bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2024–12–01
23 papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño
  1. Serine metabolism in aging and age-related diseases.
  2. Old Cells Need New Rules: New Guidelines for Senescent Cell Experimentation In Vivo.
  3. Impacts of Senolytic Phytochemicals on Gut Microbiota: A Comprehensive Review.
  4. Exploring mechanisms of skin aging: insights for clinical treatment.
  5. Asparagine prevents intestinal stem cell aging via the autophagy-lysosomal pathway.
  6. Endogenous chondroitin extends lifespan by inhibiting VHA-7-mediated tubular lysosome formation.
  7. Influences on Skin and Intrinsic Aging: Biological, Environmental, and Therapeutic Insights.
  8. Organoids as Tools for Investigating Skin Aging: Mechanisms, Applications, and Insights.
  9. Senataxin Attenuates DNA Damage Response Activation and Suppresses Senescence.
  10. Fecal Microbiota Transplantation, a tool to transfer healthy longevity.
  11. Ca2+/calmodulin signaling in organismal aging and cellular senescence: Impact on human diseases.
  12. Marine-Derived Bioactive Ingredients in Functional Foods for Aging: Nutritional and Therapeutic Perspectives.
  13. The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies.
  14. Inhibition of the E3 ligase UBR5 stabilizes TERT and protects vascular organoids from oxidative stress.
  15. Anti-Inflammatory and Autophagy Activation Effects of 7-Methylsulfonylheptyl Isothiocyanate Could Suppress Skin Aging: In Vitro Evidence.
  16. Telomere function and regulation from mouse models to human ageing and disease.
  17. Optimization and Implication of Adipose-Derived Stem Cells in Craniofacial Bone Regeneration and Repair.
  18. DNA sequence and lesion-dependent mitochondrial transcription factor A (TFAM)-DNA-binding modulates DNA repair activities and products.
  19. Action-At-A-Distance in DNA Mismatch Repair: Mechanistic Insights and Models for How DNA and Repair Proteins Facilitate Long-Range Communication.
  20. Immune Alterations with Aging: Mechanisms and Intervention Strategies.
  21. High exposure to carrageenan in young mice may impair behavior, immunity, redox and inflammatory states throughout the aging process.
  22. Age-Related ECM Stiffness Mediates TRAIL Activation in Muscle Stem Cell Differentiation.
  23. Ginseng and ginseng byproducts for skincare and skin health.
  1. Geroscience. 2024 Nov 25.
    Serine metabolism in aging and age-related diseases.
    Shengshuai Shan, Jessica M Hoffman.
      Non-essential amino acids are often overlooked in biomedical research; however, they are crucial components of organismal metabolism. One such metabolite that is integral to physiological function is serine. Serine acts as a pivotal link connecting glycolysis with one-carbon and lipid metabolism, as well as with pyruvate and glutathione syntheses. Interestingly, increasing evidence suggests that serine metabolism may impact the aging process, and supplementation with serine may confer benefits in safeguarding against aging and age-related disorders. This review synthesizes recent insights into the regulation of serine metabolism during aging and its potential to promote healthy lifespan and mitigate a spectrum of age-related diseases.
    Keywords:  Age-related diseases; Aging; Longevity; Metabolism; Oxidative stress; Serine
    DOI:  https://doi.org/10.1007/s11357-024-01444-1
  2. J Invest Dermatol. 2024 Nov 27. pii: S0022-202X(24)02814-8. [Epub ahead of print]
    Old Cells Need New Rules: New Guidelines for Senescent Cell Experimentation In Vivo.
    Florian Gruber, Christopher Kremslehner.
      
    Keywords:  Aging; Cellular senescence; SASP; Senescence; Skin aging
    DOI:  https://doi.org/10.1016/j.jid.2024.10.590
  3. J Microbiol Biotechnol. 2024 Nov 28. 34(11): 2166-2172
    Impacts of Senolytic Phytochemicals on Gut Microbiota: A Comprehensive Review.
    Hee Soo Kim, Chang Hwa Jung.
      There is increasing interest in utilizing senolytics to selectively remove senescent cells from intestinal tissues, with the aim of maintaining a healthy gut environment during aging. This strategy underscores the potential of senolytics to enhance gut health by delaying intestinal aging and positively modulating gut microbiota. Certain plant-based phytochemicals have demonstrated promising senolytic effects. Beyond their ability to eliminate senescent cells, these compounds also exhibit antioxidant and anti-inflammatory properties, reducing oxidative stress and inflammation-key drivers of age-related diseases. By selectively removing senescent cells from the intestine, senolytic phytochemicals contribute to an improved intestinal inflammatory environment and promote the growth of a diverse microbial community. Ultimately, the dietary intake of these senolytic phytochemicals aids in maintaining a healthier intestinal microenvironment by targeting and clearing aged enterocytes.
