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Category: biotech/medical

Genetics of Aging and Life Span: Molecular Mechanisms and Intervention Prospects

Abstract The review examines modern advances in the genetics of aging and life span. The key molecular mechanisms regulating aging processes at the genetic level are analyzed, including signaling pathways and longevity genes identified in studies on model organisms and through genome analysis of long-lived species. Special attention is given to the insulin/IGF-1 signaling pathway, the role of the FOXO transcription factor, DNA repair systems, epigenetic regulation, and modulation of mTOR and AMPK kinase activity. Results of experimental studies on increasing the life span of model organisms through genetic manipulations and combined approaches are presented.

Man unexpectedly cured of HIV after stem cell transplant

A man has become the seventh person to be left HIV-free after receiving a stem cell transplant to treat blood cancer. Significantly, he is also the second of the seven who received stem cells that were not actually resistant to the virus, strengthening the case that HIV-resistant cells may not be necessary for an HIV cure.

“Seeing that a cure is possible without this resistance gives us more options for curing HIV,” says Christian Gaebler at the Free University of Berlin.

Image: STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY

A handful of people with HIV have been cured after receiving HIV-resistant stem cells – but a man who received non-resistant stem cells is also now HIV-free.

By Carissa Wong

Scientists Discover a Way to ‘Recharge’ Aging Human Cells

New research shows how human cells can be effectively ‘recharged’ by replacing their internal batteries – microscopic power stations called mitochondria – and the discovery could have wide-ranging benefits across healthcare and medical treatments.

The stacks of mitochondria in most of our cells naturally decline in numbers, slow down, and wear out with age. Once they start operating below peak capacity, they can contribute to multiple diseases everywhere from the heart to the brain.

In this latest study, researchers from Texas A&M University used special flower-shaped particles called nanoflowers to scavenge damaging oxygen molecules, triggering genes that increase the number of mitochondria in human stem cells.

Epigenetic changes regulate gene expression, but what regulates epigenetics?

A chromosome pulled from the flowers of Arabidopsis thaliana (green and white) unspools to reveal DNA (blue) coiled around packaging-proteins called histones (purple). The direction of epigenetic changes by genetic features begins as the RIM transcription factor (pink) docks on a corresponding DNA sequence (pink). Once docked, the RIM transcription factor directs methylation machinery to tack methyl groups (orange) onto specific nearby cytosines (orange). Click here for a high-resolution image. Credit: Salk Institute.

All the cells in an organism have the exact same genetic sequence. What differs across cell types is their epigenetics—meticulously placed chemical tags that influence which genes are expressed in each cell. Mistakes or failures in epigenetic regulation can lead to severe developmental defects in plants and animals alike. This creates a puzzling question: If epigenetic changes regulate our genetics, what is regulating them?

Scientists at the Salk Institute have now used plant cells to discover that a type of epigenetic tag, called DNA methylation, can be regulated by genetic mechanisms. This new mode of plant DNA methylation targeting uses specific DNA sequences to tell the methylation machinery where to dock. Prior to this study, scientists had understood only how DNA methylation was regulated by other epigenetic features, so the discovery that genetic features can also guide DNA methylation patterns is a major paradigm shift.

Digital twins for in vivo metabolic flux estimations in patients with brain cancer

Quantifying metabolic activity in patient tumors could advance personalized cancer targeting. Meghdadi et al. develop a digital twin framework using machine learning to quantify metabolic fluxes in tissues from patients with glioma, identifying which patients may benefit from different targeted metabolic therapies like specialized diets or pharmacologic agents.

Beyond the Buzz: Tumor Treating Fields for Cancer

Tumor-treating fields (TTFields) are gaining traction as evidence expands beyond early enthusiasm, Medscape reports. Once considered experimental, TTFields are now supported by multiple randomized trials and are being tested across a growing list of solid tumors, positioning the therapy as a potential addition to standard cancer care in selected patients.

Here’s a look at how it works, the body of evidence, and the limitations.

