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Adipose tissue retains an epigenetic memory of obesity after weight loss

We termed enhancers that gained (and maintained) H3K4me1 in obesity and WL ‘new enhancers’. Most of these ‘new enhancers’ were also active (that is, marked by H3K27ac) during obesity and/or WL (Fig. 4D). We then annotated the enhancers to their closest gene and performed a GSEA. In agreement with the promoter GSEA above, we found that the ‘new active enhancers’ were related to inflammatory signalling, lysosome activity and extracellular matrix remodelling (Fig. 4e and Extended Data Fig. 9i), indicating a persistent shift of adipocytes towards a more inflammatory and less adipogenic identity. Corroborating these results, Roh et al. had analysed H3K27ac in adipocytes of obese mice and reported impaired identity maintenance during obesity25.

To combine our findings regarding retained translational changes and epigenetic memory, we investigated whether epigenetic mechanisms, such as differentially marked promoters or enhancers, could explain the persistent translational obesity-associated changes after WL. Notably, 57–62% of downregulated and 68–75% of upregulated persistent translational DEGs after WL could be accounted for by one or more of the analysed epigenetic modalities (Fig. 4f). Overall, these results strongly suggest the presence of stable cellular, epigenetic and transcriptional memory in mouse adipocytes that persists after WL.

Dasatinib + Quercetin: Longevity Biohacker Kenneth Scott’s Experience

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Bedbugs Are Stronger Than Ever and Scientists Just Found Out Why

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Ever since then, researchers have marveled at the bedbug’s resilience. No matter what kind of chemical insecticide we throw at it, they manage to survive. This is due in large part to its development of insecticide resistance. Recent research conducted by Hidemasa Bono at Hiroshima University found that a series of genetic mutations explain the bedbug’s resistance to insecticides.

To figure that out, Bono and his team took a peek at the genome of an insecticide-resistant bedbug. They then compared it to bedbug samples collected in 2010 from a hotel in Hiroshima, along with wild bedbugs dating back to the 1950s. They used a technique called long-read sequencing to create nearly free and nearly error-free genomic maps to compare the various bedbugs across time. This allowed them to see several different mutations across the three types of bedbugs.

They found that the bedbug that came from the hotel had 19,895 times more resistance to one of the most common types of insecticide, pyrethroids, than the nonresistant genome. All told, they identified 729 resistant specific mutations. Some of these mutations are related directly to DNA damage response, cell cycle regulation, and insulin metabolism.

Revolutionizing Brain Diagnostics with Light and AI

Summary: A new “molecular lantern” technique allows researchers to monitor molecular changes in the brain non-invasively using a thin light-emitting probe. This innovative tool utilizes Raman spectroscopy to detect chemical changes caused by tumors, injuries, or other pathologies without altering the brain beforehand.

Unlike prior methods requiring genetic modifications, this approach analyzes natural brain tissue with high precision, offering significant potential for diagnosing and studying brain diseases. Future developments aim to integrate artificial intelligence to enhance diagnostic accuracy and explore diverse biomedical applications.

Critical review of aging clocks and factors that may influence the pace of aging

Background and objectives: Aging clocks are computational models designed to measure biological age and aging rate based on age-related markers including epigenetic, proteomic, and immunomic changes, gut and skin microbiota, among others. In this narrative review, we aim to discuss the currently available aging clocks, ranging from epigenetic aging clocks to visual skin aging clocks.

Methods: We performed a literature search on PubMed/MEDLINE databases with keywords including: “aging clock,” “aging,” “biological age,” “chronological age,” “epigenetic,” “proteomic,” “microbiome,” “telomere,” “metabolic,” “inflammation,” “glycomic,” “lifestyle,” “nutrition,” “diet,” “exercise,” “psychosocial,” and “technology.”

Results: Notably, several CpG regions, plasma proteins, inflammatory and immune biomarkers, microbiome shifts, neuroimaging changes, and visual skin aging parameters demonstrated roles in aging and aging clock predictions. Further analysis on the most predictive CpGs and biomarkers is warranted. Limitations of aging clocks include technical noise which may be corrected with additional statistical techniques, and the diversity and applicability of samples utilized.

Foreign DNA ‘sneaks’ past bacterial defenses, aiding antibiotic resistance

A new study by Tel Aviv University reveals how bacterial defense mechanisms can be neutralized, enabling the efficient transfer of genetic material between bacteria. The researchers believe this discovery could pave the way for developing tools to address the antibiotic resistance crisis and promote more effective genetic manipulation methods for medical, industrial, and environmental purposes.

The study was led by Ph.D. student Bruria Samuel from the lab of Prof. David Burstein at the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University’s Wise Faculty of Life Sciences. Other contributors to the research include Dr. Karin Mittelman, Shirly Croitoru, and Maya Ben-Haim from Prof. Burstein’s lab. The findings were published in the journal Nature.

The researchers explain that genetic diversity is essential for the survival and adaptation of different species in response to environmental changes. For humans and many other organisms, sexual reproduction is the primary driver of the genetic diversity required for survival. However, bacteria and other microorganisms lack such a reproduction mechanism.

AI-designed ‘nanocages’ mimic viral behavior for enhanced gene therapy

Researchers have developed an innovative therapeutic platform by mimicking the intricate structures of viruses using artificial intelligence (AI). Their pioneering research was published in Nature on December 18.

Viruses are uniquely designed to encapsulate genetic material within spherical shells, enabling them to replicate and invade host cells, often causing disease. Inspired by these complex structures, researchers have been exploring artificial proteins modeled after viruses.

These “nanocages” mimic viral behavior, effectively delivering therapeutic genes to target cells. However, existing nanocages face significant challenges: their small size restricts the amount of genetic material they can carry, and their simple designs fall short of replicating the multifunctionality of natural viral proteins.

Simple Dietary Supplement Could Supercharge Cancer-Fighting Immune Cells

A dietary supplement may offer a novel way to enhance the effectiveness of CAR T cell therapy, according to a study conducted by researchers at the Perelman School of Medicine and the Abramson Cancer Center at the University of Pennsylvania. Although this method requires validation through clinical trials, early findings—recently presented during a press briefing at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition—suggest a potentially affordable and accessible strategy to improve CAR T cell functionality and cancer-fighting capabilities.

CAR T cell therapy, first developed at Penn Medicine, is a personalized cancer treatment that reprograms a patient’s immune cells to target and destroy cancer cells.

“Thousands of patients with blood cancers have been successfully treated with CAR T cell therapy, but it still doesn’t work for everyone,” said co-lead author Shan Liu, PhD, a postdoctoral fellow who presented the study at ASH. “We took an outside-the-box approach to improve CAR T cell therapy, by targeting T cells through diet rather than further genetic engineering.”

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