    Keywords:  Senolytic; aging; gut; phytochemical; senescence
    DOI:  https://doi.org/10.4014/jmb.2408.08032
  4. Front Immunol. 2024 ;15 1421858
    Exploring mechanisms of skin aging: insights for clinical treatment.
    Meiqi Zhang, Yumeng Lin, Zhongyu Han, Xuewen Huang, Shuwei Zhou, Siyu Wang, Yan Zhou, Xuan Han, Haoran Chen.
      The skin is the largest organ in the human body and is made up of various cells and structures. Over time, the skin will age, which is not only influenced by internal factors, but also by external environmental factors, especially ultraviolet radiation. Aging causes immune system weakening in the elderly, which makes them more susceptible to dermatosis, such as type 2 inflammatory mediated pruritus. The immune response in this condition is marked by senescent cells consistently releasing low amounts of pro-inflammatory cytokines through a senescence-associated secretory phenotype (SASP). This continuous inflammation may accelerate immune system aging and establish a connection between immune aging and type 2 inflammatory skin diseases. In addition, two chronic pigmentation disorders, vitiligo and chloasma, are also associated with skin aging. Aged cells escape the immune system and accumulate in tissues, forming a microenvironment that promotes cancer. At the same time, "photoaging" caused by excessive exposure to ultraviolet radiation is also an important cause of skin cancer. This manuscript describes the possible links between skin aging and type 2 inflammation, chronic pigmentation disorders, and skin cancer and suggests some treatment options.
    Keywords:  aging; chronic pigmentary disorders; skin; skin cancer; type 2 inflammatory
    DOI:  https://doi.org/10.3389/fimmu.2024.1421858
  5. Aging Cell. 2024 Nov 25. e14423
    Asparagine prevents intestinal stem cell aging via the autophagy-lysosomal pathway.
    Ting Luo, Liusha Zhao, Chenxi Feng, Jinhua Yan, Yu Yuan, Haiyang Chen.
      The age-associated decline in intestinal stem cell (ISC) function is a key factor in intestinal aging in organisms, resulting in impaired intestinal function and increased susceptibility to age-related diseases. Consequently, it is imperative to develop effective therapeutic strategies to prevent ISC aging and functional decline. In this study, we utilized an aging Drosophila model screening of amino acids and found that asparagine (Asn), a nonessential amino acid in vivo, exhibits its profound anti-aging properties on ISCs. Asn inhibits the hyperproliferation of aging ISCs in Drosophila, maintains intestinal homeostasis, and extends the lifespan of aging flies. Complementarily, Asn promotes the growth and branching of elderly murine intestinal organoids, indicating its anti-aging capacity to enhance ISC function. Mechanistic analyses have revealed that Asn exerts its effects via the activation of the autophagic signaling pathway. In summary, this study has preliminarily explored the potential supportive role of Asn in ameliorating intestinal aging, providing a foundation for further research into therapeutic interventions targeting age-related intestinal dysfunction.
    Keywords:   Drosophila ; aging; asparagine; autophagy; gut; intestinal stem cell
    DOI:  https://doi.org/10.1111/acel.14423
  6. Sci Rep. 2024 Nov 29. 14(1): 29651
    Endogenous chondroitin extends lifespan by inhibiting VHA-7-mediated tubular lysosome formation.
    Yukimasa Shibata, Yuri Tanaka, Shunsuke Mori, Kaito Mitsuzumi, Shion Fujii, Hiroyuki Sasakura, Yuki Morioka, Kenji Sugioka, Kosei Takeuchi, Kiyoji Nishiwaki.
      Chondroitin extends lifespan and healthspan in C. elegans, but the relationship between extracellular chondroitin and intracellular anti-aging mechanisms is unknown. The basement membrane (BM) that contains chondroitin proteoglycans is anchored to cells via hemidesmosomes (HDs), and it accumulates damage with aging. In this study, we found that chondroitin regulates aging through the formation of HDs and inhibition of tubular lysosomes (TLs). Reduction of chondroitin due to a mutation in sqv-5/Chondroitin synthase (ChSy) causes the earlier and excessive formation of TLs and leakage of the lysosomal nuclease in a manner dependent on VHA-7, the a-subunit of V-type ATPase. VHA-7, whose mutation suppresses the short lifespan of the sqv-5 mutant, is initially localized to the basal side of the hypodermal cells and transported to lysosomes with aging. These results demonstrate that endogenous chondroitin suppresses aging by inhibiting the earlier excessive formation of TLs. This is a novel anti-aging mechanism that is controlled by the BM.
    Keywords:  Aging; Basement membrane; Chondroitin; Hemidesmosomes; Tubular lysosomes
    DOI:  https://doi.org/10.1038/s41598-024-80242-3
  7. J Cosmet Dermatol. 2024 Nov 27. e16688
    Influences on Skin and Intrinsic Aging: Biological, Environmental, and Therapeutic Insights.
