RE: News aus der Forschung - 9

High-dimensional Ageome Representations of Biological Aging across Functional Modules

Zitat

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In this study, we challenge the paradigm that aging can be sufficiently described with a single biological age estimate. We describe Ageome, a computational framework for measuring the epigenetic age of thousands of molecular pathways simultaneously in mice and humans. Ageome is based on the premise that an organism's overall biological age can be approximated by the collective ages of its functional modules, which may age at different rates and have different biological ages. We show that, unlike conventional clocks, Ageome provides a high-dimensional representation of biological aging across cellular functions, enabling comprehensive assessment of aging dynamics within an individual, in a population, and across species. Application of Ageome to longevity intervention models revealed distinct patterns of pathway-specific age deceleration. Notably, cell reprogramming, while rejuvenating cells, also accelerated aging of some functional modules. When applied to human cohorts, Ageome demonstrated heterogeneity in predictive power for mortality risk, and some modules showed better performance in predicting the onset of age-related diseases, especially cancer, compared to existing clocks. Together, the Ageome framework offers a comprehensive and interpretable approach for assessing aging, providing insights into mechanisms and targets for intervention.

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https://www.biorxiv.org/content/10.1101/2024.09.17.613599v1

Zitat von Illuminatus im Beitrag #200

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Ich ahne es 🐒🐒
The Bad Touch

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Zitat von Prometheus im Beitrag #202

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Kommentar Prometheus: Solche Master-Regulatoren besser zu identifizieren wäre sicherlich hilfreich - gerade weil sich z.B. eine heterochrome Parabiose am Menschen nicht umsetzen lässt

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Zitat von Prometheus im Beitrag #202

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Kommentar Prometheus: So ein "Ageom" ist natürlich ein Stück näher am "wahren" biologischen Alter. Hilfreich könnte es sein, damit die Funktionsmodule zu identifizieren, die am kritischsten sind.

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Blood boffins build billions of nanobots to battle brain aneurysms without surgery

Zitat

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An international team of scientists has developed a drug delivery system that could one day treat human brain aneurysms in a way without the need for traditional surgery.

The team said it built billions of tiny simple magnetic nanorobots - each 300nm in diameter, or about a twentieth the width of a human red blood cell - that contain clotting medications. After injecting several hundred billion of these into a rabbit's artery, the scientists used magnets and medical imaging technology to cause the bots to cluster together inside an aneurysm, according to the boffins.

The bots were then heated to their melting point. The process released a naturally occurring blood-clotting protein to prevent or stop the aneurysm bleeding into the brain, the researchers noted.

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https://www.theregister.com/2024/09/07/n...rain_aneurysms/

Scientists investigate a potential anti-aging drug that could preserve proteasomes and autophagy systems

Zitat

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The results were quite promising, as Prof. Hyun remarks, "Inhibiting the activity of ubiquitin specific peptidase 14 (USP14), a component of the proteasome complex, with IU1 enhanced not only proteasome activity but also autophagy activity simultaneously. We demonstrated that this synergistic mechanism could improve age-related muscle weakness in fruit flies and extend their lifespan." Worth noting that similar results were obtained in human cells.

These findings have important ramifications, especially regarding advances in anti-aging therapy. "Reduced protein homeostasis is a major characteristic of degenerative diseases such as Alzheimer's and Parkinson's disease. The results of our study might lay the groundwork for the development of treatments for various age-related diseases," says Prof. Hyun.

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https://medicalxpress.com/news/2024-09-s...aging-drug.html

Das Paper:

Pharmacological inhibition of USP14 delays proteostasis-associated aging in a proteasome-dependent but foxo-independent manner
https://www.tandfonline.com/doi/full/10....27.2024.2389607

Weiß jemand, was dieses IU1 genau ist?

Zitat von Prometheus im Beitrag #206

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Zitat von version2 im Beitrag #205

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Weiß jemand, was dieses IU1 genau ist?

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Hier: https://bpsbioscience.com/iu1-27227

In einer Studie von 2010 das erste mal gefunden:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939003/

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Systemic extracellular acidification is a hallmark of aging
https://www.biorxiv.org/content/10.1101/2024.09.24.614672v1

Replicative Endothelial Cell Senescence May Lead to Endothelial Dysfunction by Increasing the BH2/BH4 Ratio Induced by Oxidative Stress, Reducing BH4 Availability, and Decreasing the Expression of eNOS
https://www.mdpi.com/1422-0067/25/18/9890

Zitat von Speedy im Beitrag #209

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Replicative Endothelial Cell Senescence May Lead to Endothelial Dysfunction by Increasing the BH2/BH4 Ratio Induced by Oxidative Stress, Reducing BH4 Availability, and Decreasing the Expression of eNOS
https://www.mdpi.com/1422-0067/25/18/9890

