Integrated Biosciences, a biotechnology company combining synthetic biology and machine learning to target aging, in collaboration with researchers at the Massachusetts Institute of Technology (MIT) and the Broad Institute of MIT and Harvard, today announced results demonstrating the power of artificial intelligence (AI) to discover novel senolytic compounds, a class of small molecules under intense study for their ability to suppress age-related processes such as fibrosis, inflammation and cancer. A new publication authored by company founders in Nature Aging, “Discovering small-molecule senolytics with deep neural networks,” describes the AI-guided screening of more than 800,000 compounds to reveal three drug candidates with comparable efficacy and superior medicinal chemistry properties than those of senolytics currently under investigation.

Senolytics are an emerging class of investigational drug compounds that selectively kill aging-associated senescent cells (left, with red stain) without affecting other cells (right). Using artificial intelligence, researchers from Integrated Biosciences have, for the first time, identified three senolytics with comparable efficacy and superior drug-like properties relative to leading investigational compounds. 

“This research result is a significant milestone for both longevity research and the application of artificial intelligence to drug discovery,” said Felix Wong, Ph.D., co-founder of Integrated Biosciences and first author of the publication. “These data demonstrate that we can explore chemical space in silico and emerge with multiple candidate anti-aging compounds that are more likely to succeed in the clinic, compared to even the most promising examples of their kind being studied today.”

Senolytics are compounds that selectively induce apoptosis, or programmed cell death, in senescent cells that are no longer dividing. A hallmark of aging, senescent cells have been implicated in a broad spectrum of age-related diseases and conditions including cancer, diabetes, cardiovascular disease, and Alzheimer’s disease. Despite promising clinical results, most senolytic compounds identified to date have been hampered by poor bioavailability and adverse side effects. Integrated Biosciences was founded in 2022 to overcome these obstacles, target other neglected hallmarks of aging, and advance anti-aging drug development more generally using artificial intelligence, synthetic biology and other next-generation tools.

“One of the most promising routes to treat age-related diseases is to identify therapeutic interventions that selectively remove these cells from the body similarly to how antibiotics kill bacteria without harming host cells. The compounds we discovered display high selectivity, as well as the favorable medicinal chemistry properties needed to yield a successful drug,” said Satotaka Omori, Ph.D., Head of Aging Biology at Integrated Biosciences and joint first author of the publication. “We believe that the compounds discovered using our platform will have improved prospects in clinical trials and will eventually help restore health to aging individuals.”

Source:  https://www.businesswire.com/

RNA sequencing and gene network data are used to identify candidate genes that could turn back the “transcriptome clock” that reflects the biological age of distinct human cell types.

Technology has the potential to treat major age-related diseases including cardiovascular disease, cardiovascular disease, and cancer. More than 150,000 people die each day across the globe, about two-thirds of them from age-related causes like cancer, neurodegenerative diseases, strokes, and cardiovascular disease. If the process of aging could be slowed or reversed, the incidence of these conditions would be dramatically reduced, and more humans would live longer, healthier lives. However, aging is a complex process involving multiple biological systems – there is no single biomarker for aging. Therefore, developing treatments that target the root causes of aging is very challenging. Ichor is a Validation Project at the Wyss Institute of Harvard that aims to address this problem using high-throughput genetic screening to identify networks of genes that are strongly implicated in aging processes and develop RNA-based therapies that can make old cells young again.

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A fuel cell under the skin that converts blood sugar from the body into electrical energy sounds like science fiction. Yet it works perfectly, as an ETH Zurich research team led by Martin Fussenegger, Professor of Biotechnology and Bioengineering, has shown. In type 1 diabetes, the body does not produce insulin. This means that patients have to obtain the hormone externally to regulate their blood sugar levels. Nowadays, this is mostly done via insulin pumps that are attached directly to the body. These devices, as well as other medical applications such as pacemakers, require a reliable energy supply, which at present is met primarily by power from either single-​use or rechargeable batteries.