    Ramadan S Hussein, Salman Bin Dayel, Othman Abahussein, Abeer Ali El-Sherbiny.
       BACKGROUND/AIM: Aging involves a progressive deterioration in physiological functions and increased disease susceptibility, impacting all organs and tissues, especially the skin. Skin aging is driven by intrinsic factors (genetics, cellular metabolism) and extrinsic factors (environment, lifestyle). Understanding these mechanisms is vital for promoting healthy aging and mitigating skin aging effects. This review aims to summarize the key factors influencing skin and intrinsic aging, providing a comprehensive understanding of the underlying mechanisms and contributing elements.
    METHODS: A comprehensive literature review was conducted, focusing on peer-reviewed journals, clinical studies, and scientific reviews published within the last two decades. The inclusion criteria prioritized studies that addressed intrinsic and extrinsic mechanisms of skin aging. To ensure the relevance and quality of the selected sources, a systematic approach was used to assess study design, sample size, methodology, and the significance of the findings in the context of skin aging.
    FINDINGS: The review identifies major internal factors, such as cellular senescence, genetic predisposition, telomere shortening, oxidative stress, hormonal changes, metabolic processes, and immune system decline, as pivotal contributors to intrinsic aging. External factors, including UV radiation, pollution, lifestyle choices (diet, smoking, alcohol consumption, and sleep patterns), and skincare practices, significantly influence extrinsic skin aging. The interplay between these factors accelerates aging processes, leading to various clinical manifestations like wrinkles, loss of skin elasticity, pigmentation changes, and texture alterations.
    CONCLUSION: A comprehensive understanding of both extrinsic and intrinsic factors contributing to skin aging is essential for developing effective prevention and intervention strategies. The insights gained from this review highlight the importance of a multifaceted approach, incorporating lifestyle modifications, advanced skincare routines, and emerging therapeutic technologies, to mitigate the effects of aging and promote healthier, more resilient skin.
    Keywords:  biological mechanisms; environmental factors; extrinsic aging; intrinsic aging; skin aging
    DOI:  https://doi.org/10.1111/jocd.16688
  8. Biomolecules. 2024 Nov 12. pii: 1436. [Epub ahead of print]14(11):
    Organoids as Tools for Investigating Skin Aging: Mechanisms, Applications, and Insights.
    Xin-Yu Wang, Qian-Nan Jia, Jun Li, He-Yi Zheng.
      Organoids have emerged as transformative tools in biomedical research, renowned for their ability to replicate the complexity construct of human tissues. Skin aging is a multifaceted biological process, influenced by both intrinsic factors and extrinsic factors. Traditional models for studying skin aging often fall short in capturing the intricate dynamics of human skin. In contrast, skin organoids offer a more physiologically relevant system, reflecting the structural and functional characteristics of native skin. These characteristics make skin organoids highly suitable for studying the mechanisms of skin aging, identifying novel therapeutic targets, and testing anti-aging interventions. Despite their promise, challenges such as limited scalability, reproducibility, and ethical considerations remain. Addressing these hurdles through interdisciplinary research and technological advancements will be essential to maximizing the potential of skin organoids for dermatological research and personalized anti-aging therapies.
    Keywords:  aging skin equivalent; aging skin organoid; in vitro skin models; skin aging; skin organoid
    DOI:  https://doi.org/10.3390/biom14111436
  9. Antioxidants (Basel). 2024 Oct 31. pii: 1337. [Epub ahead of print]13(11):
    Senataxin Attenuates DNA Damage Response Activation and Suppresses Senescence.
    Mingyang Li, Genbao Shao.
      Oxidative stress, driven by reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), induces DNA double-strand breaks (DSBs) that compromise genomic integrity. The DNA Damage Response (DDR), primarily mediated by ATM and ATR kinases, is crucial for recognizing and repairing DSBs. Senataxin (SETX), a DNA/RNA helicase, is critical in resolving R-loops, with mutations in SETX associated with neurodegenerative diseases. This study uncovers a novel function of senataxin in modulating DDR and its impact on cellular senescence. Senataxin is shown to be crucial not only for DSB repair but also for determining cell fate under oxidative stress. SETX knockout cells show impaired DSB repair and prolonged ATM/ATR signaling detected by Western blotting, leading to increased senescence, as indicated by elevated β-galactosidase activity following H2O2 exposure and I-PpoI-induced DSBs. Wild-type cells exhibit higher apoptosis levels compared to SETX knockout cells under H2O2 treatment, suggesting that senataxin promotes apoptosis over senescence in oxidative stress. This indicates that senataxin plays a protective role against the accumulation of senescent cells, potentially mitigating age-related cellular decline and neurodegenerative disease progression. These findings highlight senataxin as a critical mediator in DDR pathways and a potential therapeutic target for conditions where cellular senescence contributes to disease pathology.
