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Category: biotech/medical – Page 2,449

Downregulation of the inflammatory network in senescent fibroblasts and aging tissues of the long‐lived and cancer‐resistant subterranean wild rodent, Spalax

The blind mole rat (Spalax) is a wild, long‐lived rodent that has evolved mechanisms to tolerate hypoxia and resist cancer. Previously, we demonstrated high DNA repair capacity and low DNA damage in Spalax fibroblasts following genotoxic stress compared with rats. Since the acquisition of senescence‐associated secretory phenotype (SASP) is a consequence of persistent DNA damage, we investigated whether cellular senescence in Spalax is accompanied by an inflammatory response. Spalax fibroblasts undergo replicative senescence (RS) and etoposide‐induced senescence (EIS), evidenced by an increased activity of senescence‐associated beta‐galactosidase (SA‐β‐Gal), growth arrest, and overexpression of p21, p16, and p53 mRNAs. Yet, unlike mouse and human fibroblasts, RS and EIS Spalax cells showed undetectable or decreased expression of the well‐known SASP factors: interleukin‐6 (IL6), IL8, IL1α, growth‐related oncogene alpha (GROα), SerpinB2, and intercellular adhesion molecule (ICAM‐1). Apparently, due to the efficient DNA repair in Spalax, senescent cells did not accumulate the DNA damage necessary for SASP activation. Conversely, Spalax can maintain DNA integrity during replicative or moderate genotoxic stress and limit pro‐inflammatory secretion. However, exposure to the conditioned medium of breast cancer cells MDA‐MB‐231 resulted in an increase in DNA damage, activation of the nuclear factor κB (NF‐κB) through nuclear translocation, and expression of inflammatory mediators in RS Spalax cells. Evaluation of SASP in aging Spalax brain and intestine confirmed downregulation of inflammatory‐related genes. These findings suggest a natural mechanism for alleviating the inflammatory response during cellular senescence and aging in Spalax, which can prevent age‐related chronic inflammation supporting healthy aging and longevity.

Mice with hyper-long telomeres show less metabolic aging and longer lifespans

Short telomeres trigger age-related pathologies and shorter lifespans in mice and humans. In the past, we generated mouse embryonic (ES) cells with longer telomeres than normal (hyper-long telomeres) in the absence of genetic manipulations, which contributed to all mouse tissues. To address whether hyper-long telomeres have deleterious effects, we generated mice in which 100% of their cells are derived from hyper-long telomere ES cells. We observe that these mice have longer telomeres and less DNA damage with aging. Hyper-long telomere mice are lean and show low cholesterol and LDL levels, as well as improved glucose and insulin tolerance. Hyper-long telomere mice also have less incidence of cancer and an increased longevity. These findings demonstrate that longer telomeres than normal in a given species are not deleterious but instead, show beneficial effects.

The ‘unbelievable journey’ of CRISPR, now on Netflix

Mankind’s ability to edit the fabric of human life has led to scientific upheaval, global debate, and at least one international incident. Now, it’s coming to Netflix.

“Unnatural Selection,” a four-part docuseries debuting Friday, dissects the stories, science, and ethics behind genome editing, following academics, biohackers, and patients as they move through a brave new world made possible by technologies like CRISPR.

We recently spoke with co-directors Joe Egender and Leeor Kaufman about how the series came to be and how it frames the sprawling story of human genetic engineering. This transcript has been lightly edited for clarity.

Kelsey Moody Presenting on the LysoClear Program at Ending Age-Related Diseases 2019

Kelsey Moody of Ichor Therapeutics presented on the LysoClear development program at the Ending Age-Related Diseases conference organized by the Life Extension Advocacy Foundation earlier this year. LysoClear is an example of the commercial development of a rejuvenation therapy, taken all the way from the starting point of the discovery of microbial enzymes capable of breaking down certain forms of harmful age-related molecular waste that contribute to aging and age-related diseases. The actual research is largely done, and the task now is to focus on manufacture, regulatory approval, and entry into the clinic.

Taken end to end, I think that this development program might be able to lay claim to being the first and oldest of the modern rejuvenation research initiatives, starting sometime back in the early 2000s. It began at the Methuselah Foundation as LysoSENS, the first of the SENS programs to get underway with modest philanthropic funding. Some of you may remember gathering dirt from graveyards to send in for analysis, in the hunt for microbial species that consume the molecular waste that our bodies cannot remove. Researches knew that those microbes existed because graveyards do not accumulate this waste — it is being broken down by something in the environment. The program carried forward into the SENS Research Foundation when it spun out from the Methuselah Foundation, and a portion of it was later licensed to Ichor Therapeutics, and became LysoClear.

Kelsey Moody at Ending Age-Related Diseases 2019.

The MitoMouse Project Smashes its Initial Fundraising Goal!