Now, a team of researchers led by Martin Fussenegger from the Department of Biosystems Science and Engineering at ETH Zurich in Basel (Switzerland) have put a seemingly futuristic idea into practice. They have developed an implantable fuel cell that uses excess blood sugar (glucose) from tissue to generate electrical energy. The researchers have combined the fuel cell with artificial beta cells developed by their group several years ago. These produce insulin at the touch of a button and effectively lower blood glucose levels much like their natural role models in the pancreas.

“Many people, especially in the Western industrialised nations, consume more carbohydrates than they need in everyday life,” Fussenegger explains. This, he adds, leads to obesity, diabetes and cardiovascular disease. “This gave us the idea of using this excess metabolic energy to produce electricity to power biomedical devices,” he says.

At the heart of the fuel cell is an anode (electrode) made of copper-​based nanoparticles, which Fussenegger’s team created specifically for this application. It consists of copper-​based nanoparticles and splits glucose into gluconic acid and a proton to generate electricity, which sets an electric circuit in motion. Wrapped in a nonwoven fabric and coated with alginate, an algae product approved for medical use, the fuel cell resembles a small tea bag that can be implanted under the skin. The alginate soaks up body fluid and allows glucose to pass from the tissue into the fuel cell within.

Source: https://ethz.ch/

A simple eye test that predicts death from cardiovascular disease has been developed by British scientists. It combines artificial intelligence (AI) with scans of the retina – a membrane at the back of peepers that contains light sensitive cells. The technique could lead to a screening programme – enabling drugs and lifestyle changes to be prescribed decades before symptoms emerge. Lead author Professor Alicja Regina Rudnicka, of St George’s University of London, said the test is inexpensive, accessible and non-invasive. People at risk of stroke, heart attack and other circulatory conditions could undergo RV (artificial intelligence enabled retinal vasculometry) during routine visits to the optician.

Prof Rudnicka said: “It has the potential for reaching a higher proportion of the population in the community because of ‘high street’ availability. “RV offers an alternative predictive biomarker to traditional risk-scores for vascular health – without the need for blood sampling or blood pressure measurement. “It is highly likely to help prolong disease-free status in an ever-aging population with increasing comorbidities, and assist with minimising healthcare costs associated with lifelong vascular diseases.”

An algorithm called QUARTZ was developed based on retinal images from tens of thousands of Britons aged 40 to 69. It focused on the width, area and curvature, or tortuosity, of tiny blood vessels called arterioles and venules. The performance of QUARTZ was compared with the widely used Framingham Risk Scores framework – both separately and jointly.

The health of all the participants was tracked for an average of seven to nine years, during which time there were 327 and 201 circulatory disease deaths among 64,144 UK Biobank and 5,862 EPIC-Norfolk participants respectively. In men, arteriolar and venular width, tortuosity, and width variation emerged as important predictors of death from circulatory disease. In women, arteriolar and venular area and width and venular tortuosity and width variation contributed to risk prediction.

The predictive impact of retinal vasculature on circulatory disease death interacted with smoking, drugs to treat high blood pressure, and previous heart attacks. Overall, these predictive models, based on age, smoking, medical history and retinal vasculature, captured between half and two-thirds of circulatory disease deaths in those most at risk.

Source: https://www.mirror.co.uk/

By the time people with Alzheimer’s disease start exhibiting difficulty remembering and thinking, the disease has been developing in their brains for two decades or more, and their brain tissue already has sustained damage. As the disease progresses, the damage accumulates, and their symptoms worsen.

Researchers at Washington University School of Medicine in St. Louis have found that high levels of a normal protein associated with reduced heart disease also protect against Alzheimer’s-like brain damage – at least in mice. The findings, published in Neuron, suggest that raising levels of the protein — known as low-density lipoprotein receptor (LDL receptor) — could potentially be a way to slow or stop cognitive decline.