    Keywords:  DNA damage response; DNA double-strand break repair; SETX; apoptosis; oxidative stress; senataxin; senescence
    DOI:  https://doi.org/10.3390/antiox13111337
  10. Ageing Res Rev. 2024 Nov 23. pii: S1568-1637(24)00403-3. [Epub ahead of print] 102585
    Fecal Microbiota Transplantation, a tool to transfer healthy longevity.
    Marta G Novelle, Beatriz Naranjo, Juan L López-Cánovas, Alberto Díaz-Ruiz.
      The complex gut microbiome influences host aging and plays an important role in the manifestation of age-related diseases. Restoring a healthy gut microbiome via Fecal Microbiota Transplantation (FMT) is receiving extensive consideration to therapeutically transfer healthy longevity. Herein, we comprehensively review the benefits of gut microbial rejuvenation - via FMT - to promote healthy aging, with few studies documenting life length properties. This review explores how preconditioning donors via standard - lifestyle and pharmacological - antiaging interventions reshape gut microbiome, with the resulting benefits being also FMT-transferable. Finally, we expose the current clinical uses of FMT in the context of aging therapy and address FMT challenges - regulatory landscape, protocol standardization, and health risks - that require refinement to effectively utilize microbiome interventions in the elderly.
    Keywords:  FMT-concerns; aging; fecal microbiota transplantation; gut-microbiome; longevity
    DOI:  https://doi.org/10.1016/j.arr.2024.102585
  11. Biochim Biophys Acta Mol Basis Dis. 2024 Nov 22. pii: S0925-4439(24)00577-5. [Epub ahead of print]1871(2): 167583
    Ca2+/calmodulin signaling in organismal aging and cellular senescence: Impact on human diseases.
    Martin W Berchtold, Antonio Villalobo.
      Molecular mechanisms of aging processes at the level of organisms and cells are in the focus of a large number of research laboratories. This research culminated in recent breakthroughs, which contributed to the better understanding of the natural aging process and aging associated malfunctions leading to age-related diseases. Ca2+ in connection with its master intracellular sensor protein calmodulin (CaM) regulates a plethora of crucial cellular processes orchestrating a wide range of signaling processes. This review focuses on the involvement of Ca2+/CaM in cellular mechanisms, which are associated with normal aging, as well as playing a role in the development of diseases connected with signaling processes during aging. We specifically highlight processes that involve inactivation of proteins, which take part in Ca2+/CaM regulatory systems by oxygen or nitrogen free radical species, during organismal aging and cellular senescence. As examples of organs where aging processes have recently been investigated, we chose to review the literature on molecular aging processes with involvement of Ca2+/CaM in heart and neuronal diseases, as well as in cancer and metabolic diseases, all deeply affected by aging. In addition, this article focuses on cellular senescence, a mechanism that may contribute to aging processes and therefore has been proposed as a target to interfere with the progression of age-associated diseases.
    Keywords:  Aging; Calmodulin; Cellular senescence; Disease; Neurodegeneration
    DOI:  https://doi.org/10.1016/j.bbadis.2024.167583
  12. Mar Drugs. 2024 Nov 04. pii: 496. [Epub ahead of print]22(11):
    Marine-Derived Bioactive Ingredients in Functional Foods for Aging: Nutritional and Therapeutic Perspectives.
    Youngji Han, Dong Hyun Kim, Seung Pil Pack.
      Aging is closely linked to various health challenges, including cardiovascular disease, metabolic disorders, and neurodegenerative conditions. This study emphasizes the critical role of bioactive compounds derived from marine sources, such as antioxidants, omega-3 fatty acids, vitamins, minerals, and polysaccharides, in addressing oxidative stress, inflammation, and metabolic disorders closely related to aging. Incorporating these materials into functional foods not only provides essential nutrients but also delivers therapeutic effects, thereby promoting healthy aging and mitigating age-related diseases. The growth of the global anti-aging market, particularly in North America, Europe, and Asia, underscores the significance of this study. This review systematically analyzes the current research, identifying key bioactive compounds, their mechanisms of action, and their potential health benefits, thus highlighting the broad applicability of marine-derived bioactive compounds to enhancing healthy aging and improving the quality of life of aging populations.
    Keywords:  aging; anti-aging; functional food; marine-derived bioactive compounds
    DOI:  https://doi.org/10.3390/md22110496
  13. Biomedicines. 2024 Nov 07. pii: 2540. [Epub ahead of print]12(11):
    The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies.
    Vharoon Sharma Nunkoo, Alexander Cristian, Anamaria Jurcau, Razvan Gabriel Diaconu, Maria Carolina Jurcau.
