News aus der Forschung - 8

Loss of immune cell identity with age inferred from large atlases of single cell transcriptomes

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By analyzing two large atlases of almost 4 million cells, we show that immune-senescence involves a gradual loss of cellular identity, reflecting increased cellular heterogeneity, for effector, and cytotoxic immune cells.

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https://pubmed.ncbi.nlm.nih.gov/39143696/

Newly discovered protein stops DNA damage

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The researchers found the protein—called DdrC (for DNA Damage Repair Protein C)—in a fairly common bacterium called Deinococcus radiodurans (D. radiodurans), which has the decidedly uncommon ability to survive conditions that damage DNA—for example, 5,000 to 10,000 times the radiation that would kill a regular human cell. Lead researcher Robert Szabla says Deinococcus also excels in repairing DNA that has already been damaged.
(...)
He says that, in theory, this gene could be introduced into any organism—plants, animals, humans—and it should increase the DNA repair efficiency of that organism's cells.

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https://phys.org/news/2024-08-newly-protein-dna.html

Kommentar: Wäre spannend, wenn das auch beim Menschen funktionieren würde.

Skin Aging and Cellular Mobility at the Protein Level

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The researchers focused on four specific actin-related proteins. CFL1 was substantially decreased in older people, and this protein is also related to wound healing: removing CFL1 from younger fibroblasts sharply increases the amount of time it takes for these cells to engage in healing in vitro. CORO1C was multiplied substantially in older cells, and the researchers were unable to conclude a reason why this was the case: the related mRNA was not very different between younger and older cells. The same was found to be true for another actin-related protein, FLNB.

ARPC3 may be a key part of this puzzle. This protein was found to be necessary for fibroblast migration, and the researchers believe that it regulates CFL1 and CORO1C. They further hold that the combination of the three acts “together to regulate the actin cytoskeleton and the cytoskeleton regulation itself.” This protein is secreted less by aging cells.

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https://www.lifespan.io/news/skin-aging-...-protein-level/

Longevity Effects of Target of Rapamycin and Phosphatidylinositol 3-Kinase Inhibitors and Other Autophagy-Related Supplements in y w Male Drosophila melanogaster
https://www.preprints.org/manuscript/202...KPlZCFDCifbqMxw

Hallo Prometheus,

das ist genau das "Problem": bei Fledermäusen sind z.B. das Reparaturgen in den Zellen, Autophagie sowie die Qualitätskontrolle der Mitochondrien fast dauerhaft aktiviert.

Viele Grüße

Roger

Gene regulation study finds coordination between basic cellular processes is lost with increasing age
https://medicalxpress.com/news/2024-09-g...zWEr9N62LGUQMfg

FOXO-regulated OSER1 reduces oxidative stress and extends lifespan in multiple species

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FOXO transcription factors modulate aging-related pathways and influence longevity in multiple species, but the transcriptional targets that mediate these effects remain largely unknown. Here, we identify an evolutionarily conserved FOXO target gene, Oxidative stress-responsive serine-rich protein 1 (OSER1), whose overexpression extends lifespan in silkworms, nematodes, and flies, while its depletion correspondingly shortens lifespan. In flies, overexpression of OSER1 increases resistance to oxidative stress, starvation, and heat shock, while OSER1-depleted flies are more vulnerable to these stressors. In silkworms, hydrogen peroxide both induces and is scavenged by OSER1 in vitro and in vivo. Knockdown of OSER1 in Caenorhabditis elegans leads to increased ROS production and shorter lifespan, mitochondrial fragmentation, decreased ATP production, and altered transcription of mitochondrial genes. Human proteomic analysis suggests that OSER1 plays roles in oxidative stress response, cellular senescence, and reproduction, which is consistent with the data and suggests that OSER1 could play a role in fertility in silkworms and nematodes. Human studies demonstrate that polymorphic variants in OSER1 are associated with human longevity. In summary, OSER1 is an evolutionarily conserved FOXO-regulated protein that improves resistance to oxidative stress, maintains mitochondrial functional integrity, and increases lifespan in multiple species. Additional studies will clarify the role of OSER1 as a critical effector of healthy aging.

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https://www.nature.com/articles/s41467-024-51542-z

Ob man da jemals eine praktische Anwendung von sehen wird?

Leading cardiologist suggests weight loss drugs like Ozempic may slow aging
https://longevity.technology/news/leadin...slow-aging/amp/

Combination Therapy Works Against Pancreatic Cancer in Mice
https://www.lifespan.io/news/combination...cancer-in-mice/

https://www.scinexx.de/news/medizin/unse...-53-000-knoten/
https://www.embopress.org/doi/full/10.10...318-024-00210-5

Knoten in der DNA, die machen wohl auch irgendwas, daß ich nicht beeinflussen kann und was man nicht weiß. Ob Bier da was bringt?
Bekämpfe Feuer mit Feuer, Nichtwissen mit Nichtwissen?