The discovery of LDL receptor as a potential therapeutic target for dementia is surprising since the protein is much better known for its role in cholesterol metabolism. Statins and PCSK9 inhibitors, two groups of drugs widely prescribed for cardiovascular disease, work in part by increasing levels of LDL receptor in the liver and some other tissues. It is not known whether they affect LDL receptor levels in the brain.

“There are not yet clearly effective therapies to preserve cognitive function in people with Alzheimer’s disease,” said senior author David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. “We found that increasing LDL receptor in the brain strongly decreases neurodegeneration and protects against brain injury in mice. If you could increase LDL receptor in the brain with a small molecule or other approach, it could be a very attractive treatment strategy.”

The key to the importance of LDL receptor lies in a different protein, APOE, that also is linked to both cholesterol metabolism and Alzheimer’s disease. High cholesterol in the blood is associated with increased risk of Alzheimer’s disease, although the exact nature of the association is unclear.

During the long, slow development of Alzheimer’s disease, plaques of a protein called amyloid gradually accumulate in the brain. After many years, another brain protein called tau starts forming tangles that become detectable just before Alzheimer’s symptoms arise. The tangles are thought to be toxic to neurons, and their spread through the brain foretells the death of brain tissue and cognitive decline. First author Yang Shi, PhD, a postdoctoral researcher, and Holtzman previously showed that APOE drives tau-mediated degeneration in the brain by activating microglia, the brain’s cellular janitorial crew. Once activated, microglia can injure neural tissue in their zeal to clean up molecular debris.

Higher levels of LDL receptor limit the damage APOE can do in part by binding to APOE and degrading it. Higher levels of LDL receptor in the brain, therefore, should pull more APOE out of the fluid surrounding brain cells and mitigate damage even further, the researchers reasoned.

In a recent study, Assistant Professor Feng Lei from the NUS Yong Loo Lin School of Medicine in Singapore shares that drinking tea regularly may improve brain efficiency. It is revealed that regular tea drinkers have better organised brain regions, which is associated with healthy cognitive function, as compared to non-tea drinkers.

By looking at brain imaging data of older adults, individuals who consumed either green tea, oolong tea, or black tea at least four times a week for about 25 years had brain regions that were interconnected in a more efficient way.

“Take the analogy of road traffic as an example – consider brain regions as destinations, while the connections between brain regions are roads. When a road system is better organised, the movement of vehicles and passengers is more efficient and uses less resources. Similarly, when the connections between brain regions are more structured, information processing can be performed more efficiently,” explained Asst Prof Feng.

The results suggests that drinking tea regularly has a protective effect against age-related decline in brain organisation.

Previous studies have also shown that tea intake is beneficial to human health, and the positive effects include mood improvement and cardiovascular disease prevention. Another study led by Asst Prof Feng in 2017 showed that daily consumption of tea can reduce the risk of cognitive decline in older people by 50 per cent.

Asst Prof Feng and his team plan to examine how tea and its bioactive compounds can affect cognitive decline next.

Source: http://nusmedicine.nus.edu.sg

Cardiovascular disease (CVD) is the major cause of death among middle-aged adults around the world; however, in high-income countries deaths from cancer have become twice as frequent as those from CVD.

The findings come from the first large prospective international study documenting the frequency of common diseases and death rates in high-, middle– and low-income countries using a standardized approach. The research, published in The Lancet presented at the European Society of Cardiology Congress, is from the Prospective Urban Rural Epidemiology (PURE) study led by the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences in Hamilton, Canada.

For this paper, the research involved more than 162,500 adults aged 35 to 70 from 21 countries who were followed for a median of 9.5 years.

“The fact that cancer deaths are now twice as frequent as CVD deaths in high-income countries indicates a transition in the predominant causes of death in middle age,” said Salim Yusuf, principal investigator of the study, executive director of PHRI and a professor of medicine at McMaster.

“As CVD declines in many countries because of prevention and treatment, cancer mortality will likely become the leading cause of death globally in the future.