      The impressive achievements made in the last century in extending the lifespan have led to a significant growth rate of elderly individuals in populations across the world and an exponential increase in the incidence of age-related conditions such as cardiovascular diseases, diabetes mellitus type 2, and neurodegenerative diseases. To date, geroscientists have identified 12 hallmarks of aging (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, impaired macroautophagy, mitochondrial dysfunction, impaired nutrient sensing, cellular senescence, stem cell exhaustion, defective intercellular communication, chronic inflammation, and gut dysbiosis), intricately linked among each other, which can be targeted with senolytic or senomorphic drugs, as well as with more aggressive approaches such as cell-based therapies. To date, side effects seriously limit the use of these drugs. However, since rejuvenation is a dream of mankind, future research is expected to improve the tolerability of the available drugs and highlight novel strategies. In the meantime, the medical community, healthcare providers, and society should decide when to start these treatments and how to tailor them individually.
    Keywords:  aging; hallmarks of aging; neurodegeneration; rejuvenation; senolytics; senomorphics
    DOI:  https://doi.org/10.3390/biomedicines12112540
  14. J Transl Med. 2024 Nov 28. 22(1): 1080
    Inhibition of the E3 ligase UBR5 stabilizes TERT and protects vascular organoids from oxidative stress.
    Haijing Zhao, Nian Cao, Qi Liu, Yingyue Zhang, Rui Jin, Huiying Lai, Li Zheng, Honghong Zhang, Yue Zhu, Yuhan Ma, Zengao Yang, Zhengfeng Wu, Weini Li, Yuqi Liu, Long Cheng, Yundai Chen.
       BACKGROUND: Excessive oxidative stress is known to cause endothelial dysfunction and drive cardiovascular diseases (CVD). While telomerase reverse transcriptase (TERT) shows protective effects against oxidative stress in rodents and is associated to human flow-mediated dilation in CVD, its regulatory mechanisms in human vascular systems under pathological oxidative stress require further investigation.
    METHODS: Human induced pluripotent stem cells (hiPSCs) were used to create vascular organoids (VOs). These VOs and human umbilical vein endothelial cells (HUVECs) were subjected to oxidative stress through both hydrogen peroxide (H2O2) and oxidized low-density lipoprotein (oxLDL) models. The effects of TERT overexpression by inhibition of the ubiquitin protein ligase E3 component N-recognin 5 (UBR5) on reactive oxygen species (ROS)-induced vascular injury and cellular senescence were assessed using neovascular sprouting assays, senescence-associated β-galactosidase (SA-β-Gal) staining, and senescence-associated secretory phenotype (SASP) assays.
    RESULTS: ROS significantly impaired VO development and endothelial progenitor cell (EPC) angiogenesis, evidenced by reduced neovascular sprouting and increased senescence markers, including elevated SA-β-Gal activity and SASP-related cytokine levels. Overexpression of TERT counteracted these effects, restoring VO development and EPC function. Immunoprecipitation-mass spectrometry identified UBR5 as a critical TERT regulator, facilitating its degradation. Inhibition of UBR5 stabilized TERT, improving VO angiogenic capacity, and reducing SA-β-Gal activity and SASP cytokine levels.
    CONCLUSIONS: Inhibiting UBR5 stabilizes TERT, which preserves EPC angiogenic capacity, reduces VO impairment, and delays endothelial cell senescence under oxidative stress. These findings highlight the potential of targeting UBR5 to enhance vascular health in oxidative stress-related conditions.
    Keywords:  Oxidative stress; Senescence; TERT; UBR5; Vascular organoids
    DOI:  https://doi.org/10.1186/s12967-024-05887-0
  15. Antioxidants (Basel). 2024 Oct 23. pii: 1282. [Epub ahead of print]13(11):
    Anti-Inflammatory and Autophagy Activation Effects of 7-Methylsulfonylheptyl Isothiocyanate Could Suppress Skin Aging: In Vitro Evidence.
    Yeong Hee Cho, Jung Eun Park.