Hallmarks of regeneration
https://www.cell.com/cell-stem-cell/full...4gysUmHM66fwSA#

Insidious chromatin change with a propensity to exhaust intestinal stem cells during aging

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• Chromatin and gene expression change in intestinal stem cells (ISCs) during aging
• Some changes of chromatin and gene expression have a propensity to exhaust ISCs
• Trithorax-like target genes close their chromatin and decrease expression during aging
• Inhibition of Trithorax-like or its target genes exhausts ISCs during aging

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https://www.cell.com/iscience/fulltext/S2589-0042(24)02018-2

How aging affects stem cells: A fly's tale
https://medicalxpress.com/news/2024-09-a...Sw8rUs_ftj0G35g

Eggs from older mice regain youth when grown in young cells
https://www.nature.com/articles/d41586-024-02872-x

miR-29 is an important driver of aging-related phenotypes

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We show that partial loss of miR-29 extends the lifespan of Zmpste24-/- mice, an established model of progeria, indicating that miR-29 is functionally important in this accelerated aging model. To examine whether miR-29 alone is sufficient to promote aging-related phenotypes, we generated mice in which miR-29 can be conditionally overexpressed (miR-29TG). miR-29 overexpression is sufficient to drive many aging-related phenotypes and led to early lethality. Transcriptomic analysis of both young miR-29TG and old WT mice reveals shared downregulation of genes associated with extracellular matrix organization and fatty acid metabolism, and shared upregulation of genes in pathways linked to inflammation. These results highlight the functional importance of miR-29 in controlling a gene expression program that drives aging-related phenotypes.

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https://www.nature.com/articles/s42003-024-06735-z

TEX264 drives selective autophagy of DNA lesions to promote DNA repair and cell survival

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• Selective autophagy (nucleophagy) repairs nuclear TOP1cc to maintain genome stability
• TEX264 is the nucleophagy receptor for TOP1cc delivery to the lysosomes
• TEX264-orchestrated nucleophagy is ATR- and MRE11-dependent but proteasome independent
• TEX264-TOP1cc axis is evolutionarily conserved and clinically relevant

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https://www.cell.com/cell/fulltext/S0092-8674(24)00911-5

Intercellular nanotube-mediated mitochondrial transfer enhances T cell metabolic fitness and antitumor efficacy

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Mitochondrial loss and dysfunction drive T cell exhaustion, representing major barriers to successful T cell-based immunotherapies. Here, we describe an innovative platform to supply exogenous mitochondria to T cells, overcoming these limitations. We found that bone marrow stromal cells establish nanotubular connections with T cells and leverage these intercellular highways to transplant stromal cell mitochondria into CD8+ T cells. Optimal mitochondrial transfer required Talin 2 on both donor and recipient cells. CD8+ T cells with donated mitochondria displayed enhanced mitochondrial respiration and spare respiratory capacity. When transferred into tumor-bearing hosts, these supercharged T cells expanded more robustly, infiltrated the tumor more efficiently, and exhibited fewer signs of exhaustion compared with T cells that did not take up mitochondria. As a result, mitochondria-boosted CD8+ T cells mediated superior antitumor responses, prolonging animal survival. These findings establish intercellular mitochondrial transfer as a prototype of organelle medicine, opening avenues to next-generation cell therapies.

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https://www.cell.com/cell/fulltext/S0092-8674%2824%2900956-5

Zitat von Prometheus im Beitrag #192

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Diese Plattform ließe sich gut klinisch etablieren, wenn man sie mit einer Leukapherese und anschließender Reinfusion kombiniert!

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The global pattern of centenarians highlights deep problems in demography

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Accurate age data is fundamental to medicine, social sciences, epidemiology, and good government. However, recent and heavily disputed debates on data quality have raised questions on the accuracy of demographic data at older ages. Here, we catalogue late-life survival patterns of every country in the world from 1970-2021 using comprehensive estimates of old-age populations provided by global governments and curated by the United Nations. Analysis of 236 nations or states across 51 years reveals that late-life survival data is dominated by anomalies at all scales and in all time periods. Life expectancy at age 100 and late-life survival from ages 80 to 100+, which we term centenarian attainment rate, is highest in a seemingly random assortment of states. The top 10 ‘blue zone’ regions with the best survival to ages 100+ routinely includes Thailand, Kenya and Malawi – respectively now 212th and 202nd in the world for life expectancy, the non-self-governing territory of Western Sahara, and Puerto Rico where birth certificates are so unreliable they were recently declared invalid as a legal document. These anomalous rankings are conserved across long time periods and multiple non-overlapping cohorts, and do not seem to be sampling effects. Instead these patterns suggest a persistent inability, even for nation-states or global organisations, to detect or measure error rates in human age data, with troubling implications for epidemiology, demography, and medicine.

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https://www.medrxiv.org/content/10.1101/...24313170v1.full

The cell rejuvenation atlas: leveraging network biology to identify master regulators of rejuvenation strategies
https://www.aging-us.com/article/206105/text

Longitudinal changes in epigenetic clocks predict survival in the InCHIANTI cohort
https://www.medrxiv.org/content/10.1101/...veBI_G8kyAOv1BQ

In vivo DNA replication dynamics unveil aging-dependent replication stress
https://www.cell.com/cell/fulltext/S0092...MQODavB5P7EwxLw

c-Jun N-terminal kinase signaling in aging
https://www.frontiersin.org/journals/agi...2i48VIJTwMLiMUw

"Metformin decelerates aging clock in male monkeys"
> https://www.cell.com/cell/abstract/S0092-8674(24)00914-0

Das Diabetesmedikament "Metformin" soll laut einer 40 Monate Studie an Affen die Alterung von Organen, insbesondere des Gehirns, verlangsamen.
Die neuronale Aktivität erinnerte an die von wesentlich jüngeren Affen.

Zitat von Methusalem im Beitrag #199

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"Metformin decelerates aging clock in male monkeys"

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