RE: News aus der Forschung - 11

Mesenchymal Stem Cells Rejuvenate Aged Mice

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In a new study, the researchers administered human umbilical cord-derived mesenchymal stem cells (HUCMSCs) to aged mice and observed reduced degeneration in multiple organs, changes to microbial composition, metabolic alterations, improvements in behavior and ability, and reduced fearfulness [1].

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https://www.lifespan.io/news/mesenchymal...nate-aged-mice/

Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging
https://www.sciencedirect.com/science/ar...XKMURn4B0b8esXg

Saturated Fats: Time to Assess Their Beneficial Role in a Healthful Diet
https://www.mdpi.com/2674-0311/3/4/33

Accumulation of advanced oxidation protein products promotes age-related decline of type H vessels in bone

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Type H vessels have been proven to couple angiogenesis and osteogenesis. The decline of type H vessels contributes to bone loss in the aging process. Aging is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, whether AOPP accumulation is involved in age-related decline of type H vessels is unclear. Here, we show that the increase of AOPP levels in plasma and bone were correlated with the decline of type H vessels and loss of bone mass in old mice. Exposure of microvascular endothelial cells to AOPPs significantly inhibited cell proliferation, migration, and tube formation, increased NADPH oxidase activity and excessive reactive oxygen species generation, upregulated the expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1, and eventually impaired angiogenesis, which was alleviated by redox modulator N-acetylcysteine and NADPH oxidase inhibitor apocynin. Furthermore, reduced AOPP accumulation by NAC treatment was able to alleviate significantly the decline of type H vessels, bone mass loss and deterioration of bone microstructure in old mice. Collectively, these findings suggest that AOPPs accumulation contributes to the decline of type H vessels in the aging process, and illuminate a novel potential mechanism underlying age-related bone loss.

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https://academic.oup.com/biomedgerontolo...glae271/7882886

Human skin rejuvenation via mRNA

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Aging is characterized by a gradual decline in function, partly due to accumulated molecular damage. Human skin undergoes both chronological aging and environmental degradation, particularly UV-induced photoaging. Detrimental structural and physiological changes caused by aging include epidermal thinning due to stem cell depletion and dermal atrophy associated with decreased collagen production. Here, we present a comprehensive single-cell atlas of skin aging, analyzing samples from young, middle-aged, and elderly individuals, including both sun-exposed and sun-protected areas. This atlas reveals age-related cellular composition and function changes across various skin cell types, including epidermal stem cells, fibroblasts, hair follicles, and endothelial cells. Using our atlas, we have identified basal stem cells as a highly variable population across aging, more so than other skin cell populations such as fibroblasts. In basal stem cells, we identified ATF3 as a novel regulator of skin aging. ATF3 is a transcriptional factor for genes involved in the aging process, with its expression reduced by 20% during aging. Based on this discovery, we have developed an innovative mRNA-based treatment to mitigate the effects of skin aging. Cell senescence decreased 25% in skin cells treated with ATF3 mRNA, and we observed an over 20% increase in proliferation in treated basal stem cells. Importantly, we also found crosstalk between keratinocytes and fibroblasts as a critical component of therapeutic interventions, with ATF3 rescue of basal cells significantly enhancing fibroblast collagen production by approximately 200%. We conclude that ATF3-targeted mRNA treatment effectively reverses the effects of skin aging by modulating specific cellular mechanisms, offering a novel, targeted approach to human skin rejuvenation.

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https://www.biorxiv.org/content/10.1101/2024.11.12.623261v1

Danke, interessant.

Phytochemical Characterization and Antibacterial Activity of Carthamus Caeruleus L. Aqueous Extracts: In Vitro and In Silico Molecular Docking Studies

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In order to valorize natural resources and the traditional use of medicinal plants in Algeria, this study exploits the antibacterial effect of Carthamus caeruleus L. Since there are few studies on this plant despite its notable therapeutic potential, this work aims to characterize the chemical composition of Carthamus caeruleus L. leaf and root aqueous extracts and to evaluate their antibacterial activity through an in vitro and in silico studies. Spectrophotometric assays and HPLC results revealed 22 components in the roots and 16 in the leaves. Disc diffusion and microdilution methods were used to study the antibacterial properties against nine standard bacterial strains. The results showed that roots exhibited the best activity on most tested strains. Both extracts were also able to inhibit the growth of Staphylococcus aureus ATCC 25923 and Escherichia coli ATSC 25922. Furthermore, no nucleic acid leakage or membrane damage was detected. However, molecular docking of the molecules indicates that some constituents have significant affinity and stability for DNA gyrase. Gallic acid, luteolin, myricetin, and orientin were found to have the highest score. The molecular docking data suggest, for the first time, that the antibacterial activity may be caused by the inhibition of DNA gyrase.

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https://pubmed.ncbi.nlm.nih.gov/39535731/

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Bacterial DNA gyrase is the target of many antibiotics, including nalidixic acid, novobiocin, albicidin, and ciprofloxacin.