      Skin inflammation, characterized by redness, swelling, and discomfort, is exacerbated by oxidative stress, where compounds like 7-methylsulfonylheptyl isothiocyanate (7-MSI) from cruciferous plants exhibit promising antioxidant and anti-inflammatory properties, though their effects on skin aging and underlying mechanisms involving the NLRP3 inflammasome and autophagy are not fully elucidated. NLRP3 is a crucial inflammasome involved in regulating inflammatory responses, and our study addresses its activation and associated physiological effects. Using biochemical assays such as ELISA, RT-qPCR, Western blotting, confocal microscopy, and RNA interference, we evaluated 7-MSI's impact on cytokine production, protein expression, and genetic regulation in Raw 264.7 and RAW-ASC cells. 7-MSI significantly reduced TNF-α, IL-1β, IL-6, COX-2, and PGE transcription levels in LPS-stimulated Raw 264.7 cells, indicating potent anti-inflammatory effects. It also inhibited NF-κB signaling and NLRP3 inflammasome activity, demonstrating its role in preventing the nuclear translocation of NF-κB and reducing caspase-1 and IL-1β production. In terms of autophagy, 7-MSI enhanced the expression of Beclin-1, LC3, and Atg12 while reducing phospho-mTOR levels, suggesting an activation of autophagy. Moreover, it effectively decreased ROS production induced by LPS. The interaction between autophagy and inflammasome regulation was further confirmed through experiments showing that interference with autophagy-related genes altered the effects of 7-MSI on cytokine production. Collectively, this study demonstrates that 7-MSI promotes autophagy, including ROS removal, and to suppress inflammation, we suggest the potential use of 7-MSI as a skin care and disease treatment agent.
    Keywords:  7-MSI; NLRP3; autophagy; inflammation; skin aging
    DOI:  https://doi.org/10.3390/antiox13111282
  16. Nat Rev Mol Cell Biol. 2024 Nov 29.
    Telomere function and regulation from mouse models to human ageing and disease.
    Corey Jones-Weinert, Laura Mainz, Jan Karlseder.
      Telomeres protect the ends of chromosomes but shorten following cell division in the absence of telomerase activity. When telomeres become critically short or damaged, a DNA damage response is activated. Telomeres then become dysfunctional and trigger cellular senescence or death. Telomere shortening occurs with ageing and may contribute to associated maladies such as infertility, neurodegeneration, cancer, lung dysfunction and haematopoiesis disorders. Telomere dysfunction (sometimes without shortening) is associated with various diseases, known as telomere biology disorders (also known as telomeropathies). Telomere biology disorders include dyskeratosis congenita, Høyeraal-Hreidarsson syndrome, Coats plus syndrome and Revesz syndrome. Although mouse models have been invaluable in advancing telomere research, full recapitulation of human telomere-related diseases in mice has been challenging, owing to key differences between the species. In this Review, we discuss telomere protection, maintenance and damage. We highlight the differences between human and mouse telomere biology that may contribute to discrepancies between human diseases and mouse models. Finally, we discuss recent efforts to generate new 'humanized' mouse models to better model human telomere biology. A better understanding of the limitations of mouse telomere models will pave the road for more human-like models and further our understanding of telomere biology disorders, which will contribute towards the development of new therapies.
    DOI:  https://doi.org/10.1038/s41580-024-00800-5
  17. Bioengineering (Basel). 2024 Oct 31. pii: 1100. [Epub ahead of print]11(11):
    Optimization and Implication of Adipose-Derived Stem Cells in Craniofacial Bone Regeneration and Repair.
    Cong Gu, Qinghuang Tang, Liwen Li, YiPing Chen.
      Adipose-derived stem cells (ADSCs) have emerged as a promising resource for craniofacial bone regeneration due to their high abundance and easy accessibility, significant osteogenic potential, versatile applications, and potential for personalized medicine, which underscore their importance in this field. This article reviews the current progress of preclinical studies that describe the careful selection of specific ADSC subpopulations, key signaling pathways involved, and usage of various strategies to enhance the osteogenic potential of ADSCs. Additionally, clinical case reports regarding the application of ADSCs in the repair of calvarial defects, cranio-maxillofacial defects, and alveolar bone defects are also discussed.
    Keywords:  ADSCs; adipose-derived stem cells; craniofacial bone regeneration
    DOI:  https://doi.org/10.3390/bioengineering11111100
  18. Nucleic Acids Res. 2024 Nov 28. pii: gkae1144. [Epub ahead of print]
    DNA sequence and lesion-dependent mitochondrial transcription factor A (TFAM)-DNA-binding modulates DNA repair activities and products.
    Kathleen Urrutia, Yu Hsuan Chen, Jin Tang, Ta I Hung, Guodong Zhang, Wenyan Xu, Wenxin Zhao, Dylan Tonthat, Chia-En A Chang, Linlin Zhao.
