Science Sub-journal: Revealing the Keys to Reversing Aging, Bringing the Brain Back to Age!

Recently, the innovative research on "making the brain younger" was published in Science Translational Medicine and introduced in the form of a cover story, revealing a key role of aging affecting cognitive ability: blood-brain barrier.the study was completed in collaboration with scientists from the University of California, Berkeley and Ben Gurion University in Israel, with the support of the National Institutes of Health (r01ns066005, r56ns066005), the seventh Framework Programme of the European Union, the Israeli Science Foundation and the US Israel science foundation.source: guillaelam / Science Source blood brain barrier (BBB) BBB is the boundary between endothelial cells, pericytes and astrocytes, which separates the brain from the systemic circulation and plays a filtering role.once the integrity of blood-brain barrier is lost, it will lead to nervous system diseases, such as Alzheimer's disease (AD), epilepsy and cognitive impairment in aging process.Professor alon Friedman and others invented an innovative magnetic resonance imaging (MRI) technology dynamic contrast enhanced (DCE) imaging to detect BBB.the results showed that nearly 60% of people over the age of 70 had loopholes in this "brain filtration system". Among them, those with severe cognitive impairment, such as Alzheimer's disease, had more serious blood-brain barrier leakage.DOI: 10.1126/ scitranslmed.aaw8954 Once the brain's filtration system leaks, chemicals in the blood that can cause inflammation and cell death enter the brain tissue.Professor Daniela Kaufer and others found that the changes caused by aging in the brain are similar to those caused by trauma.such as albumin, it is usually dissolved in the serum and blocked by the blood-brain barrier. When the blood-brain barrier has leakage, it infiltrates into the aging brain tissue and induces a series of inflammation, thus causing abnormal excitation of the neural circuit.professor Kaufer speculated that the "inflammatory haze" caused by the leakage of blood-brain barrier may be an important reason for affecting aging brain function.to this end, they injected albumin into the brain of young mice by simulating blood-brain barrier leakage.in just a week, the young brain "gets old.".the researchers carried out experiments from gene expression, inflammatory response, recovery ability to induced epilepsy, mortality after epilepsy, and performance in maze. It was found that these young mice injected with albumin were like old mice, thus reappearing the aging process of brain.Dynamic Enhanced MRI (DCE-MRI) scan showed that the blood-brain barrier of human and mouse leaked with aging source: images by alon Friedman and Daniela Kaufer.DOI: 10.1126/ scitranslmed.aaw8283 The results show that when albumin infiltrates into the brain, it will bind to the transforming growth factor - β (TGF - β) receptor of astrocytes, thus causing inflammation, damaging other brain cells and neural circuits, resulting in decreased inhibition, increased neuronal excitability, and a tendency to epileptic seizures.MRI results of severe blood-brain barrier leakage (left) corresponding to EEG results (right) show that typical paroxysmal slow wave EEG activity appears more frequently in AD patients Kauferlab also, when they genetically engineered older mice to knock out TGF - β receptors in their astrocytes, the brains of older mice looked younger.they are as resistant to epilepsy as young mice and learn mazes like mice. these two papers provide two biomarkers: leakage barrier detected by MRI, abnormal brain rhythm detected by EEG, which can be used to mark people with blood-brain barrier problems, and a potential drug to delay or reverse the consequences. alon Friedman and Daniela Kaufer are co authors of the two studies. They have worked together for more than 20 years, focusing on the role of blood-brain barrier in brain diseases. Source: UC "MRI and EEG are two biomarkers that can accurately show where the blood-brain barrier is leaking, so doctors can identify patients who need treatment and determine the time of administration. They can also track the patient's condition, and when the blood-brain barrier is cured, there is no need to give drugs. Unfortunately, in Palo Alto, California, medical chemist Barry Hart has provided a small molecule drug IPW, which specifically blocks the TGF - β receptor in astrocytes and can cross the blood-brain barrier. the researchers gave the drug to old mice, and the results were very gratifying. The brains of the old mice looked younger.  Kaufer, Friedman and Hart have formed a company to develop a drug to cure the blood-brain barrier for clinical treatment, and hope that the drug will help reduce brain inflammation after stroke, concussion or traumatic brain injury, thereby reducing permanent damage and ultimately preventing brain barrier leakage in elderly people with dementia or Alzheimer's disease. end References: [1] Vladimir v. senatorov Jr. et al., (2019) blood brain barrier dysfunction in aging causes hyper activation of TGF - β signaling and chronic yet reversible neural dysfunction. Science Translational Medicine. [2] Dan Z. milikovsky et al, (2019) Paroxysmalslow cortical activity in Alzheimer’s disease and epilepsy is associated withblood-brain barrier dysfunction. Science Translational Medicine. [3]