Kommentar Prometheus: Eigentlich logisch - Bei der Messung der Epigenetischen Alterung aus einer Blutprobe misst man fast ausschließlich die Leukozyten, also Zellen des Immunsystems. Berücksichtigt man die Komposition der Zellen, lässt sich nicht nur die Messung präzisieren, sondern das kann auch hilfreich sein bei Krankheitsprävention und -Monitoring.
Im Zuge der OSKM-Reprogrammierung tritt bei Mäusen eine Vitamin B12-Depletion auf. Die Supplementierung verbessert die Effizienz der Reprogrammierung.
Kommentar Prometheus: Unklar bleibt, warum Vitamin B12 sinkt. Erhöhter Verbrauch während der Reprogrammierung? Beeinträchtigtes Mikrobiom durch das verwendete Doxycyclin?
die epigenetische Programmierung macht evtl. bei einer Störung des Stoffwechsels keinen Sinn: z.B. vermehrte Bildung von freien Radikalen und daraus resultierende Hemmung des Stoffwechsels (ATP Mangel), erhöhter Kalziumeinstrom in die Zellen infolge fehlender ATPasen (Dr. Kuklinski) und vermehrte Bildung von NO (Vitamin B12 Mangel).
Cells Across the Body Talk to Each Other About Aging
ZitatBiologists discovered that mitochondria in different tissues talk to each other to repair injured cells. When their signal fails, the biological clock starts winding down.
Mehr als interssant! Dieser universelle Altersmechanismus könnte tatsächlich DER gesuchte Code sein!
Die genomweiten Hypomethylierungen als Altersursache haben wir hier jahrelang intensiv thematisiert - allerdings fehlt es an Optionen, das Auftreten der Hypomethylierungen zu verhindern. Der in dem Paper diskutierte Mechanismus, dass sich mit jeder Zellteilung mehr und mehr G4 ansammeln, ist eine plausible Ursache für die Hypomethylierungen.
Und nicht zuletzt liefert dieser Mechanismus möglicherweise einen vergleichsweise einfachen und eleganten Weg, die Alterung zu stoppen: Man bräuchte lediglich eine Überexpression von WRN, BLM und ERCC8. Technologisch gesehen ist das vergleichsweise einfach umzusetzen!
Life span increases in mice when specific brain cells are activated
ZitatA new study from Washington University School of Medicine in St. Louis identifies, in mice, a critical communication pathway connecting the brain and the body’s fat tissue in a feedback loop that appears central to energy production throughout the body. The research suggests that the gradual deterioration of this feedback loop contributes to the increasing health problems that are typical of natural aging.
Lethal Infection of Human ACE2-Transgenic Mice Caused by SARS-CoV-2-related Pangolin Coronavirus GX_P2V(short_3UTR)
ZitatSARS-CoV-2-related pangolin coronavirus GX_P2V(short_3UTR) can cause 100% mortality in human ACE2-transgenic mice, potentially attributable to late-stage brain infection. This underscores a spillover risk of GX_P2V into humans and provides a unique model for understanding the pathogenic mechanisms of SARS-CoV-2-related viruses.
ZitatAbout a year ago, members of the editorial board of Biogerontology were requested to respond to a query by the editor-in-chief of the journal as to what one question within their field of ageing research still needs to be asked and answered. This editorial is inspired by the wide range and variety of questions, ideas, comments and suggestions received in response to that query. The seven knowledge gaps identified in this article are arranged into three main categories: evolutionary aspects of longevity, biological survival and death aspects, and heterogeneity in the progression and phenotype of ageing. This is not an exhaustive and exclusive list, and may be modified and expanded. Implications of these knowledge gaps, especially in the context of ongoing attempts to develop effective interventions in ageing and longevity are also discussed.
Middle-age high normal serum sodium as a risk factor for accelerated biological aging, chronic diseases, and premature mortality
ZitatIt is known that some people age faster than others, some people live into old age disease-free, while others develop age-related chronic diseases. With a rapidly aging population and an emerging chronic diseases epidemic, finding mechanisms and implementing preventive measures that could slow down the aging process has become a new challenge for biomedical research and public health. In mice, lifelong water restriction shortens the lifespan and promotes degenerative changes. Here, we test the hypothesis that optimal hydration may slow down the aging process in humans.
