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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To the general public, it may sound like something out of a science fiction movie: diagnosing serious diseases such as cancer by listening to someone’s voice. But in fact, researchers funded by the National Institutes of Health (NIH) are now investigating whether changes in a person’s voice could serve as a new biomarker in clinical care for detecting illnesses early.

The project, called Voice as a Biomarker of Health, will include 12 research institutions and is being funded by the Bridge to Artificial Intelligence (Bridge2AI) program out of the NIH Common Fund. The project will use machine learning to build a database of vocal biomarkers, and then use the science of acoustic analysis to identify changes—such as pitch, amplitude, cadence, and words per minute—that could become a low-cost diagnostic tool, alongside other clinical tests.

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The onset of Alzheimer’s disease can be diagnosed by examining proteins in the retina instead of complicated and invasive PET scans or cerebrospinal fluid analysis. Alzheimer’s disease – the progressive neurological disorder that causes the brain to shrink and brain cells to die – is the most common cause of dementia. The disease causes a continuous decline in thinking, behavior and social skills that affect a person’s ability to function independently.

But while the disorder is incurable, it is important to diagnose it as rapidly as possible so measures can be taken to slow the decline. Doctors hope to eventually develop treatments to reduce the risk of developing Alzheimer’s disease.

But now, doctors in the ophthalmology department of the Samson Assuta-Ashdod University Hospital suggest a much simpler way to diagnose Alzheimer’s – by looking for beta-amyloid plaques and abnormal tau proteins in the retina of the eye. The advantage is the accessibility of the retina for direct visualization by non-invasive means.

The retina is a component of the central nervous system that can easily be accessed by technology used routinely by ophthalmologists, they wrote. Photoreceptors in this “screen” at the back of the eye absorb light and transfer data to the retinal ganglion cell layer. Axons (long, slender nerve fibers) in this layer accumulate along the retinal nerve fiber layer and transfer the data to the brain via the optic nerve connected to the eye.

Since the retina is connected to the brain, it seems that changes in this part of the eye reflect pathological processes in the brain, the authors wrote, including the development of Alzheimer’s disease. Amyloid-beta plaques have been found in the retina of cadavers in autopsies of people who died of Alzheimer’s.

Turmeric is a natural, intensely yellow-colored spice that attaches itself to plaques of amyloid-beta. Ten Alzheimer’s patients and six healthy controls were asked to swallow turmeric capsules. A few days later, their retinas were examined. The yellow spice was found to stick to the retinal cells in Alzheimer’s patients but not in the healthy controls. Other non-invasive tests of the retina – including optical coherence tomography and optical coherence tomography angiography – were also conducted and found to point to the early development of Alzheimer’s, the authors wrote. Still, larger tests must be conducted with these means before they can be implemented clinically. A clear biomarker must also be found in the individual to be sure the patient is developing Alzheimer’s and sent for treatments, they concluded.

The research, just published in the latest issue of Harefuah – the Hebrew-language journal of the Israel Medical Association – was conducted by Drs. Keren Wood of the Samson Assuta Ashdod Hospital and Ben-Gurion University of the Negev, Idit Maharshak of Wolfson Medical Center in Holon and Tel Aviv University’s Sackler Faculty of Medicine, and Yosef Koronyo and Maya Koranyo-Hamaoui of the Cedars-Sinai Medical Center in Los Angeles, California.

Source: https://www.jpost.com/

A sensor identifies misfolded protein biomarkers in the blood. This offers a chance to detect Alzheimer’s disease before any symptoms occur. Researchers intend to bring it to market maturity. The dementia disorder Alzheimer’s disease has a symptom-free course of 15 to 20 years before the first clinical symptoms emerge. Using an immuno-infrared sensor developed in Bochum (Germany), a research team is able to identify signs of Alzheimer’s disease in the blood up to 17 years before the first clinical symptoms appear. The sensor detects the misfolding of the protein biomarker amyloid-beta. As the disease progresses, this misfolding causes characteristic deposits in the brain, so-called plaques.

“Our goal is to determine the risk of developing Alzheimer’s dementia at a later stage with a simple blood test even before the toxic plaques can form in the brain, in order to ensure that a therapy can be initiated in time,” says Professor Klaus Gerwert, founding director of the Centre for Protein Diagnostics (PRODI) at Ruhr-Universität Bochum (RUB). His team cooperated for the study with a group at the German Cancer Research Centre in Heidelberg (DKFZ) headed by Professor Hermann Brenner.