“The high mortality in poorer countries is not due to a higher burden of risk factors, but likely other factors including lower quality and less health care.”

The high-income countries (HIC) in the study were Canada, Saudi Arabia, Sweden and United Arab Emirates. The middle-income countries (MIC) were Argentina, Brazil, Chile, China, Columbia, Iran, Malaysia, Palestine, Philippines, Poland, Turkey and South Africa. The lower-income
countries (LIC) were Bangladesh, India, Pakistan, Tanzania and Zimbabwe.

Source: https://brighterworld.mcmaster.ca

‘In future, it will be possible to diagnose diabetes from the eye using automatic digital retinal screening, without the assistance of an ophthalmologist‘: these were the words used by Ursula Schmidt-Erfurth, Head of MedUni Vienna‘s Department of Ophthalmology and Optometrics. The scientist has opened the press conference about the ART-2018 Specialist Meeting on new developments in retinal therapy. The automatic diabetes screening, has been recently implemented at MedUni Vienna.
Patients flock to the Department to undergo this retinal examination to detect any diabetic changes. It takes just a few minutes and is completely non-invasive

Essentially this technique can detect all stages of diabetic retinal disease – high-resolution digital retinal images with two million pixels are taken and analyzed within seconds – but Big Data offers even more potential: nowadays it is already possible to diagnose an additional 50 other diseases in this way. Diabetes is just the start. And MedUni Vienna is among the global leaders in this digital revolution.

The Division of Cardiology led by Christian Hengstenberg within the Department of Medicine II is working on how digital retinal analysis can also be used in future for the early diagnosis of cardiovascular diseases.

“This AI medicine is ‘super human’,” emphasizes Schmidt-Erfurth. “The algorithms are quicker and more accurate. They can analyze things that an expert cannot detect with the naked eye.” And yet the commitment to Big Data and Artificial Intelligence is not a plea for medicine without doctors, which some experts predict for the not-to-distant future. “What we want are ‘super doctors’, who are able to use the high-tech findings to make the correct, individualized therapeutic decision for their patients, in the spirit of precision medicine, rather than leaving patients on their own.”

However, it is not only in the diagnosis of diseases that Artificial Intelligence and Big Data, plus virtual reality, provide better results. “We are already performing digitized operations with support from Artificial Intelligence. This involves projecting a virtual and precise image of the area of the eye being operated on onto a huge screen – and the surgeon then performs the operation with a perfect view “on screen” as it were, while actually operating on the patient with a scalpel.”

Source: https://www.news-medical.net/

A molecule produced during fasting or calorie restriction has anti-aging effects on the vascular system, which could reduce the occurrence and severity of human diseases related to blood vessels, such as cardiovascular disease, according to a study led by Georgia State University.

“As people become older, they are more susceptible to disease, like cancer, cardiovascular disease and Alzheimer’s disease,” said Dr. Ming-Hui Zou, senior author of the study, director of the Center for Molecular and Translational Medicine at Georgia State. “Age is the most important so-called risk factor for human disease. How to actually delay aging is a major pathway to reducing the incident and severity of human disease. “The most important part of aging is vascular aging. When people become older, the vessels that supply different organs are the most sensitive and more subject to aging damage, so studying vascular aging is very important. This study is focused on vascular aging, and in old age, what kind of changes happen and how to prevent vascular aging.”

In this study, the research team explores the link between calorie restriction (eating less or fasting) and delaying aging, which is unknown and has been poorly studied. The findings are published in the journal Molecular Cell.

The researchers identified an important, small molecule that is produced during fasting or calorie restriction conditions. The molecule, β-Hydroxybutyrate, is one type of a ketone body, or a water-soluble molecule that contains a ketone group and is produced by the liver from fatty acids during periods of low food intake, carbohydrate restrictive diets, starvation and prolonged intense exercise.

Source: https://news.gsu.edu/