      Mitochondrial DNA (mtDNA) is indispensable for mitochondrial function and is maintained by DNA repair, turnover, mitochondrial dynamics and mitophagy, along with the inherent redundancy of mtDNA. Base excision repair (BER) is a major DNA repair mechanism in mammalian mitochondria. Mitochondrial BER enzymes are implicated in mtDNA-mediated immune response and inflammation. mtDNA is organized into mitochondrial nucleoids by mitochondrial transcription factor A (TFAM). The regulation of DNA repair activities by TFAM-DNA interactions remains understudied. Here, we demonstrate the modulation of DNA repair enzymes by TFAM concentrations, DNA sequences and DNA modifications. Unlike previously reported inhibitory effects, we observed that human uracil-DNA glycosylase 1 (UNG1) and AP endonuclease I (APE1) have optimal activities at specific TFAM/DNA molar ratios. High TFAM/DNA ratios inhibited other enzymes, OGG1 and AAG. In addition, TFAM reduces the accumulation of certain repair intermediates. Molecular dynamics simulations and DNA-binding experiments demonstrate that the presence of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in certain sequence motifs enhances TFAM-DNA binding, partially explaining the inhibition of OGG1 activity. Bioinformatic analysis of published 8-oxodG, dU, and TFAM-footprint maps reveals a correlation between 8-oxodG and TFAM locations in mtDNA. Collectively, these results highlight the complex regulation of mtDNA repair by DNA sequence, TFAM concentrations, lesions and repair enzymes.
    DOI:  https://doi.org/10.1093/nar/gkae1144
  19. Biomolecules. 2024 Nov 13. pii: 1442. [Epub ahead of print]14(11):
    Action-At-A-Distance in DNA Mismatch Repair: Mechanistic Insights and Models for How DNA and Repair Proteins Facilitate Long-Range Communication.
    Bryce W Collingwood, Scott J Witte, Carol M Manhart.
      Many DNA metabolic pathways, including DNA repair, require the transmission of signals across long stretches of DNA or between DNA molecules. Solutions to this signaling challenge involve various mechanisms: protein factors can travel between these sites, loop DNA between sites, or form oligomers that bridge the spatial gaps. This review provides an overview of how these paradigms have been used to explain DNA mismatch repair, which involves several steps that require action-at-a-distance. Here, we describe these models in detail and how current data fit into these descriptions. We also outline regulation steps that remain unanswered in how the action is communicated across long distances along a DNA contour in DNA mismatch repair.
    Keywords:  DNA mismatch repair; DNA polymerase δ; DNA repair; EXO1; MutL; MutS
    DOI:  https://doi.org/10.3390/biom14111442
  20. Nutrients. 2024 Nov 08. pii: 3830. [Epub ahead of print]16(22):
    Immune Alterations with Aging: Mechanisms and Intervention Strategies.
    Weiru Yu, Yifei Yu, Siyuan Sun, Chenxu Lu, Jianan Zhai, Yumei Lei, Feirong Bai, Ran Wang, Juan Chen.
      Aging is the result of a complex interplay of physical, environmental, and social factors, leading to an increased prevalence of chronic age-related diseases that burden health and social care systems. As the global population ages, it is crucial to understand the aged immune system, which undergoes declines in both innate and adaptive immunity. This immune decline exacerbates the aging process, creating a feedback loop that accelerates the onset of diseases, including infectious diseases, autoimmune disorders, and cancer. Intervention strategies, including dietary adjustments, pharmacological treatments, and immunomodulatory therapies, represent promising approaches to counteract immunosenescence. These interventions aim to enhance immune function by improving the activity and interactions of aging-affected immune cells, or by modulating inflammatory responses through the suppression of excessive cytokine secretion and inflammatory pathway activation. Such strategies have the potential to restore immune homeostasis and mitigate age-related inflammation, thus reducing the risk of chronic diseases linked to aging. In summary, this review provides insights into the effects and underlying mechanisms of immunosenescence, as well as its potential interventions, with particular emphasis on the relationship between aging, immunity, and nutritional factors.
    Keywords:  aging; diet intervention; immune system; immunosenescence; immunotherapy
    DOI:  https://doi.org/10.3390/nu16223830
  21. Food Res Int. 2024 Dec;pii: S0963-9969(24)01213-4. [Epub ahead of print]197(Pt 1): 115143
    High exposure to carrageenan in young mice may impair behavior, immunity, redox and inflammatory states throughout the aging process.
    Judith Félix, Alicia Bellanco, Estefanía Díaz-Del Cerro, M Carmen Martínez-Cuesta, Teresa Requena, Mónica De la Fuente.