The team published the results obtained with the immuno-infrared sensor in the journal “Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association” on 19 July 2022. This study is supported by a comparative study published in the same journal on 2 March 2022, in which the researchers used complementary single-molecule array (SIMOA) technology.

The researchers analysed blood plasma from participants in the ESTHER study conducted in Saarland for potential Alzheimer’s biomarkers. The blood samples had been taken between 2000 and 2002 and then frozen. At that time, the test participants were between 50 and 75 years old and hadn’t yet been diagnosed with Alzheimer’s disease. For the current study, 68 participants were selected who had been diagnosed with Alzheimer’s disease during the 17-year follow-up and compared with 240 control subjects without such a diagnosis. The team headed by Klaus Gerwert and Hermann Brenner aimed to find out whether signs of Alzheimer’s disease could already be found in the blood samples at the beginning of the study.

The immuno-infrared sensor was able to identify the 68 test subjects who later developed Alzheimer’s disease with a high degree of test accuracy (0,78 AUC, Area under Curve). For comparison, the researchers examined other biomarkers with the complementary, highly sensitive SIMOA technology – specifically the P-tau181 biomarker, which is currently being proposed as a promising biomarker candidate in various studies.

Blood Test Spots Signs of Alzheimer’s Years Before Symptoms Appear

“Unlike in the clinical phase, however, this marker is not suitable for the early symptom-free phase of Alzheimer’s disease,” as Klaus Gerwert summarises the results of the comparative study. “Surprisingly, we found that the concentration of glial fibre protein (GFAP) can indicate the disease up to 17 years before the clinical phase, even though it does so much less precisely than the immuno-infrared sensor.” Still, by combining amyloid-beta misfolding and GFAP concentration, the researchers were able to further increase the accuracy of the test in the symptom-free stage to 0,83 AUC.

The Bochum researchers hope that an early diagnosis based on the amyloid-beta misfolding could help to apply Alzheimer’s drugs at such an early stage that they have a significantly better effect – for example, the drug Aduhelm, which was recently approved in the USA. “We plan to use the misfolding test to establish a screening method for older people and determine their risk of developing Alzheimer’s dementia,” says Klaus Gerwert. “The vision of our newly founded start-up betaSENSE is that the disease can be stopped in a symptom-free stage before irreversible damage occurs.” Even though the sensor is still in the development phase, the invention has already been patented worldwide. BetaSENSE aims to bring the immuno-infrared sensor to market and have it approved as a diagnostic device so that it can be used in clinical labs.

Source: https://news.rub.de/

Soon, retinal scans may be able to predict heart attacks. New research has found that decreased complexity in the blood vessels at the back of the retina in the human eye is an early biomarker for myocardial infarction.

“For decades, I’ve always lectured that the eye is not just the window to the soul, but the window to the brain and the window to the body as well,” said ophthalmologist Dr. Howard R. Krauss,

Cardiologist Dr. Rigved Tadwalkar, who was not involved in the research, said that the findings were interesting. “[A]lthough we have known that examination of retinal vasculature can produce insights on cardiovascular health, this study contributes to the evidence base that characteristics of the retinal vasculature can be used for individual risk prediction for myocardial infarction,” he said.

“The greatest appeal,” underlined Dr. Krauss, who was also not involved in the study, “is that the photography station may be remote to the clinician, and perhaps, someday, even accessible via a smartphone.”

According to a press release, the project utilized data from the UK Biobank, which contains demographic, epidemiological, clinical, and genotyping data, as well as retinal images, for more than 500,000 individuals. Under demographic data, the data included individuals’ age, sex, smoking habits, systolic blood pressure, and body-mass index (BMI). The researchers identified about 38,000 white-British participants, whose retinas had been scanned and who later had heart attacks. The biobank provided retinal fundus images and genotyping information for these individuals.

At the back of the retina, on either side where it connects to the optic nerve, are two large systems of blood vessels, or vasculature. In a healthy individual, each resembles a tree branch, with similarly complex fractal geometry. For some people, however, this complexity is largely absent, and branching is greatly simplified. In this research, an artificial intelligence (AI) and deep learning model revealed a connection between low retinal vascular complexity and coronary artery disease.

The research was presented on June 12 at the European Society of Human Genetics.

Source: https://www.medicalnewstoday.com/

Using deep learning to predict “retinal age” from images of the internal surface of the back of the eye, an international team of scientists has found that the difference between the biological age of an individual’s retina and that person’s real, chronological age, is linked to their risk of death. This ‘retinal age gap’ could be used as a screening tool, the investigators suggest.