Wonderful news, the MitoMouse project has successfully reached its initial $50k goal and is well on the way towards the first stretch goal! This now means the projecct will launch at the lab and the MitoMouse strain will be created.

The next step for this ambitious project is to actually create progency from the SickMice and MitoMice in order to have an effective model to test the mitochondrial repair approach, which has already been shown to work in cells, in living animals. If successful it would be vindication for mitochondrial repair therapy and move the therapy closer to translation to humans. Here is Dr. Amutha Boominathan, the leader of the MitoMouse Project at the SENS Research Foundation, to tell us a little more about the first stretch goal for the project.

Marijuana: The Super Antibiotic Of The Future

Obama even allotted $1.2 billion to the annual budget for the establishment of a special task force devoted to the issue, one that would develop an action plan for stopping the fast spread of antibiotic resistant bacteria like MRSA.

A Game Changing Study

In 2008, however, a first of its kind study conducted by a team of British and Italian researchers had already found that one of the world’s most commonly cultivated plants could stop MRSA in its tracks: marijuana.

New universe of miniproteins is upending cell biology and genetics

Small proteins also promise to revise the current understanding of the genome. Many appear to be encoded in stretches of DNA—and RNA—that were not thought to help build proteins of any sort. Some researchers speculate that the short stretches of DNA could be newborn genes, on their way to evolving into larger genes that make full-size proteins. Thanks in part to small proteins, “We need to rethink what genes are,” says microbiologist and molecular biologist Gisela Storz of the National Institute of Child Health and Human Development in Bethesda, Maryland.

Tiny proteins help power muscles and provide the toxic punch to many venoms.

Flexible, wearable supercapacitors based on porous nanocarbon nanocomposites

Evening gowns with interwoven LEDs may look extravagant, but the light sources need a constant power supply from devices that are as well wearable, durable, and lightweight. Chinese scientists have manufactured fibrous electrodes for wearable devices that are flexible and excel by their high energy density. Key for the preparation of the electrode material was a microfluidic technology, as shown in the journal Angewandte Chemie.

Dresses emitting sparkling light from hundreds of small LEDs may create eye-catching effects in ballrooms or on fashion shows. But wearable electronics can also mean sensors integrated in functional textiles to monitor, for example, water evaporation or temperature changes. Energy storage systems powering such must combine deformability with high capacity and durability. However, deformable electrodes often fail in long-term operation, and their capacity lags behind that of other state-of-the-art energy storage devices.

Electrode materials usually benefit from a fine balance of porosity, conductivity, and electrochemical activity. Material scientists Su Chen, Guan Wu, and their teams from Nanjing Tech University, China, have looked deeper into the material demands for flexible electrodes and developed a porous hybrid material synthesized from two carbon nanomaterials and a metal-organic framework. The nanocarbons provided the and excellent electrical conductivity, and the metal-organic framework gave the porous structure and the electrochemical activity.

Diabetes: A Next-Generation Therapy Soon Available?

Insulin, a hormone essential for regulating blood sugar and lipids, is normally produced by pancreatic β cells. In many people with diabetes, however, pancreatic cells are not (or no longer) functional, causing a chronic and potentially fatal insulin deficiency that can only be controlled through daily insulin injections. However, this approach has serious adverse effects, including an increased risk of life-threatening hypoglycaemia, and it does not restore metabolic balance. In order to improve therapy, researchers at the University of Geneva (UNIGE), Switzerland, have identified a protein called S100A9 which, under certain conditions, seems to act as a blood sugar and lipid regulator while avoiding the most harmful side effects of insulin. This discovery, that can be read in Nature Communications, paves the way for better treatment of diabetes and could significantly improve the quality of life for tens of millions of people affected by insulin deficiency.

Today, insulin injections are essential for the survival of patients with type 1 diabetes or a severe form of type 2 diabetes. However, this treatment is not without risk: overdose can trigger hypoglycaemia, i.e. a drop in blood glucose levels that can lead to coma or even death. But underdosed, it can lead to equally dangerous hyperglycaemia. In addition, insulin is involved in the control of ketones, elements that are produced when the liver breaks down lipids in the absence of sufficient glucose reserves, which become toxic in too large quantities. In addition, long-term insulin treatments cause excess fat and cholesterol in the blood and therefore increases the risk of cardiovascular disease.

As early as 2010, Roberto Coppari’s team, a professor at the Diabetes Centre of the UNIGE Faculty of Medicine, highlighted the gluco- and lipid-regulatory properties of leptin, a hormone involved in hunger control. “However, leptin has proved difficult to use pharmacologically in human beings due to the development of leptin resistance,” says Roberto Coppari. “In order to overcome this problem, we shifted our focus on the metabolic mechanisms triggered by leptin rather than on the hormone itself.”

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