Researchers genetically modify stem cells to evade immunological rejection
Zitat“There has been a lot of excitement for decades around the field of pluripotent stem cells and regenerative medicine,” said principal investigator Deepta Bhattacharya, PhD, a professor in the UArizona College of Medicine – Tucson’s Department of Immunobiology. “What we have learned from the experiences of organ transplantation is that you have to have matched donors, but the person receiving the transplant often still requires lifelong immune suppression, and that means there is increased susceptibility to infections and cancer. We’ve been trying to figure out what it is that you need to do to those stem cells to keep them from getting rejected, and it looks like we have a possible solution.”
To test their hypothesis, Bhattacharya and the research team used CRISPR-Cas9 technology, “genetic scissors” that allow scientists to make precise mutations within the genome at extremely specific locations.
Using human pluripotent stem cells, the team located the specific genes they believed were involved in immune rejection and removed them. Prior research into pluripotent stem cells and immune rejection looked at different parts of the immune system in isolation. Bhattacharya and his colleagues from The New York Stem Cell Foundation Research Institute, St. Jude Children’s Research Hospital and the Washington University School of Medicine opted to test their genetically modified stem cells in a complete and functional immune system.
Kommentar: Schon spannend, aber ob man fremde Stammzellen haben will? Dann doch lieber eines Tages eigene iPSCs, denn wer weiß wie die fremden wirken können?
Zitat von vera8555 im Beitrag #16Aus diesem ellenlangen Text entnehme ich kurz und klar : im Alter viel trinken !!
Epigenetic Mechanisms in Hematologic Aging and Premalignant Conditions
ZitatHematopoietic stem cells (HSCs) are essential for maintaining overall health by continuously generating blood cells throughout an individual’s lifespan. However, as individuals age, the hematopoietic system undergoes significant functional decline, rendering them more susceptible to age-related diseases. Growing research evidence has highlighted the critical role of epigenetic regulation in this age-associated decline. This review aims to provide an overview of the diverse epigenetic mechanisms involved in the regulation of normal HSCs during the aging process and their implications in aging-related diseases. Understanding the intricate interplay of epigenetic mechanisms that contribute to aging-related changes in the hematopoietic system holds great potential for the development of innovative strategies to delay the aging process. In fact, interventions targeting epigenetic modifications have shown promising outcomes in alleviating aging-related phenotypes and extending lifespan in various animal models. Small molecule-based therapies and reprogramming strategies enabling epigenetic rejuvenation have emerged as effective approaches for ameliorating or even reversing aging-related conditions. By acquiring a deeper understanding of these epigenetic mechanisms, it is anticipated that interventions can be devised to prevent or mitigate the rates of hematologic aging and associated diseases later in life. Ultimately, these advancements have the potential to improve overall health and enhance the quality of life in aging individuals.
Amelioration of experimental autoimmune encephalomyelitis by in vivo reprogramming of macrophages using pro-resolving factors
ZitatWe found that injection of the pro-resolutive secretome reduced demyelination and decreased inflammatory cell infiltration in the CNS, notably through the in vivo reprogramming of macrophages at the epigenetic level. Adoptive transfer experiments with in vivo or in vitro reprogrammed macrophages using such pro-resolutive secretome confirmed the stability and transferability of this acquired therapeutic activity.
Re-energizing mitochondria to treat Alzheimer’s disease
ZitatThe researchers hypothesized that if they could supply some of the missing succinate molecules, they might be able to restore energy production—essentially jumpstarting the stalled mitochondrial Krebs cycle. Since succinate does not easily travel in or out of cells, they used an analog that could better pass through nerve cell membranes. The strategy worked, repairing up to three quarters of the synapses that had been lost, while preventing further decline.
“Succinate is not a compound that people can now take as a treatment, but it’s proof-of-principle that you can re-energize the Krebs cycle,” says Lipton. “The beauty of the study is that we were able to show this in living nerve cells derived from Alzheimer’s patients, but we still have to come up with a much better compound in order to develop an effective drug for humans to take.”