Tumor treating fields use low intensity, alternating electric fields to disrupt cancer cell division.

The electric fields are generated by a wearable device — Optune Gio for glioblastoma and Optune Lua for pleural mesothelioma and NSCLC — developed and marketed by Switzerland-based oncology company Novocure.

Study probes ‘covert consciousness’

Ricardo Iriart last saw his wife conscious four years ago. Every day since, he has visited Ángeles, often spending hours talking to her in hopes that she could hear him.

Over the last year, he’s gotten a new understanding of his wife’s condition, participating in cutting-edge research into “covert consciousness.” It’s an emerging field of study that probes what patients with disorders of consciousness can comprehend, even when they can’t respond.

Earlier this year, the University of Pittsburgh became the first research institution in the U.S. to use an Austrian device called the mindBeagle in a clinical trial of covert consciousness.

Rebalancing viral and immune damage versus repair prevents death from lethal influenza infection

Recovery from deadly influenza infection may hinge on helping the lungs heal in addition to stopping the virus, according to a new Science study in mice.

The results show that pairing modest antiviral therapies with immune modulation can restore damaged tissues and lung function, even after severe infection has taken hold.

Maintaining tissue function while eliminating infected cells is fundamental, and inflammatory damage plays a major contribution to lethality after lung infection. We tested 50 immunomodulatory regimes to determine their ability to protect mice from lethal infection. Only neutrophil depletion soon after infection prevented death from influenza. This result suggests that the infected host passed an early tipping point after which limiting innate damage alone could not rescue lung function. We investigated treatments that could have efficacy when administered later in infection. We found that partial limitation of viral spread together with enhancement of epithelial repair, by interferon blockade or limiting CD8+ T cell–mediated killing of epithelial cells, reduced lethality.

Tooth–bone attachment tissue is produced by cells with a mixture of odontoblastic and osteoblastic features in reptiles

Several types of tooth–bone attachment have evolved in different branches of amniotes. The most studied type of tooth anchorage is thecodont implantation, characterized by a nonmineralized periodontal ligament linking the tooth to the jawbone inside a deep alveolus (Bertin et al., 2018 ; Diekwisch, 2001). This attachment, called gomphosis, is present in mammals and crocodilians and provides robust resistance to mechanical stress during food processing (McIntosh et al., 2002).

By contrast, the teeth of recent lepidosaurian reptiles are firmly attached to the jaw bones, although the morphology of this type of attachment varies across species (Gaengler, 2000). In most lizards and snakes, teeth are ankylosed to the inner side of the high labial wall of the jawbone (pleurodont attachment). However, in some species (e.g., agamas, chameleons), the teeth are completely fused to the crest of the tooth-bearing bone (acrodont teeth) (Edmund, 1960). Such cases, where the teeth are firmly fused to the tooth-bearing element by mineralized tissue, are called ankylosis (for nomenclature, see a recent review by Bertin et al., 2018). Although ankylosis is widespread in nature, in mammals, a fusion of the tooth to the bone by hard tissue is considered a pathological condition (Palone et al., 2020 ; Tong et al., 2020).

Diverse developmental mechanisms have been proposed to explain the evolutionary origin and elaboration of ankylosis. The first developmental step of ankylosis is described as a soft ligament mineralization (LeBlanc et al., 2016 ; Liu et al., 2016). The periodontal ligaments in ancestral mammals have been predicted to display a high osteogenic potential, with an inclination to become calcified, thus resulting in dental ankylosis (LeBlanc et al., 2016). The mineralized ligamentous tissue has been preserved in fossilized mosasaurs, and it is also evident in several fish species and modern snakes (LeBlanc, Lamoureux, & Caldwell, 2017 ; Luan et al., 2009 ; Peyer, 1968). In the second type, ankylosis has been described as developing without ligament formation, with the tooth base firmly attached directly to the top of the tooth-bearing bony pedicles with no sign of previous ligament production (Buchtová et al., 2013 ; Luan et al., 2009).

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