Reporting on development of their deep learning model and research results in the British Journal of Ophthalmology, first author Zhuoting Zhu, PhD, at Guangdong Academy of Medical Sciences, together with colleagues at the Centre for Eye Research Australia, Sun Yat-Sen University, and colleagues in China, Australia, and Germany, concluded that in combination with previous research, their study results add weight to the hypothesis that “… the retina plays an important role in the aging process and is sensitive to the cumulative damages of aging which increase the mortality risk.”

Estimates suggest that the global population aged 60 years and over will reach 2.1 billion in 2050, the authors noted.

“Aging populations place tremendous pressure on healthcare systems.”

But while the risks of illness and death increase with age, these risks vary considerably between different people of the same age, implying that ‘biological aging’ is unique to the individual and may be a better indicator of current and future health. As the authors pointed out, “Chronological age is a major risk factor for frailty, age-related morbidity and mortality. However, there is great variability in health outcomes among individuals with the same chronological age, implying that the rate of aging at an individual level is heterogeneous. Biological age rather than chronological age can better represent health status and the aging process.”

Several tissue, cell, chemical, and imaging-based indicators have been developed to pick up biological aging that is out of step with chronological aging. But these techniques are fraught with ethical/privacy issues as well as often being invasive, expensive, and time consuming, the researchers noted.

Source: https://www.genengnews.com/

Protein deposits in retina and brain appear to parallel possible neurodegeneration, an insight that might lead to easier, quicker detection. Amyloid plaques are protein deposits that collect between brain cells, hindering function and eventually leading to neuronal death. They are considered a hallmark of Alzheimer’s disease (AD), and the focus of multiple investigations designed to reduce or prevent their formation, including the nationwide A4 study.

But amyloid deposits may also occur in the retina of the eye, often in patients clinically diagnosed with AD, suggesting similar pathologies in both organs. In a small, cross-sectional study, a team of researchers, led by scientists at University of California San Diego School of Medicine, compared tests of retinal and brain amyloids in patients from the A4 study and another study (Longitudinal Evaluation of Amyloid Risk and Neurodegeneration) assessing neurodegeneration risk in persons with low levels of amyloid.

Like the proverbial “windows to the soul,” the researchers observed that the presence of retinal spots in the eyes correlated with brain scans showing higher levels of cerebral amyloid. The finding suggests that non-invasive retinal imaging may be useful as a biomarker for detecting early-stage AD risk.

Amyloid deposits tagged by curcumin fluoresce in a retinal scan.

“This was a small initial dataset from the screening visit. It involved eight patients,” said senior author Robert Rissman, PhD, professor of neurosciences at UC San Diego School of Medicine. “But these findings are encouraging because they suggest it may be possible to determine the onset, spread and morphology of AD — a preclinical diagnosis — using retinal imaging, rather than more difficult and costly brain scans. We look forward to seeing the results of additional timepoint retinal scans and the impact of solanezumab (a monoclonal antibody) on retinal imaging. Unfortunately we will need to wait to see and analyze these data when the A4 trial is completed.”

The findings published in the journal Alzheimer’s & Dementia.

https://ucsdnews.ucsd.edu/

Lung cancer spreads to the brain in about one-quarter of patients with an advanced form of the disease. To date, radiation has been the only treatment option, but it comes with toxic side effects. Researchers at Yale Cancer Center (YCC) have found that use of the checkpoint inhibitor pembrolizumab in place of radiation can extend life with very few side effects in this patient population.

The findings, published in The Lancet Oncology, found that patient response depended on the level of the biomarker (PD-L1) expressed in their tumors. Of those that did respond, overall survival at one year was 40% and 34% at two years.

Pembrolizumab monoclonal antibody drug protein.

“Survival in this cohort of patients exceeds the historically documented survival for patients with brain metastasis from non-small cell lung cancer or NSCLC, which is a two-year survival of about 14%,” said the study’s lead investigator Sarah B. Goldberg, M.D., M.P.H., associate professor of medicine (medical oncology) at YCC.

This is the first study to specifically test the benefit of the treatment in a prospective clinical trial of lung cancer patients who had not yet been treated for brain metastasis or whose tumors recurred after radiation. Before this, most clinical trials of a checkpoint immunotherapy drug did not include patients with brain metastasis, but the few that did provided hints of benefit when retrospectively analyzed.

Source: https://news.yale.edu/

Reports show that cancer is the second-highest leading cause of death globally, with the possibility that every one in four to five people in Singapore may develop cancer in their lifetime. A recent study by scientists from Duke-NUS Medical School provides new evidence supporting the presence of a key mechanism behind progression and relapse in cancer. The study, published in Proceedings of the National Academy of Sciences (PNAS), discusses the role of MBNL1 protein as a biomarker for cancer prognosis, which can lead to the development of new treatment strategies for cancer.