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https://en.wikipedia.org/wiki/DNA_gyrase

Zitat von Methusalem im Beitrag #257

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Danke, interessant.

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Immunsystem wird zum Tumor-Killer: Neue Impfung gegen Hirntomore

Wissenschaftler entwickeln neue Impfungen gegen aggressive Hirntumore. Das Immunsystem wird zum gezielten Tumor-Killer umprogrammiert. Was diese Therapie so revolutionär macht.

https://www.telepolis.de/features/Immuns...e-10039895.html

Hallo Tizian,

die Verbesserung der Immunantwort ist ein Schritt in die richtige Richtung (Nobelpreis 2018), aber bei der neuen Therapieform werden die Immunzellen genetisch verändert: https://idw-online.de/de/news?id=809684&type=semanticsearch .

Viele Grüße und einen schönen Sonntag

Roger

Age-related loss of intestinal barrier integrity plays an integral role in thymic involution and T cell ageing
https://onlinelibrary.wiley.com/doi/full...54YBdL6e5XK--eQ

The emergence of Sox and POU transcription factors predates the origins of animal stem cells
https://www.nature.com/articles/s41467-024-54152-x

Carbamazepin und Calmagit.

A small-molecule screen identifies novel aging modulators by targeting 5-HT/DA signaling pathway
https://onlinelibrary.wiley.com/doi/10.1111/acel.14411

Endogenous mitochondrial NAD(P)H fluorescence can predict lifespan
https://www.nature.com/articles/s42003-024-07243-w

Molecular and genetic insights into human ovarian aging from single-nuclei multi-omics analyses
https://www.nature.com/articles/s43587-024-00762-5

GLP-1 receptor agonists and SGLT2 inhibitors: new anti-aging tools?
https://www.tandfonline.com/doi/full/10.....2433381#d1e295

The soil Mycobacterium sp. promotes health and longevity through different bacteria-derived molecules in Caenorhabditis elegans
https://onlinelibrary.wiley.com/doi/full...HXfJRyxA97X1mRg

Comprehensive single-cell aging atlas of healthy mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer
https://www.nature.com/articles/s43587-024-00751-8

Dysregulation of endogenous retroviruses triggers aging and senescence
https://www.nature.com/articles/s43587-024-00759-0

Slowed epigenetic aging in Olympic champions compared to non-champions
https://link.springer.com/article/10.1007/s11357-024-01440-5

Metabolite signatures of chronological age, aging, survival, and longevity
https://www.cell.com/cell-reports/fullte...kjQYauI6_4D1lAg

β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain

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Ketone bodies, small molecules that provide lipid-derived energy to cells during fasting, have been linked to various mechanisms of brain aging and increased healthy longevity in mice, and other fasting metabolism mechanisms have been linked to proteostasis. These data fill an important puzzle piece in the literature on pathogenic protein clearance under varying metabolic states. Here, we provide a direct molecular mechanism for the regulation of misfolded proteins by ketone bodies and related metabolites. While many factors can affect protein solubility in vitro, we showed that this mechanism is robust and reproducibly not dependent on covalent protein modification, pH, or solute load. Importantly, we reproduced the ex vivo effect in vivo, using a ketone ester to indirectly deliver exogenous R-βHB to the mouse brain via hepatic metabolism to R-βHB and physiological transport of R-βHB into the brain without other exogenous biochemical alterations. R-βHB insolubilization targets that we identified ex vivo strongly overlap with targets found in vivo, supporting the similarity of mechanism between the ex vivo and in vivo systems. We validated the physiological relevance of the mechanism by showing rescue in cell-based and C. elegans models of amyloid-β proteotoxicity. Given that proteostatic mechanisms like autophagy are known to be activated by nutrient deprivation, it is unsurprising that evolutionary pressures would encourage the clearance of pathogenic proteins during ketosis to promote cellular health in organisms seeking additional substrate for ATP production. In this situation, ketone bodies are janitors of damaged proteins, chaperoning away molecular waste so organisms can operate at peak molecular fitness. This mechanism can be leveraged for therapeutic development in aging and NDDs, including via pharmacological approaches for which we provide proof of principle with BH-BD. Understanding the molecular mechanisms of metabolism is an essential aspect of the future of accessible therapeutic interventions in aging and NDDs.

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https://www.cell.com/cell-chemical-biolo...9456(24)00459-8

Zitat von Prometheus im Beitrag #214

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Pro-Aging Metabolic Reprogramming: A Unified Theory of Aging
https://www.sciencedirect.com/science/ar...571X?via%3Dihub

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The dichotomic role of cytokines in aging
https://link.springer.com/article/10.1007/s10522-024-10152-4

Disagreement on foundational principles of biological aging
https://academic.oup.com/pnasnexus/artic...pgae499/7913315

Thermosensory neurons control genetic inheritance through regulation of germline transposons
https://www.biorxiv.org/content/10.1101/2024.12.02.626368v1