      The rate of aging can be determined, among other factors, by the diet during childhood and adolescence. Many additives are currently added to food, including carrageenan (E-407), a thickener derived from red algae. Although the acceptable daily intake for carrageenan is periodically re-evaluated, children show the highest levels of exposure with unknown potential effects on the aging process and longevity. Therefore, the aim of the present study is to know the effects in young mice of carrageenan intake, at the maximum level exposure scenario surveyed in children, on the homeostatic (nervous and immune) systems, the redox-inflammatory state and the repercussion that this may have on the aging and longevity of the animals. Swiss mice of 2 months of age (equivalent to 8 years old children) were used and 4 experimental groups were created (N = 10 animals/group): females and males that ingested carrageenan (540 mg/kg of κ-carrageenan in 200 μL of drinking water by pipette tip administration) and control females and males that took 200 μL of water, daily for 15 days. After that time, a battery of behavioral tests was performed, and peritoneal leukocytes were extracted to assess different immune functions and their redox and inflammatory state. These tests were repeated when the mice reached adulthood (7 months) and old age (18 months). Fecal microbiota was analyzed at the same sampling times. The results showed that animals that ingested carrageenan presented elevated levels of anxiety, impaired immune function and increased oxidative-inflammatory stress, with these effects extending into adulthood and old age and leading to reduced longevity in these mice. Overall, observed microbiota changes were related more to the aging process than the carrageenan intake. In conclusion, the exposure to high doses of the food additive carrageenan in childhood may contribute to an impairment of homeostasis, and consequently of health, with an increased oxidative-inflammatory stress, which implies an accelerated aging process, leading to a lower longevity.
    Keywords:  Behavior; Carrageenan; Food additive; Immunity; Inflammation; Longevity; Microbiota; Oxidation
    DOI:  https://doi.org/10.1016/j.foodres.2024.115143
  22. Adv Biol (Weinh). 2024 Nov 27. e2400334
    Age-Related ECM Stiffness Mediates TRAIL Activation in Muscle Stem Cell Differentiation.
    Amira A Alakhdar, Sruthi Sivakumar, Rylee M Kopchak, Allison N Hunter, Fabrisia Ambrosio, Newell R Washburn.
      The stiffening of the extracellular matrix (ECM) with age hinders muscle regeneration by causing intrinsic muscle stem cell (MuSC) dysfunction through a poorly understood mechanism. Here, the study aims to study those age-related molecular changes in the differentiation of MuSCs due to age and/or stiffness. Hence, young and aged MuSCs are seeded onto substrates engineered to mimic a soft and stiff ECM microenvironment to study those molecular changes using single-cell RNA sequencing (scRNA). The trajectory of scRNA data of the MuSCs under four different conditions undergoing differentiation is analyzed as well as the active molecular pathways and transcription factors driving those differentiation fates. Data revealed the presence of a branching point within the trajectory leading to the emergence of an age-related fibroblastic population characterized by activation of the TNF-related apoptosis-inducing ligand (TRAIL) pathway, which is significantly activated in aged cells cultured on stiff substrates. Next, using the collagen cross-linking inhibitor β-aminopropionitrile (BAPN) in vivo, the study elucidates stiffness changes on TRAIL downstream apoptotic targets (caspase 8 and caspase 3) using immunostaining. TRAIL activity is significantly inhibited by BAPN in aged animals, indicating a complex mechanism of age-related declines in muscle function through inflammatory and apoptotic mediators.
    Keywords:  TRAIL; aging; extracellular matrix (ECM); fibrogenic conversion; fibrosis; muscle regeneration; muscle stem cells; scRNA analysis; stiffness
    DOI:  https://doi.org/10.1002/adbi.202400334
  23. J Ginseng Res. 2024 Nov;48(6): 525-534
    Ginseng and ginseng byproducts for skincare and skin health.
    Ji-Hun Kim, Rami Lee, Sung-Hee Hwang, Sun-Hye Choi, Jong-Hoon Kim, Ik-Hyun Cho, Jeong Ik Lee, Seung-Yeol Nah.
      Ginseng is a traditional herbal medicine with a long history of use for the prevention and/or treatment of various diseases. Ginseng is used worldwide as a functional food to maintain human health. In addition, ginseng has been used as a raw ingredient in cosmetics with various applications, ranging from skin toning to anti-aging. Some cosmetic products contain ginseng extracts from Korea and other countries, as it is thought that ginseng can also exert beneficial effects on human skin. However, it remains unclear which ginseng component(s) could be the main active compound that directly contributes to skin health and/or prevents skin aging. It is also important to understand the mechanisms by which the ginseng component(s) exert their effects on the skin and skin health. This review describes recent in vitro and in vivo studies involving ginseng extracts, ginseng ingredients, and ginseng byproducts for skincare and skin health and discusses emerging evidence that ginsenosides, gintonin, and ginseng byproducts could be novel candidates for skincare and skin health applications ranging from anti-aging to the treatment of skin diseases such as atopic dermatitis and hypertrophic scars and keloids. The mechanisms underlying the beneficial effects of ginseng components and byproducts on skin health are discussed. In addition, this review shows how ginseng components, such as gintonin, a newly identified ginseng component, might contribute to skin health and skin disease when used as a supplementary ingredient in cosmetics and further proposes a novel combination in cosmetic products containing both ginsenosides and gintonin.
    Keywords:  Cosmetic ingredients; Cosmetics; Ginseng; Ginsenosides; Gintonin; Lysophosphatidic acid
    DOI:  https://doi.org/10.1016/j.jgr.2024.09.006
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