Lifeboat Foundation

Excessive fear is a hallmark of anxiety disorders, a major cause of disease burden worldwide. Substantial evidence supports a role of prefrontal cortex-amygdala circuits in the regulation of fear and anxiety, but the molecular mechanisms that regulate their activity remain poorly understood. Here, we show that downregulation of the histone methyltransferase PRDM2 in the dorsomedial prefrontal cortex enhances fear expression by modulating fear memory consolidation. We further show that Prdm2 knock-down (KD) in neurons that project from the dorsomedial prefrontal cortex to the basolateral amygdala (dmPFC-BLA) promotes increased fear expression. Prdm2 KD in the dmPFC-BLA circuit also resulted in increased expression of genes involved in synaptogenesis, suggesting that Prdm2 KD modulates consolidation of conditioned fear by modifying synaptic strength at dmPFC-BLA projection targets.

Loss of epigenetic information can drive aging, restoration can reverse it.

Sources:

Continue reading “How to Reverse Aging? David Sinclair — Epigenetic Information” »

Aging is characterized by changes in cellular identity and function over time. This process is driven by changes in chromatin factor localization during DNA break repair, which alters the epigenome and advances the epigenetic clock. Expression of a subset of Yamanka factors, OSK, can reverse these changes and modulate aging.

When genes are activated and expressed, they show patterns in cells that are similar in type and function across tissues and organs. Discovering these patterns improves our understanding of cells—which has implications for unveiling disease mechanisms.

The advent of spatial transcriptomics technologies has allowed researchers to observe gene expression in their spatial context across entire tissue samples. But new computational methods are needed to make sense of this data and help identify and understand these gene expression patterns.

A research team led by Jian Ma, the Ray and Stephanie Lane Professor of Computational Biology in Carnegie Mellon University’s School of Computer Science, has developed a machine learning tool to fill this gap. Their paper on the method, called SPICEMIX, appeared as the cover story in the most recent issue of Nature Genetics.

The rebooting came in the form of a gene therapy involving three genes that instruct cells to reprogram themselves—in the case of the mice, the instructions guided the cells to restart the epigenetic changes that defined their identity as, for example, kidney and skin cells, two cell types that are prone to the effects of aging. These genes came from the suite of so-called Yamanaka stem cells factors—a set of four genes that Nobel scientist Shinya Yamanaka in 2006 discovered can turn back the clock on adult cells to their embryonic, stem cell state so they can start their development, or differentiation process, all over again. Sinclair didn’t want to completely erase the cells’ epigenetic history, just reboot it enough to reset the epigenetic instructions. Using three of the four factors turned back the clock about 57%, enough to make the mice youthful again.

“We’re not making stem cells, but turning back the clock so they can regain their identity,” says Sinclair. “I’ve been really surprised by how universally it works. We haven’t found a cell type yet that we can’t age forward and backward.”

Rejuvenating cells in mice is one thing, but will the process work in humans? That’s Sinclair’s next step, and his team is already testing the system in non-human primates. The researchers are attaching a biological switch that would allow them to turn the clock on and off by tying the activation of the reprogramming genes to an antibiotic, doxycycline. Giving the animals doxycycline would start reversing the clock, and stopping the drug would halt the process. Sinclair is currently lab-testing the system with human neurons, skin, and fibroblast cells, which contribute to connective tissue.

San Diego-based biotech startup Rejuvenate Bio is making a major claim that’ll likely draw heated scrutiny from the scientific community: that its technology was able to significantly extend the lives of elderly mice.

According to a yet-to-be-peer-reviewed paper, scientists at the company say an injection that reprograms genes in the bodies of senior mice effectively doubled their remaining life span, MIT Technology Review reports.

In tests, the company found that treated mice lived on for another 18 weeks on average. Those who were not treated in a control group only lived for another nine weeks. Overall, they say, the gene hacked mice lived roughly seven percent longer overall.

An international study 13 years in the making demonstrates for the first time that degradation in the way DNA is organized and regulated — known as epigenetics — can drive aging in an organism, independently of changes to the genetic code itself.

The result is a widely anticipated landmark for rejuvenation technology.

Summary: Researchers identify the role the Pig-Q gene plays in sleep regulation. Mutations of the Pig-Q gene increase sleep.

Source: Texas A&M

A research effort involving researchers from Texas A&M University, the Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP) has used human genomics to identify a new genetic pathway involved in regulating sleep from fruit flies to humans—a novel insight that could pave the way for new treatments for insomnia and other sleep-related disorders.