Cancer cases have been rising over the years and according to the statistics, the number of people living with cancer will continue to increase. Despite decades of research, cancer treatments are still inefficient and have unacceptable side effects that continue to prompt an urgent need for new approaches to prevention and treatment. Uncovering novel mechanisms associated with cancer would fill current knowledge gaps and help meet this need.

“We discovered a mechanism involving MBNL1 protein that predicts several characteristics of cancer such as progression and relapse,” said Dr Debleena Ray, Senior Research Fellow at Duke-NUS’ Cancer and Stem Cell Biology (CSCB) programme, the lead author of this study. ”We found that MBNL1 protein is present in low amounts in many of the common cancers in the world, including breast, colorectal, stomach, lung and prostate cancers, which when combined account for about 49 per cent of all cancers diagnosed in 2018. This can cause poor overall survival in many of these commonly-occurring cancers.”

The team also found that this mechanism can be reversed by blocking the JNK protein, a well-known target in cancer treatment, in cancer cells with low levels of MBNL1.

“While JNK inhibitors have been tested as a cancer drug previously, currently there are no clinical trials for the same. However, if in the future there is a JNK inhibitor against cancer, MBNL1 could be used as a biomarker to select patients for the treatment,” said Adjunct Associate Professor David Epstein at the Duke-NUS’ CSCB programme and the co-corresponding author of this study.

“Cancer is a global health challenge and Singapore is no exception. This study provides important information about novel targets and biomarkers that are implicated in several major cancers, which could lead to the development of new treatment strategies that can improve the lives of patients,” said Prof Patrick Casey, Senior Vice Dean for Research at Duke-NUS.

Over the next year, the team will be investigating the role of MBNL1 in colorectal cancer and exploring the potential of anti-JNK therapeutic for cancer using antisense technology, a tool that is used for the inhibition of gene expression.

Reference: Debleena Ray, Yu Chye Yun, Muhammad Idris, Shanshan Cheng, Arnoud Boot, Tan Bee Huat Iain, Steven G. Rozen, Patrick Tan and David M. Epstein (2020). A tumor associated splice-isoform of MAP2K7 drives de- differentiation in MBNL1-low cancers via JNK activation. PNAS. Complete research paper available at this link: https://www.pnas.org/content/early/2020/06/25/2002499117

Source: Duke-NUS

Two newly published studies are presenting novel diagnostic techniques to help catch the most aggressive forms of prostate cancer at an early stage. A University of East Anglia study presents an innovative way to measure gene expression in tumor samples and predict disease severity, while an Australian study details a new kind of imaging technique promising to detect metastasized prostate cancer with greater accuracy than ever before.

Two new techniques are designed to detect aggressive forms of prostate cancer and catch it when it metastasizes

“Prostate cancer is the most common cancer in men in the UK,” explains Colin Cooper, lead researcher on a new study from the University of East Anglia. “It usually develops slowly and the majority of cancers will not require treatment in a man’s lifetime. However, doctors struggle to predict which tumors will become aggressive, making it hard to decide on treatment for many men.”

In order to develop a way for doctors to better identify the most aggressive tumors the researchers examined different gene expression patterns in nearly 2,000 prostate tumor samples. Applying a mathematical model called Latent Process Decomposition, the study homed in on a particular pattern of gene expression associated with the most aggressive clinical cases.

The pattern relates to a subtype of cells the team has labeled DESNT, and suggest the more tumor cells in a sample that are of that DESNT subtype, the faster a patient will progress through the disease. The hope is that this can act as a biomarker to stratify prostate cancer patients, identifying those needing more urgent invasive treatments.

“If you have a tumor that is majority DESNT you are more likely to get metastatic disease, in other words it is more likely to spread to other parts of your body,” says Daniel Brewer, co-lead researcher on the project. “This is a much better indication of aggressive disease.”

Identifying when prostate cancer has metastasized is obviously of vital importance in guiding treatment. A team of Australian researchers just published the results of a clinical trial evaluating the efficacy of a new imaging technique developed to provide detailed data on the spread of the disease.

“Around one in three prostate cancer patients will experience a disease relapse after surgery or radiotherapy,” says Declan Murphy, senior author on the new imaging study. “This is partly because current medical imaging techniques often fail to detect when the cancer has spread, which means some men are not given the additional treatments they need.”

Source: https://newatlas.com/