathway
    DOI:  https://doi.org/10.1080/15548627.2025.2469315
  52. Biology (Basel). 2025 Feb 01. pii: 149. [Epub ahead of print]14(2):
    Selectively Blocking Small Conductance Ca2+-Activated K+ Channels Improves Cognition in Aged Mice.
    Jessie Ong, H Craig Heller, Elsa Pittaras.
      Aging is associated with decreased neuronal sensitivity and activity that creates deficits in cognitive processes, including learning, memory, motivation, general activity, and other behaviors. These effects are due in part to decreased intracellular Ca2+ homeostasis, increasing hyperpolarization of the resting potential in aged neurons and therefore decreasing their excitability. To reduce hyperpolarization in aged mice, we used apamin, a selective small conductance Ca2+-activated K+ (sKCa) channel blocker. By blocking the sKCa channels, apamin decreases the egress of the K+ out of the cell, reducing its hyperpolarization and causing it to be closer to threshold potential. As a result, neurons should be more sensitive to excitatory stimuli and more active. We evaluated the performance of aged mice in a selection of cognitive and behavioral tests prior to and after systemic applications of apamin or the vehicle saline. Apamin improved performance in short-term memory, increased attention to tasks, and decreased anhedonia. Apamin had no significant effect on long-term spatial and recognition memory, risk-taking behavior, sociability, and anxiety. Our results are compatible with the known effects of sKCa channel blockade on neuronal sensitivity and activity; however, these short-term effects were not reflected in longer-term alterations of neural plasticity responsible for long-term spatial and recognition memory or other more complex cognitive processes we evaluated.
    Keywords:  K+ channel; anxiety; apamin; memory; motivation; motor skills; risk taking
    DOI:  https://doi.org/10.3390/biology14020149
  53. Geriatrics (Basel). 2025 Feb 18. pii: 31. [Epub ahead of print]10(1):
    Preventive Pathways for Healthy Ageing: A Systematic Literature Review.
    Alice Masini, Niccolò Cherasco, Andrea Conti, Irlanda Pighini, Francesco Barone-Adesi, Massimiliano Panella.
      Background: The world's population is not only growing but also ageing, and healthcare systems should adapt to the needs of an ageing population. Until now, there has been no clear definition of a preventive pathway with the aim of improving lifestyles and promoting healthy and active ageing. The present systematic review aims to provide evidence to support the development of effective ways of delivering preventive pathways for healthy ageing. Methods: Several databases were searched, i.e., MEDLINE, COCHRANE, CINAHL, and PsycINFO, by using specific inclusion criteria, such as elderly population (i.e., subjects aged 65 years and older), preventive interventions for healthy ageing, studies with or without control groups, and effectiveness and methodological structure of the prevention pathway. The risk of bias was assessed by using the Joanna Briggs Institute and mixed methods appraisal tools. Results: A total of 9998 studies were identified after the removal of duplicates, and after screening title, abstracts, and full text, 14 studies were finally included. All the prevention pathways described are based on physical activity (PA) programmes, dietary interventions, and cognitive and mental health. The professional figures involved in the pathways were experts in prevention and health promotion, like family and community nurses, kinesiologists, and experts in stress management. The majority of the preventive pathways were implemented in primary care and community settings. Conclusions: Our systematic review provides evidence for developing an effective preventive healthy ageing pathway through tailored PA, diet, and cognitive health interventions. This co-designed approach should involve a multidisciplinary expert team and be implemented in primary care and community settings to improve psycho-physical health and longevity.
    Keywords:  active ageing; elderly; health promotion; healthy ageing; lifestyle interventions; preventive pathways; systematic literature review
    DOI:  https://doi.org/10.3390/geriatrics10010031
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