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The impact of short-lived controls on the interpretation of lifespan experiments and progress in geroscience – through the lens of the “900-day rule”

Zitat

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• Caloric restriction works better in short-lived strains
• Most other longevity treatments work better in short-lived strains
• This is explained by both biological and statistical effects (“regression to the mean”)
• Usage of healthy, long-lived mouse strains will lead to more robust results
• Mouse lifespans in experiments improved over the last decades, stagnating now

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https://www.sciencedirect.com/science/ar...568163724003301

GLP-1 programs the neurovascular landscape
https://www.cell.com/cell-metabolism/ful...4131(24)00367-X

Unlocking new regenerative pathways in iPS cell-derived epicardium for cardiac repair
https://www.cira.kyoto-u.ac.jp/e/pressre...z1-wVB7__r1lzBg

CRISPR–Cas9 screens reveal regulators of ageing in neural stem cells
https://www.nature.com/articles/s41586-0...Jet8mJnoHT502Sw

New Molecule Mimics Exercise and Fasting Effects
https://neurosciencenews.com/lake-exerci...EuR9q0njS5NStrQ

Zitat von Speedy im Beitrag #216

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New Molecule Mimics Exercise and Fasting Effects
https://neurosciencenews.com/lake-exerci...EuR9q0njS5NStrQ

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Mosaic Regulation of Stress Pathways Underlies Senescent Cell Heterogeneity

Zitat

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Cellular senescence (CS) and quiescence (CQ) are stress responses characterised by persistent and reversible cell cycle arrest, respectively. These phenotypes are heterogeneous, dependent on the cell type arrested and the insult inciting arrest. Because a universal biomarker for CS has yet to be identified, combinations of senescence-associated biomarkers linked to various biological stress responses including lysosomal activity (β-galactosidase staining), inflammation (senescence-associated secretory phenotypes, SASPs), and apoptosis (senescent cell anti-apoptotic pathways) are used to identify senescent cells. Using in vitro human bulk RNA-seq datasets, we find that senescent states enrich for various stress responses in a cell-type, temporal, and insult-dependent manner. We further demonstrate that various gene signatures used to identify senescent cells in the literature also enrich for stress responses, and are inadequate for universally and exclusively identifying senescent samples. Genes regulating stress responses - including transcription factors and genes controlling chromatin accessibility - are contextually differentially expressed, along with key enzymes involved in metabolism across arrest phenotypes. Additionally, significant numbers of SASP proteins can be predicted from senescent cell transcriptomes and also heterogeneously enrich for various stress responses in a context-dependent manner. We propose that 'senescence' cannot be meaningfully defined due to the lack of underlying preserved biology across senescent states, and CS is instead a mosaic of stress-induced phenotypes regulated by various factors, including metabolism, TFs, and chromatin accessibility. We introduce the concept of Stress Response Modules, clusters of genes modulating stress responses, and present a new model of CS and CQ induction conceptualised as the differential activation of these clusters.

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Kommentar: Preprint. Zudem gibt es ein Competing Interest Statement.

So kann microRNA bei der Behandlung schwerer Krankheiten helfen

Der Medizin-Nobelpreis geht in diesem Jahr an zwei US-Forscher für die Entdeckung von microRNA. Diese Moleküle stehen bei einer ganzen Reihe von Krankheiten an der Schwelle zur Anwendung

https://www.geo.de/wissen/forschung-und-...et-newtab-de-de

#219 Da darf man gespannt sein, was für verjüngende microRNAs noch entdeckt werden.

Eating less can lead to a longer life: massive study in mice shows why

Zitat

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What mattered most for lengthening lifespan were traits related to immune health and red-blood-cell function. Also key was overall resilience, presumably encoded in the animals’ genes, to the stress of reduced food intake.

“The intervention is a stressor,” Churchill explains. The most-resilient animals lost the least weight, maintained immune function and lived longer.

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https://www.nature.com/articles/d41586-024-03277-6

World-first therapy using donor cells sends autoimmune diseases into remission
https://www.nature.com/articles/d41586-0...t=ap_9nzmfdvuqu

Exosomes Break Rat Lifespan Record
https://www.lifespan.io/news/exosomes-br...ifespan-record/

The brain–body energy conservation model of aging
https://www.nature.com/articles/s43587-024-00716-x

Linking DNA damage and senescence to gestation period and lifespan in placental mammals
https://www.frontiersin.org/journals/cel...I0S0OEiLIj065ag

Hydrogen sulfide mitigates mitochondrial dysfunction and cellular senescence in diabetic patients: Potential therapeutic applications
https://www.sciencedirect.com/science/ar...5562?via%3Dihub